{"id":"durvalumab","rwe":[{"pmid":"41904890","year":"2026","title":"MVI-targeted carbon-ion radiotherapy combined with immunotherapy for advanced hepatocellular carcinoma: Phase Ib DEPARTURE trial.","finding":"","journal":"JHEP reports : innovation in hepatology","studyType":"Clinical Study"},{"pmid":"41904053","year":"2026","title":"Brief Report: Treatment Patterns and Outcomes in a Large Real-World Cohort of Patients With ES-SCLC Treated With First-Line Chemoimmunotherapy in the United States.","finding":"","journal":"Clinical lung cancer","studyType":"Clinical Study"},{"pmid":"41902997","year":"2026","title":"The logarithmic phase as a therapeutic direction: evaluating pharmacological strategies against cancer progression.","finding":"","journal":"Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico","studyType":"Clinical Study"},{"pmid":"41899644","year":"2026","title":"A Real-World, Single-Center, Observational Retrospective Experience of Durvalumab Treatment After Concomitant Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer.","finding":"","journal":"Cancers","studyType":"Clinical Study"},{"pmid":"41899291","year":"2026","title":"Prognostic Impact and Postoperative Management Following Poor Pathological Response to Perioperative FLOT in Resectable Gastric and GEJ Adenocarcinoma: A Systematic Review and Meta-Analysis.","finding":"","journal":"Journal of clinical medicine","studyType":"Clinical Study"}],"_fda":{"id":"686baf25-364f-4124-858f-151f1dae3756","set_id":"8baba4ea-2855-42fa-9bd9-5a7548d4cec3","openfda":{"nui":["N0000193338","N0000193337","N0000193336","M0001357"],"unii":["28X28X9OKV"],"route":["INTRAVENOUS"],"rxcui":["1919507","1919512","1919515","1919516"],"spl_id":["686baf25-364f-4124-858f-151f1dae3756"],"brand_name":["IMFINZI"],"spl_set_id":["8baba4ea-2855-42fa-9bd9-5a7548d4cec3"],"package_ndc":["0310-4500-12","0310-4611-50"],"product_ndc":["0310-4500","0310-4611"],"generic_name":["DURVALUMAB"],"product_type":["HUMAN PRESCRIPTION DRUG"],"pharm_class_cs":["Antibodies, Monoclonal [CS]"],"substance_name":["DURVALUMAB"],"pharm_class_epc":["Programmed Death Ligand-1 Blocker [EPC]"],"pharm_class_moa":["Programmed Death Ligand-1 Antagonists [MoA]","Programmed Death Ligand-1-directed Antibody Interactions [MoA]"],"manufacturer_name":["AstraZeneca Pharmaceuticals LP"],"application_number":["BLA761069"],"is_original_packager":[true]},"version":"32","pregnancy":["8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, IMFINZI can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of IMFINZI in pregnant women. In animal reproduction studies, administration of durvalumab to pregnant cynomolgus monkeys from the confirmation of pregnancy through delivery at exposure levels approximately 6 to 20 times higher than those observed at the clinical dose of 10 mg/kg based on area under the curve (AUC), resulted in an increase in premature delivery, fetal loss, and premature neonatal death ( see Data ). Human immunoglobulin G1 (IgG1) is known to cross the placental barrier; therefore, durvalumab has the potential to be transmitted from the mother to the developing fetus. Apprise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data As reported in the literature, the PD-1/PD-L1 pathway plays a central role in preserving pregnancy by maintaining maternal immune tolerance to the fetus. In mouse allogeneic pregnancy models, disruption of PD-L1 signaling was shown to result in an increase in fetal loss. The effects of durvalumab on prenatal and postnatal development were evaluated in reproduction studies in cynomolgus monkeys. Durvalumab was administered from the confirmation of pregnancy through delivery at exposure levels approximately 6 to 20 times higher than those observed at a clinical dose of 10 mg/kg (based on AUC). Administration of durvalumab resulted in premature delivery, fetal loss (abortion and stillbirth), and increase in neonatal deaths. Durvalumab was detected in infant serum on postpartum Day 1, indicating the presence of placental transfer of durvalumab. Based on its mechanism of action, fetal exposure to durvalumab may increase the risk of developing immune-mediated disorders or altering the normal immune response and immune-mediated disorders have been reported in PD-1 knockout mice."],"description":["11 DESCRIPTION Durvalumab is a programmed cell death ligand 1 (PD-L1) blocking antibody. Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that is produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cell suspension culture. IMFINZI (durvalumab) Injection for intravenous use is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow solution, free from visible particles. Each 500 mg vial of IMFINZI contains 500 mg of durvalumab in 10 mL solution. Each mL contains durvalumab, 50 mg, L-histidine (2 mg), L-histidine hydrochloride monohydrate (2.7 mg), α,α-trehalose dihydrate (104 mg), Polysorbate 80 (0.2 mg), and Water for Injection, USP. Each 120 mg vial of IMFINZI contains 120 mg of durvalumab in 2.4 mL solution. Each mL contains durvalumab, 50 mg, L-histidine (2 mg), L-histidine hydrochloride monohydrate (2.7 mg), α,α-trehalose dihydrate (104 mg), Polysorbate 80 (0.2 mg), and Water for Injection, USP."],"how_supplied":["16 HOW SUPPLIED/STORAGE AND HANDLING IMFINZI (durvalumab) Injection is a clear to opalescent, colorless to slightly yellow solution supplied in a carton containing one single-dose vial either as: • 500 mg/10 mL (50 mg/mL) (NDC 0310-4611-50) • 120 mg/2.4 mL (50 mg/mL) (NDC 0310-4500-12) Store in a refrigerator at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze. Do not shake."],"geriatric_use":["8.5 Geriatric Use Of the 401 patients with resectable NSCLC treated with IMFINZI in combination with chemotherapy in the AEGEAN study, 209 (52%) patients were 65 years or older and 49 (12%) patients were 75 years or older. There were no overall clinically meaningful differences in safety or efficacy between patients ≥ 65 years of age and younger patients. Of the 476 patients with unresectable, Stage III NSCLC treated with IMFINZI in the PACIFIC study, 45% were 65 years or older, while 7.6% were 75 years or older. No overall differences in safety or effectiveness were observed between patients 65 years or older and younger patients. The PACIFIC study did not include sufficient numbers of patients aged 75 years and over to determine whether they respond differently from younger patients. Of the 330 patients with metastatic NSCLC treated with IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy, 143 (43%) patients were 65 years or older and 35 (11%) patients were 75 years or older. There were no clinically meaningful differences in safety or efficacy between patients 65 years or older and younger patients. Of the 262 patients with LS-SCLC treated with IMFINZI, 103 (39%) patients were 65 years or older and 15 (6%) patients were 75 years or older. There were no clinically meaningful differences in safety and efficacy between patients 65 years or older and younger patients. Of the 265 patients with ES-SCLC treated with IMFINZI in combination with chemotherapy 101 (38%) patients were 65 years or older and 19 (7.2%) patients were 75 years or older. There were no clinically meaningful differences in safety or efficacy between patients 65 years or older and younger patients. Of the 338 patients with BTC treated with IMFINZI in combination with chemotherapy in the TOPAZ-1 study, 158 (47%) patients were 65 years or older and 38 (11%) patients were 75 years or older. No overall differences in safety or effectiveness of IMFINZI have been observed between patients 65 years of age and older and younger adult patients. Of the 393 patients with uHCC treated with IMFINZI in combination with tremelimumab-actl, 50% of patients were 65 years of age or older and 13% of patients were 75 years of age or older. No overall differences in safety or effectiveness of IMFINZI have been observed between patients 65 years of age and older and younger adult patients. Of the 235 patients with endometrial cancer treated with IMFINZI with carboplatin and paclitaxel, 49% of patients were 65 years of age or older and 12% of patients were 75 years of age or older. No overall differences in safety or effectiveness of IMFINZI have been observed between patients 65 years of age and older and younger adult patients. Of the 530 patients with MIBC treated with IMFINZI in combination with gemcitabine and cisplatin in the NIAGARA study, 272 (51%) patients were 65 years or older, and 57 (11%) patients were 75 years or older. No overall differences in safety or effectiveness of IMFINZI have been observed between patients 65 years of age and older and younger adult patients. Of the 475 patients with resectable GC/GEJC treated with IMFINZI in combination with FLOT chemotherapy in the MATTERHORN study, 184 (39%) patients were 65 years or older and 37 (8%) patients were 75 years or older. No overall differences in safety or effectiveness were observed between patients ≥ 65 years of age and younger adult patients."],"pediatric_use":["8.4 Pediatric Use The safety and effectiveness of IMFINZI have not been established in pediatric patients. Safety and efficacy were assessed but not established in a multi-center, open-label study (NCT03837899) in 45 pediatric patients aged 1 to < 17 years with advanced solid tumors. All 45 patients received at least a single dose of IMFINZI, and 41 patients received IMFINZI in combination with tremelimumab-actl. No new safety signals were observed in pediatric patients in this study. Durvalumab systemic exposure in pediatric patients weighing ≥ 35 kg was within the range of values previously observed in adults given the same weight-based dose, whereas the systemic exposure in pediatric patients weighing < 35 kg was lower than that observed in adults."],"effective_time":"20251125","clinical_studies":["14 CLINICAL STUDIES 14.1 Non-Small Cell Lung Cancer (NSCLC) Neoadjuvant and Adjuvant Treatment of Resectable NSCLC – AEGEAN Study The efficacy of IMFINZI in combination with neoadjuvant chemotherapy, followed by surgery and continued adjuvant treatment with IMFINZI as a single agent was investigated in AEGEAN (NCT03800134), a randomized, double-blind, placebo-controlled, multicenter trial conducted in 802 patients with previously untreated and resectable squamous or non-squamous NSCLC (Stage IIA to select Stage IIIB [AJCC, 8th edition]). Patients were enrolled regardless of tumor PD-L1 expression. Eligible patients had no prior exposure to immune-mediated therapy, a WHO/ECOG Performance status of 0 or 1, and at least one RECIST 1.1 target lesion. Patients with active or prior documented autoimmune disease, or use of any immunosuppressive medication within 14 days of the first dose of IMFINZI were ineligible. The population for efficacy analyses was a modified intent-to-treat [mITT] which excluded patients with known EGFR mutations or ALK rearrangements. Crossover between the study arms was not permitted. Randomization was stratified by disease stage (Stage II vs. Stage III) and by PD-L1 expression (TC < 1% vs. TC ≥ 1%) status. Patients were randomized 1:1 to one of the following treatment arms: • Arm 1: Neoadjuvant IMFINZI 1,500 mg once every 3 weeks for up to 4 cycles in combination with: Squamous tumor histology: carboplatin AUC 6 and paclitaxel 200 mg/m 2 on Day1 of each 3-week cycle, OR cisplatin 75 mg/m 2 on Day 1 and gemcitabine 1250 mg/m 2 on Day 1 and Day 8 of each 3-week cycle, for 4 cycles Non-squamous tumor histology: pemetrexed 500 mg/m 2 and cisplatin 75 mg/m 2 on Day 1 of each 3-week cycle, for 4 cycles OR pemetrexed 500 mg/m 2 and carboplatin AUC 5 on Day 1 of each 3-week cycle, for 4 cycles. Followed by adjuvant IMFINZI 1,500 mg as a single agent for up to 12 cycles post-surgery. • Arm 2: Neoadjuvant placebo in combination with 4 cycles of chemotherapy (see above) prior to surgery. • Followed by placebo for up to 12 cycles post-surgery. All study medications were administered via intravenous infusion. In the event of unfavorable tolerability, patients who met the eligibility criteria were switched from cisplatin to carboplatin therapy at any point during the study. In patients with comorbidities or unable to tolerate cisplatin as per Investigators judgment, carboplatin AUC 5 could be administered from cycle 1. Treatment with IMFINZI or placebo continued until completion of the treatment, disease progression that precluded definitive surgery, inability to complete definitive surgery, disease recurrence in the adjuvant phase, or unacceptable toxicity. A RECIST 1.1 tumor assessment was performed at baseline, and upon completion of the neoadjuvant period (prior to surgery). Tumor assessments were conducted at 5 weeks postoperatively, prior to the start of adjuvant therapy and every 12 weeks until week 48, every 24 weeks for approximately 4 years, and then every 48 weeks thereafter until disease progression, consent withdrawal, or death. The trial was not designed to isolate the effect of IMFINZI in each phase (neoadjuvant or adjuvant) of treatment. The major efficacy outcome measures of the study were pathological complete response (pCR) by blinded central pathology review and event-free survival (EFS) by blinded independent central review (BICR) assessment. Additional efficacy outcome measures were major pathological response (MPR) by blinded central pathology review, DFS by BICR, and OS. The demographics and baseline disease characteristics were as follows: male (72%); median age 65 years (range: 30 to 88); age ≥ 65 years (52%); WHO/ECOG PS 0 (68%), WHO/ECOG PS 1 (32); White (54%), Asian (41%), Black or African American (0.9%), American Indian or Alaska Native (1.4%), Other Race (2.6%); Not Hispanic or Latino (84%); current or past smokers (86%); squamous histology (49%) and non-squamous histology (51%); Stage II (28%), Stage III (71%); PD-L1 expression status TC ≥ 1% (67%), PD-L1 expression status TC < 1% (33%). In the mITT population, 78% of patients in Arm 1 completed definitive surgery compared to 77% of patients in Arm 2. The trial demonstrated statistically significant improvements in EFS and pCR rate (see Table 26 and Figure 1) in the IMFINZI in combination with chemotherapy arm compared to the placebo in combination with chemotherapy arm. Table 26. Efficacy Results for the AEGEAN Study (mITT) IMFINZI 1,500 mg every 3 weeks with chemotherapy/ IMFINZI (N = 366) Placebo with Chemotherapy/ Placebo (N = 374) EFS Results are based on planned EFS interim analysis and pCR final analysis (DCO: 10 November 2022) which occurred 46.3 months after study initiation. Number of events, n (%) 98 (27) 138 (37) Median EFS (95% CI) (months) NR (31.9, NR) 25.9 (18.9, NR) Hazard ratio (95% CI) 0.68 (0.53, 0.88) 2-sided p-value Compared to a two-sided p-value boundary of 0.00989. The 2-sided p-value for pCR was calculated based on a stratified CMH test. The 2-sided p-value for EFS was calculated based on based on a stratified log-rank test. Stratification factors include PD-L1 and disease stage. 0.0039 pCR , Based on a pre-specified pCR interim analysis (DCO: 14 January 2022) in n = 402, the pCR rate was statistically significant (p = 0.000036) compared to significance level of 0.0082%. , Number of patients with response 63 16 pCR rate, % (95% CI) 17.2 (13.5, 21.5) 4.3 (2.5, 6.8) p-value < 0.0001 Difference in proportions, % (95% CI) Confidence interval for the difference in proportions was calculated based on stratified Miettinen and Nurminen method. 13.0 (8.7, 17.6) Figure 1. Kaplan-Meier Curves of EFS in the AEGEAN Study At the interim analysis, the trial demonstrated a statistically significant difference in MPR rate (34% vs. 14%; p < 0.0001). At the time of the prespecified interim analyses, overall survival (OS) was not formally tested for statistical significance. Unresectable Stage III NSCLC - PACIFIC The efficacy of IMFINZI was evaluated in the PACIFIC study (NCT02125461), a multicenter, randomized, double-blind, placebo-controlled study in patients with unresectable Stage III NSCLC who completed at least 2 cycles of concurrent platinum-based chemotherapy and definitive radiation within 42 days prior to initiation of the study drug and had a WHO performance status of 0 or 1. The study excluded patients who had progressed following concurrent chemoradiation, patients with active or prior documented autoimmune disease within 2 years of initiation of the study or patients with medical conditions that required systemic immunosuppression. Randomization was stratified by sex, age (< 65 years vs. ≥ 65 years), and smoking history (smoker vs. non-smoker). Patients were randomized 2:1 to receive IMFINZI 10 mg/kg or placebo intravenously every 2 weeks for up to 12 months or until unacceptable toxicity or confirmed RECIST v1.1-defined progression. Assessment of tumor status was performed every 8 weeks. The major efficacy outcome measures were progression-free survival (PFS) as assessed by a BICR RECIST v1.1, and overall survival (OS). Additional efficacy outcome measures included ORR and DoR assessed by BICR. A total of 713 patients were randomized: 476 patients to the IMFINZI arm and 237 to the placebo arm. The study population characteristics were: median age of 64 years (range: 23 to 90); 70% male; 69% White and 27% Asian; 16% current smokers, 75% former smokers, and 9% never smokers; 51% WHO performance status of 1; 53% with Stage IIIA and 45% were Stage IIIB; 46% with squamous and 54% with non-squamous histology. All patients received definitive radiotherapy as per protocol, of which 92% received a total radiation dose of 54 Gy to 66 Gy; 99% of patients received concomitant platinum-based chemotherapy (55% cisplatin-based, 42% carboplatin-based chemotherapy, and 2% switched between cisplatin and carboplatin). At a pre-specified interim analysis for OS based on 299 events (61% of total planned events), the study demonstrated a statistically significant improvement in OS in patients randomized to IMFINZI compared to placebo. The pre-specified interim analysis of PFS based on 371 events (81% of total planned events) demonstrated a statistically significant improvement in PFS in patients randomized to IMFINZI compared to placebo. Table 27 and Figure 2 summarizes the efficacy results for PACIFIC. Table 27. Efficacy Results for the PACIFIC Study Endpoint IMFINZI (N = 476) Among the ITT population, 7% in the IMFINZI arm and 10% in the placebo arm had non-measurable disease as assessed by BICR according to RECIST v1.1 Placebo (N = 237) Overall Survival (OS) OS results are based on the interim OS analysis conducted at 299 OS events which occurred 46 months after study initiation. Number of deaths 183 (38%) 116 (49%) Median in months (95% CI) NR (34.7, NR) 28.7 (22.9, NR) Hazard Ratio (95% CI) Two-sided p-value based on a log-rank test stratified by sex, age, and smoking history 0.68 (0.53, 0.87) p-value Compared with allocated α of 0.00274 (Lan‑DeMets spending function approximating O’Brien Fleming boundary) for interim analysis 0.0025 Progression-Free Survival (PFS) As assessed by BICR RECIST v1.1 PFS results are based on the interim PFS analysis conducted at 371 PFS events which occurred 33 months after study initiation. Number (%) of patients with event 214 (45%) 157 (66%) Median in months (95% CI) 16.8 (13.0, 18.1) 5.6 (4.6, 7.8) Hazard Ratio (95% CI) Pike estimator 0.52 (0.42, 0.65) p-value Compared with allocated α of 0.011035 (Lan‑DeMets spending function approximating O’Brien Fleming boundary) for interim analysis < 0.0001 Figure 2. Kaplan-Meier Curves of OS in the PACIFIC Study Metastatic NSCLC - POSEIDON The efficacy of IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy in previously untreated metastatic NSCLC patients with no sensitizing epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations was investigated in POSEIDON, a randomized, multicenter, active-controlled, open-label study (NCT03164616). Eligible patients had Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 and must have had no prior chemotherapy or any other systemic therapy for metastatic NSCLC. Choice of platinum-based chemotherapy was at the investigator’s discretion, taking into consideration the calculated creatinine clearance. Patients with active and/or untreated brain metastases; a history of active primary immunodeficiency; autoimmune disorders including active or prior documented autoimmune or inflammatory disorders; use of systemic immunosuppressants within 14 days before the first dose of the treatment except physiological dose of systemic corticosteroids were ineligible. Randomization was stratified by tumor cells (TC) PD-L1 expression (TC ≥ 50% vs. TC < 50%), disease stage (Stage IVA vs. Stage IVB), and histology (non-squamous vs. squamous). Patients were randomized 1:1:1 to receive IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy according to the regimens listed below, IMFINZI and platinum-based chemotherapy (an unapproved regimen for metastatic NSCLC), or platinum-based chemotherapy. The evaluation of efficacy for metastatic NSCLC relied on comparison between: • IMFINZI 1,500 mg with tremelimumab-actl 75 mg (or 1 mg/kg for patients < 30 kg) and platinum-based chemotherapy every 3 weeks for 4 cycles, followed by IMFINZI 1,500 mg every 4 weeks as a single agent. A fifth dose of tremelimumab-actl 75 mg (or 1 mg/kg for patients < 30 kg) was given at Week 16 in combination with IMFINZI dose 6. • Platinum-based chemotherapy every 3 weeks as monotherapy for 4 cycles. Patients could receive an additional 2 cycles (a total of 6 cycles post-randomization), as clinically indicated, at investigator’s discretion. Patients received IMFINZI in combination with tremelimumab-actl with one of the following platinum-based chemotherapy regimens: • Non-squamous NSCLC ∘ Pemetrexed 500 mg/m 2 with carboplatin AUC 5-6 or cisplatin 75 mg/m 2 every 3 weeks for 4 cycles. • Squamous NSCLC ∘ Gemcitabine 1,000 or 1,250 mg/m 2 on Days 1 and 8 with cisplatin 75 mg/m 2 or carboplatin AUC 5-6 on Day 1 every 3 weeks for 4 cycles. • Non-squamous and Squamous NSCLC ∘ Nab-paclitaxel 100 mg/m 2 on Days 1, 8, and 15 with carboplatin AUC 5-6 on Day 1 every 3 weeks for 4 cycles. Tremelimumab-actl was given up to a maximum of 5 doses. IMFINZI and histology-based pemetrexed continued every 4 weeks until disease progression or unacceptable toxicity. Administration of IMFINZI monotherapy was permitted beyond disease progression if the patient was clinically stable and deriving clinical benefit as determined by the investigator. Patients with disease progression during IMFINZI monotherapy were given the option to be retreated with 4 additional cycles of tremelimumab-actl in combination with IMFINZI. Tumor assessments were performed at Week 6, Week 12, and then every 8 weeks thereafter. The major efficacy outcome measures were progression free survival (PFS) and overall survival (OS) of IMFINZI and tremelimumab-actl in combination with platinum-based chemotherapy compared to platinum-based chemotherapy alone. Additional efficacy outcome measures were overall response rate (ORR) and duration of response (DoR). PFS, ORR, and DoR were assessed using Blinded Independent Central Review (BICR) according to RECIST v1.1. A total of 675 patients were randomized to receive either IMFINZI with tremelimumab-actl and platinum-based-chemotherapy (n = 338) or platinum-based chemotherapy (n = 337). The median age was 63 years (range: 27 to 87), 46% of patients age ≥ 65 years, 77% male, 57% White, 34% Asian, 0.3% Native Hawaiian or Other Pacific Islander, 3% American Indian or Alaska Native, 2% Black or African American, 4% Other Race, 79% former or current smoker, 34% ECOG PS 0, and 66% ECOG PS 1. Thirty-six percent had squamous histology, 63% non-squamous histology, 29% PD-L1 expression TC ≥ 50%, 71% PD-L1 expression TC < 50%. Efficacy results are summarized in Table 28 and Figure 3. Table 28. Efficacy Results for the POSEIDON Study IMFINZI with tremelimumab-actl and platinum-based chemotherapy (N = 338) Platinum-based chemotherapy (N = 337) OS PFS/OS results are based on planned analyses which occurred 25/45 months respectively after study initiation. Number of deaths (%) 251 (74) 285 (85) Median OS (months) (95% CI) 14.0 (11.7, 16.1) 11.7 (10.5, 13.1) HR (95% CI) 0.77 (0.65, 0.92) p-value 2-sided p-values based on log-rank tests stratified by PD-L1, histology and disease stage and compared to a boundary value of 0.00735 for PFS and 0.00797 for OS. 0.00304 PFS Number of events (%) 238 (70) 258 (77) Median PFS (months) (95% CI) 6.2 (5.0, 6.5) 4.8 (4.6, 5.8) HR (95% CI) 0.72 (0.60, 0.86) p-value 0.00031 ORR % (95% CI) Confirmed responses with 95% Clopper-Pearson confidence interval. 39 (34, 44) 24 (20, 29) Median DoR (months) (95% CI) 9.5 (7.2, NR) 5.1 (4.4, 6.0) NR=Not Reached, CI=Confidence Interval Figure 3. Kaplan-Meier Curves of OS in the POSEIDON Study figure1 figure2 figure3 14.2 Small Cell Lung Cancer (SCLC) Limited-stage SCLC - ADRIATIC The efficacy of IMFINZI was evaluated in the ADRIATIC Study (NCT03703297), a randomized, double-blind, placebo-controlled, multicenter study in 730 patients with histologically or cytologically confirmed LS-SCLC (Stage I to III according to AJCC, 8th edition) whose disease had not progressed following concurrent chemoradiation therapy (cCRT). Patients who had Stage I or II disease had to be medically inoperable as determined by the investigator. Eligible patients completed cCRT consisting of 4 cycles of platinum-based chemotherapy and either 60-66 Gy once daily over 6 weeks or 45 Gy twice daily over 3 weeks radiation therapy within 42 days prior to the first dose of IMFINZI or placebo. Prophylactic cranial irradiation (PCI) could be delivered at the discretion of the investigator after cCRT and had to be completed within 42 days prior to the first dose of IMFINZI or placebo. Patients with active or prior documented autoimmune disease within 5 years of initiation into the study; a history of active primary immunodeficiency; a history of Grade ≥ 2 pneumonitis or active tuberculosis or hepatitis B or C or HIV infection; active interstitial lung disease were ineligible. Patients with mixed SCLC and NSCLC histology were also ineligible. Randomization was stratified by stage (I/II versus III) and receipt of PCI (yes versus no). Patients were randomized 1:1:1 to receive IMFINZI as a single agent, IMFINZI in combination with another agent, or placebo. All study medications were administered intravenously. The evaluation of efficacy for LS-SCLC relied on comparison between: • Arm 1: IMFINZI 1,500 mg in combination with placebo every 4 weeks for 4 cycles, followed by IMFINZI 1,500 mg every 4 weeks. • Arm 2: Placebo in combination with a second placebo every 4 weeks for 4 cycles, followed by a single placebo every 4 weeks. A total of 530 patients were randomized between Arms 1 and 2, 264 patients to the IMFINZI arm and 266 patients to the placebo arm. Treatment continued until disease progression, until unacceptable toxicity, or for a maximum of 24 months. Tumor assessments were conducted every 8 weeks for the first 72 weeks, then every 12 weeks up to 96 weeks and then every 24 weeks thereafter. The major efficacy outcome measures were OS and PFS assessed by BICR according to RECIST v1.1. The baseline demographics and disease characteristics for patients in the IMFINZI and placebo arms were as follows: male (69%); age ≥ 65 years (39%); White (50%), Black or African-American (0.8%), Asian (48%), other race (1.3%); Hispanic or Latino (4.2%); current smoker (22%), past-smoker (68%), never smoker (9%); WHO/ECOG PS 0 (49%), WHO/ECOG PS 1 (51%); and Stage I (3.6%), Stage II (9%), Stage III (87%). Prior to randomization, all patients received platinum-based chemotherapy (66% cisplatin-etoposide, 34% carboplatin-etoposide) with 88% of patients receiving 4 cycles; 72% of patients received once daily radiation (of which 92% received ≥ 60 - ≤ 66 Gy QD); 28% received twice daily radiation (of which 97% received 45 Gy twice daily) and 54% of patients received PCI. Efficacy results are presented in Table 29 and Figure 4. Table 279. Efficacy Results for the ADRIATIC Study IMFINZI (N=264) Placebo (N=266) OS Number of deaths (%) 115 (44) 146 (55) Median OS (months) (95% CI) Calculated using the Kaplan Meier technique. CI for median derived based on Brookmeyer-Crowley method. 55.9 (37.3, NR) 33.4 (25.5, 39.9) HR (95% CI) Based on Cox proportional hazards model stratified by receipt of PCI. 0.73 (0.57, 0.93) p-value Compared with allocated alpha of 0.0168 for OS and 0.0280 for PFS (Lan‑DeMets spending function approximating O’Brien Fleming boundary) for interim analysis. 0.0104 PFS Assessed by BICR according to RECIST v1.1. Number of events (%) 139 (53) 169 (64) Median PFS (months) (95% CI) 16.6 (10.2, 28.2) 9.2 (7.4, 12.9) HR (95% CI) Based on Cox proportional hazards model stratified by TNM stage and receipt of PCI. 0.76 (0.61, 0.95) p-value 0.0161 Figure 4. Kaplan-Meier Curves of OS in the ADRIATIC Study Extensive-stage SCLC – CASPIAN The efficacy of IMFINZI in combination with etoposide and either carboplatin or cisplatin in previously untreated ES-SCLC was investigated in CASPIAN, a randomized, multicenter, active-controlled, open-label study (NCT03043872). Eligible patients had WHO Performance Status of 0 or 1 and were suitable to receive a platinum-based chemotherapy regimen as first-line treatment for SCLC. Patients with asymptomatic or treated brain metastases were eligible. Choice of platinum agent was at the investigator’s discretion, taking into consideration the calculated creatinine clearance. Patients with history of chest radiation therapy; a history of active primary immunodeficiency; autoimmune disorders including paraneoplastic syndrome; active or prior documented autoimmune or inflammatory disorders; use of systemic immunosuppressants within 14 days before the first dose of the treatment except physiological dose of systemic corticosteroids were ineligible. Randomization was stratified by the planned platinum-based therapy in cycle 1 (carboplatin or cisplatin). The evaluation of efficacy for ES-SCLC relied on comparison between: IMFINZI 1,500 mg, and investigator’s choice of carboplatin (AUC 5 or 6 mg/mL/min) or cisplatin (75-80 mg/m 2 ) on Day 1 and etoposide (80-100 mg/m 2 ) intravenously on Days 1, 2, and 3 of each 21-day cycle for 4 cycles, followed by IMFINZI 1,500 mg every 4 weeks until disease progression or unacceptable toxicity, or Investigator’s choice of carboplatin (AUC 5 or 6 mg/mL/min) or cisplatin (75-80 mg/m 2 ) on Day 1 and etoposide (80-100 mg/m 2 ) intravenously on Days 1, 2, and 3 of each 21-day cycle, up to 6 cycles. After completion of chemotherapy, PCI as administered per investigator discretion. Administration of IMFINZI as a single agent was permitted beyond disease progression if the patient was clinically stable and deriving clinical benefit as determined by the investigator. The major efficacy outcome measure was overall survival (OS) of IMFINZI plus chemotherapy vs. chemotherapy alone. Additional efficacy outcome measures were investigator-assessed progression-free survival (PFS) and objective response rate (ORR), per RECIST v1.1. The study population characteristics were: median age of 63 years (range: 28 to 82); 40% age 65 or older; 70% male; 84% White, 15% Asian, and 0.9% Black; 65% WHO/ECOG PS of 1; and 93% were former/current smokers. Ninety percent of patients had Stage IV disease and 10% had brain metastasis at baseline. A total of 25% of the patients received cisplatin and 74% of the patients received carboplatin. In the chemotherapy alone arm, 57% of the patients received 6 cycles of chemotherapy, and 8% of the patients received PCI. The OS results are summarized in Table 30 and Figure 5. Table 30. OS Results for the CASPIAN Study Endpoint IMFINZI with Etoposide and either Carboplatin or Cisplatin (N = 268) Etoposide and either Carboplatin or Cisplatin (N = 269) Overall Survival (OS) Number of deaths (%) At a pre-specified interim analysis, 336 OS events (79% of total planned events) were observed, and the boundary for declaring efficacy (0.0178) was determined by a Lan-Demets alpha spending function with O’Brien Fleming type boundary. 155 (58) 181 (67) Median OS (months) (95% CI) 13.0 (11.5, 14.8) 10.3 (9.3, 11.2) Hazard Ratio (95% CI) The analysis was performed using the stratified log-rank test, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin) and using the rank tests of association approach. 0.73 (0.59, 0.91) p-value 0.0047 Figure 5. Kaplan-Meier Curves of OS in the CASPIAN Study Investigator-assessed PFS (96% of total planned events) showed a HR of 0.78 (95% CI: 0.65, 0.94), with median PFS of 5.1 months (95% CI: 4.7, 6.2) in the IMFINZI plus chemotherapy arm and 5.4 months (95% CI: 4.8, 6.2) in the chemotherapy alone arm. The investigator-assessed confirmed ORR was 68% (95% CI: 62%, 73%) in the IMFINZI plus chemotherapy arm and 58% (95% CI: 52%, 63%) in the chemotherapy alone arm. In the exploratory subgroup analyses of OS based on the planned platinum chemotherapy received at cycle 1, the HR was 0.70 (95% CI 0.55, 0.89) in patients who received carboplatin, and the HR was 0.88 (95% CI 0.55, 1.41) in patients who received cisplatin. Figure_4 figure4 14.3 Biliary Tract Cancer (BTC) Locally Advanced or Metastatic BTC - TOPAZ-1 The efficacy of IMFINZI in combination with gemcitabine and cisplatin in patients with locally advanced or metastatic BTC was investigated in TOPAZ-1 (NCT03875235), a randomized, double-blind, placebo-controlled, multicenter study that enrolled 685 patients with histologically confirmed locally advanced unresectable or metastatic BTC who have not previously received systemic therapy. Patients with recurrent disease > 6 months after surgery and/or completion of adjuvant therapy were eligible. Patients had an ECOG Performance status of 0 and 1 and at least one target lesion by RECIST v1.1. Patients with ampullary carcinoma; active or prior documented autoimmune or inflammatory disorders; HIV infection or active infections, including tuberculosis or hepatitis C; current or prior use of immunosuppressive medication within 14 days before the first dose of IMFINZI were ineligible. Randomization was stratified by disease status (recurrent vs. initially unresectable) and primary tumor location (intrahepatic cholangiocarcinoma [ICCA] vs. extrahepatic cholangiocarcinoma [ECCA] vs. gallbladder cancer [GBC]). Patients were randomized 1:1 to receive: • IMFINZI 1,500 mg on Day 1+ gemcitabine 1,000 mg/m 2 and cisplatin 25 mg/m 2 on Days 1 and 8 of each 21-day cycle up to 8 cycles, followed by IMFINZI 1,500 mg every 4 weeks, or • Placebo on Day 1+ gemcitabine 1,000 mg/m 2 and cisplatin 25 mg/m 2 on Days 1 and 8 of each 21-day cycle up to 8 cycles, followed by placebo every 4 weeks. Treatment with IMFINZI or placebo continued until disease progression, or unacceptable toxicity. Treatment beyond disease progression was permitted if the patient was clinically stable and deriving clinical benefit as determined by the investigator. The major efficacy outcome measure was overall survival (OS). Additional efficacy outcome measures were investigator-assessed progression-free survival (PFS), objective response rate (ORR) and duration of response (DoR). Tumor assessments were conducted every 6 weeks for the first 24 weeks after the date of randomization, and then every 8 weeks until confirmed objective disease progression. The study population characteristics were: 50% male, median age of 64 years (range 20-85), 47% age 65 or older; 56% Asian, 37% White, 2% Black or African American, 0.1% American Indian or Alaskan Native, and 4% other; 51% had an ECOG PS of 1; primary tumor location was ICCA 56%, ECCA 18% and GBC 25%; 20% of patients had recurrent disease; 86% of patients had metastatic and 14% had locally advanced disease. At a pre-specified interim analysis, the study demonstrated a statistically significant improvement in OS and PFS in patients randomized to IMFINZI in combination with chemotherapy compared to placebo in combination with chemotherapy. Table 31 summarizes the efficacy results for TOPAZ-1. Table 31. Efficacy Results for the TOPAZ-1 Study Endpoint IMFINZI with Gemcitabine and Cisplatin (N = 341) Placebo with Gemcitabine and Cisplatin (N = 344) Overall Survival (OS) Number of deaths (%) 198 (58) 226 (66) Median OS (months) (95% CI) Kaplan-Meier estimated median with 95% CI derived using Brookmeyer-Crowley method 12.8 (11.1, 14) 11.5 (10.1, 12.5) Hazard Ratio (95% CI) Based on Cox proportional hazards model stratified by disease status and primary tumor location 0.80 (0.66, 0.97) p-value 2-sided p-value based on a stratified log-rank test compared with alpha boundary of 0.030 0.021 Progression-Free Survival (PFS) Number of patients with event (%) 276 (81) 297 (86) Median in months (95% CI) 7.2 (6.7, 7.4) 5.7 (5.6, 6.7) Hazard Ratio (95% CI) 0.75 (0.63, 0.89) p-value 2-sided p-value based on a stratified log-rank test compared with alpha boundary of 0.048 0.001 The investigator-assessed ORR was 27% (95% CI: 22% - 32%) in the IMFINZI plus chemotherapy arm and 19% (95% CI: 15%-23%) in the chemotherapy alone arm. Figure 6. Kaplan-Meier Curves of OS in the TOPAZ-1 Study figure5 14.4 Hepatocellular Carcinoma (HCC) Unresectable HCC - HIMALAYA The efficacy of IMFINZI in combination with tremelimumab-actl was evaluated in the HIMALAYA study (NCT03298451), a randomized (1:1:1), open-label, multicenter study in patients with confirmed uHCC who had not received prior systemic treatment for HCC. Patients were randomized to one of two investigational arms (IMFINZI plus tremelimumab-actl or IMFINZI) or sorafenib. Study treatment consisted of IMFINZI 1,500 mg in combination with tremelimumab-actl as a one-time single intravenous infusion of 300 mg on the same day, followed by IMFINZI every 4 weeks; IMFINZI 1,500 mg every 4 weeks; or sorafenib 400 mg given orally twice daily, until disease progression or unacceptable toxicity. The efficacy assessment of IMFINZI is based on patients randomized to the IMFINZI plus tremelimumab-actl arm versus the sorafenib arm. Randomization was stratified by macrovascular invasion (MVI) (yes or no), etiology of liver disease (hepatitis B virus vs. hepatitis C virus vs. others) and ECOG performance status (0 vs. 1). The study enrolled patients with BCLC Stage C or B (not eligible for locoregional therapy). The study excluded patients with co-infection of viral hepatitis B and hepatitis C; active or prior documented gastrointestinal (GI) bleeding within 12 months; ascites requiring non-pharmacologic intervention within 6 months; hepatic encephalopathy within 12 months before the start of treatment; active or prior documented autoimmune or inflammatory disorders. Esophagogastroduodenoscopy was not mandated prior to enrollment but adequate endoscopic therapy, according to institutional standards, was required for patients with history of esophageal variceal bleeding or those assessed as high risk for esophageal variceal bleeding by the treating physician. Study treatment was permitted beyond disease progression if the patient was clinically stable and deriving clinical benefit as determined by the investigator. The major efficacy outcome measure was overall survival (OS) between the IMFINZI plus tremelimumab-actl arm versus the sorafenib arm. Additional efficacy outcomes were investigator-assessed progression-free survival (PFS), objective response rate (ORR) and duration of response (DoR) according to RECIST v1.1. Tumor assessments were conducted every 8 weeks for the first 12 months and then every 12 weeks thereafter. The baseline demographics of the IMFINZI plus tremelimumab-actl and sorafenib arms were as follows: male (85%), age < 65 years (50%), median age of 65 years (range: 18 to 88 years), White (46%), Asian (49%), Black or African American (2%), Native Hawaiian or other Pacific Islander (0.1%), race Unknown (2%), Hispanic or Latino (5%), Not Hispanic or Latino (94%), ethnicity Unknown (1%), ECOG PS 0 (62%); Child-Pugh Class score A (99%), macrovascular invasion (26%), extrahepatic spread (53%), viral etiology; hepatitis B (31%), hepatitis C (27%), and uninfected (42%). Efficacy results are presented in Table 32 and Figure 7. Table 32. Efficacy Results for the HIMALAYA Study Endpoint IMFINZI and Tremelimumab-actl (N = 393) Sorafenib (N = 389) OS Number of deaths (%) 262 (66.7) 293 (75.3) Median OS (months) (95% CI) 16.4 (14.2, 19.6) 13.8 (12.3, 16.1) HR (95% CI) HR (IMFINZI and tremelimumab-actl vs. sorafenib) based on the stratified Cox proportional hazard model. 0.78 (0.66, 0.92) p-value Based on a stratified log-rank test. Based on a Lan-DeMets alpha spending function with O'Brien Fleming type boundary and the actual number of events observed, the boundary for declaring statistical significance for IMFINZI and tremelimumab-actl vs. sorafenib was 0.0398 (Lan and DeMets 1983). 0.0035 PFS Number of events (%) 335 (85.2) 327 (84.1) Median in (months) (95% CI) 3.8 (3.7, 5.3) 4.1 (3.7, 5.5) HR (95% CI) 0.90 (0.77, 1.05) ORR ORR % (95% CI) Confirmed complete response or partial response. Based on Clopper-Pearson method. 20.1 (16.3, 24.4) 5.1 (3.2, 7.8) Complete Response n (%) 12 (3.1) 0 Partial Response n (%) 67 (17.0) 20 (5.1) DoR Median DoR (months) (95% CI) 22.3 (13.7, NR) 18.4 (6.5, 26.0) % with duration ≥ 6 months 82.3 78.9 % with duration ≥ 12 months 65.8 63.2 CI=Confidence Interval, HR=Hazard Ratio, NR=Not Reached Figure 7. Kaplan-Meier Curves of OS in the Himalaya Study figure6 14.5 Endometrial cancer Advanced or Recurrent dMMR Endometrial Cancer - DUO-E IMFINZI was evaluated in combination with carboplatin and paclitaxel in DUO-E (NCT04269200), a randomized, multicenter, double-blind, placebo-controlled study in patients with advanced or recurrent endometrial cancer. The trial enrolled patients with newly diagnosed Stage III disease (with measurable disease per RECIST v1.1), or newly diagnosed Stage IV disease. The trial also enrolled patients with recurrent disease with a low potential for cure by radiation therapy or surgery. For patients with recurrent disease, prior chemotherapy was allowed only if it was administered in the adjuvant setting and at least 12 months had elapsed from the date of last dose of chemotherapy to the date of relapse. The trial included patients with epithelial endometrial carcinomas of all histologies, including carcinosarcomas. Patients with endometrial sarcoma were excluded, and patients who had active autoimmune disease or a medical condition that required immunosuppression were ineligible. Randomization was stratified by tumor mismatch repair (MMR) status (proficient or deficient), disease status (recurrent or newly diagnosed), and geographic region (Asia or rest of the world). MMR status was assessed using an FDA-approved test. Patients were randomized (1:1:1) to one of the following treatment arms: • IMFINZI 1,120 mg in combination with carboplatin and paclitaxel every 3 weeks for a maximum of 6 cycles. Following completion of chemotherapy treatment, patients received IMFINZI 1,500 mg every 4 weeks as maintenance treatment until disease progression. • Placebo in combination with carboplatin and paclitaxel every 3 weeks for a maximum of 6 cycles. Following completion of chemotherapy treatment, patients received placebo every 4 weeks as maintenance treatment until disease progression. • An additional investigational combination regimen. Treatment was continued until Response Evaluation Criteria in Solid Tumors (RECIST) v1.1-defined progression of disease or unacceptable toxicity. Assessment of tumor status was performed every 9 weeks for the first 18 weeks and every 12 weeks thereafter. The major efficacy outcome measure was progression-free survival (PFS), determined by investigator assessment using RECIST 1.1. Additional efficacy outcome measures included overall response rate (ORR), duration of response (DOR) and overall survival (OS). Among 95 patients with dMMR tumor, the baseline characteristics were median age of 63 years (range: 34 to 85); 47% age 65 or older; 62% White, 31% Asian, 2% Black or African American; 7% Hispanic or Latino, 1% American Indian or Alaska Native, and 4% other or not reported; ECOG PS of 0 (55%) or 1 (45%); 48% newly diagnosed (11% Stage III and 38% Stage IV) and 52% recurrent disease. The histologic subtypes were endometrioid (78%), mixed epithelial (6%), carcinosarcoma (5%), serous (4%), undifferentiated (1%), and other (5%). While a statistically significant improvement in PFS was observed in the overall population for IMFINZI with carboplatin and paclitaxel compared to carboplatin and paclitaxel alone, based on an exploratory analysis by MMR status, the PFS improvement in the overall population was primarily attributed to patients with dMMR tumors. Efficacy results for DUO-E are summarized in Table 33 and Figure 8 for patients with dMMR tumors. OS data in this subpopulation at the time of PFS analysis were immature with 26% of patients who died. Table 33. Efficacy Results for Patients with dMMR Tumors in the DUO-E Study Endpoint IMFINZI with Carboplatin and Paclitaxel N=46 Carboplatin and Paclitaxel N=49 PFS Investigator assessed. Number of events (%) 15 (32.6) 25 (51.0) Median in months (95% CI) Calculated using the Kaplan-Meier technique. NR (NR, NR) 7.0 (6.7, 14.8) HR (95% CI) 0.42 (0.22, 0.80) ORR N=42 N=42 ORR % (95% CI) 71.4 (55.4, 84.3) 40.5 (25.6, 56.7) Complete response % 12 (28.6) 4 (9.5) Partial response 18 (42.9) 13 (31.0) DOR Median in months (range) NR (2.4+, 26.9+) 10.5 (2.1+, 25.2+) CI=Confidence Interval, HR=Hazard Ratio, NR=Not Reached, + = response ongoing at last assessment. Figure 8. Kaplan-Meier curves of PFS for Patients with dMMR Tumors in the DUO-E Study figure7 14.6 Muscle invasive bladder cancer (MIBC) MIBC – NIAGARA Study The efficacy of neoadjuvant IMFINZI in combination with gemcitabine and cisplatin followed by adjuvant IMFINZI as a single agent in patients with MIBC was evaluated in NIAGARA (NCT03732677), a randomized, open-label, multicenter study. The study randomized (1:1) 1,063 patients who were candidates for radical cystectomy and who had not received prior systemic chemotherapy or immune-mediated therapy for the treatment of NMIBC or MIBC. The study excluded patients with pure non-urothelial histology, any small cell histology and primary non-bladder (i.e., ureter, urethral, or renal pelvis) cancer of the urothelium. Randomization was stratified by clinical tumor stage T2N0 vs. > T2N0 (including T2N1, T3, and T4a), renal function (creatinine clearance [CrCl] ≥ 60 mL/min vs. CrCl ≥ 40 mL/min to < 60 mL/min), and PD-L1 expression (high vs. low/negative). Patients received: • Neoadjuvant IMFINZI 1,500 mg plus gemcitabine 1,000 mg/m 2 and cisplatin 70 mg/m 2 every 3 weeks for 4 cycles prior to surgery, followed by IMFINZI 1,500 mg every 4 weeks as a single agent adjuvant treatment for up to 8 cycles after surgery, or • Neoadjuvant gemcitabine 1,000 mg/m 2 and cisplatin 70 mg/m 2 every 3 weeks for 4 cycles prior to surgery, without adjuvant treatment. Patients with CrCl ≥ 40 mL/min to < 60 mL/min in both arms received split-dose cisplatin of 35 mg/m 2 on days 1 and 8 of each cycle. A RECIST 1.1 tumor assessment was performed at baseline and upon completion of neoadjuvant therapy (prior to surgery). After surgery, tumor assessments were performed every 12 weeks for the first 24 months, then every 24 weeks for 36 months, and then every 52 weeks thereafter until progression, the end of study, or death. The major efficacy outcome measure was EFS by BICR assessment. OS was an additional efficacy outcome measure. Baseline demographics were: male (82%), median age 65 years (range: 32 to 84), age ≥65 years (53%), White (67%), Asian (28%), Black or African American (0.9%), other (0.8%), Hispanic or Latino (8%), and ECOG PS 0 (78%) vs. PS 1 (22%). Disease characteristics were: tumor stage T2N0 (40%) and >T2N0 (60%), regional lymph nodes N0 (95%) and N1 (5%), adequate renal function (81%) and borderline renal function (19%). The histologic subtypes included urothelial carcinoma (85%) and urothelial carcinoma with variant histology (15%). In the overall population, 469 (88%) patients in the IMFINZI plus gemcitabine and cisplatin arm and 441 (83%) patients in the gemcitabine and cisplatin arm underwent radical cystectomy. At a pre-specified interim analysis, the study demonstrated a statistically significant improvement in EFS and OS in the IMFINZI plus gemcitabine and cisplatin arm compared to the gemcitabine and cisplatin arm. The trial was not designed to isolate the effect of IMFINZI in each phase (neoadjuvant or adjuvant) of treatment. See Table 34 and Figures 9 and 10. Table 34. Efficacy Results for the NIAGARA Study IMFINZI plus gemcitabine and cisplatin (N=533) Gemcitabine and cisplatin (N = 530) EFS EFS is defined as the time from randomization to the first recurrence of disease after radical cystectomy, the time of first documented progression in patients who are medically precluded from a radical cystectomy, or time of expected surgery in patients who refuse to undergo a radical cystectomy or failure to undergo a radical cystectomy in participants with residual disease, or the time of death due to any cause, whichever occurs first. Number of events (%) 187. (35.1) 246 (46.4) Median EFS (months) (95% CI) NR (NR, NR) 46.1 (32.2, NR) HR (95% CI) Based on stratified Cox proportional hazard model. 0.68 (0.56, 0.82) 2-sided p-value Based on stratified log-rank test. , Alpha allocated at the interim analysis was 0.0412 for EFS and 0.0154 for OS. <0.0001 Overall Survival (OS) Number of events (%) 136.(25.5) 169 (31.9 Median OS (months) (95% CI) NR (NR, NR) NR (NR, NR) HR (95% CI) 0.75 (0.59, 0.93) 2-sided p-value , 0.0106 CI = Confidence Interval, HR = Hazard Ratio, NR = Not Reached Figure 9. Kaplan-Meier Curve of EFS Figure 10. Kaplan-Meier Curve of OS Figure_9 Figure_10 14.7 Gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) Neoadjuvant and Adjuvant Treatment of Resectable GC/GEJC – MATTERHORN Study The efficacy of IMFINZI with FLOT as neoadjuvant and adjuvant treatment, followed by IMFINZI as a single agent, was investigated in MATTERHORN (NCT04592913), a randomized, double-blind, placebo-controlled, multicenter study conducted in 948 patients with previously untreated and resectable GC/GEJC (Stage II to Stage IVA [AJCC, 8th edition]). Eligible patients had no prior exposure to immune-mediated therapy and a WHO/ECOG performance status of 0 or 1. Patients with active or prior documented autoimmune or inflammatory disorders, or use of immunosuppressive medication within 14 days of the first dose of durvalumab were ineligible. Randomization was stratified by geographic region (Asia vs. non-Asia), clinical lymph node status (positive vs. negative), and PD-L1 expression status (TAP < 1% vs. TAP ≥ 1%). Patients were randomized in a 1:1 ratio to one of the following treatment arms. Crossover between the study arms was not permitted. • IMFINZI 1,500 mg on Day 1 + FLOT on Days 1 and 15 of every 4-week cycle for 2 cycles in the neoadjuvant phase and 2 cycles in the adjuvant phase followed by IMFINZI 1,500 mg on Day 1 every 4 weeks for up to 10 additional cycles for a total of 12 cycles (1 dose per cycle) • Placebo on Day 1 + FLOT on Days 1 and 15 of every 4-week cycle for 2 cycles in the neoadjuvant phase and 2 cycles in the adjuvant phase followed by placebo on Day 1 every 4 weeks for up to 10 additional cycles for a total of 12 cycles (1 dose per cycle) Tumor assessment per RECIST was performed prior to the start of neoadjuvant therapy, prior to surgery, before starting adjuvant treatment and then every 12 weeks for 2 years and every 24 weeks until RECIST 1.1 defined radiological progression, consent withdrawal, or death. The major efficacy outcome measure of the study was EFS by BICR assessment. EFS was defined as the earliest of one of the following: disease progression according to RECIST 1.1 that precluded surgery or that required non-protocol therapy during the neoadjuvant treatment period; progression (after R1/R2 resection) or recurrence (after R0 resection), according to RECIST 1.1, during the adjuvant treatment period; non-RECIST progression (according to investigator assessment or confirmed by local pathology testing) that precluded surgery or that required non-protocol therapy during the neoadjuvant treatment period, or that was discovered during surgery; progression or recurrence confirmed by local pathology testing after surgery; or death. Additional efficacy outcome measures were OS and pCR rate by blinded central pathology review. The trial was not designed to isolate the effect of IMFINZI in each phase (neoadjuvant or adjuvant) of treatment. The demographics were as follows: median age 62 years (range: 26 to 84), age ≥65 years (41%), male (72%), White (68%), Asian (20%), American Indian or Alaska Native (4%), Black or African American (1.1%), other race (1.7%), Hispanic or Latino (20%), and WHO/ECOG PS 0 (74%). Disease characteristics were as follows: Stage II (29%), Stage III (62%), Stage IVA (9%), gastric (68%), gastroesophageal junction (32%), Siewert type 1 (10%), Siewert type 2 (15%), Siewert type 3 (7%), intestinal type (51%), diffuse type (26%), indeterminate type (23%), clinical lymph node status positive (70%), clinical lymph node status negative (29%), PD-L1 expression status TAP ≥1% (90%), and PD-L1 expression status TAP <1% (10%). There were 412 (87%) patients in the IMFINZI arm who completed curative intent surgery compared to 400 (84%) patients in the placebo arm. Surgery was delayed (defined as surgery attempt >8 weeks from last dose of neoadjuvant therapy) in 48 (10%) patients in the IMFINZI arm and 51 (11%) patients in the placebo arm. In the IMFINZI arm, 248 (52%) and 291 (61%) patients completed the two cycles of adjuvant IMFINZI and two cycles of adjuvant FLOT, respectively. In the placebo arm, 245 (52%) and 303 (64%) patients completed the two cycles of adjuvant placebo and two cycles of adjuvant FLOT, respectively. There were 344 (73%) patients in the IMFINZI arm who initiated adjuvant IMFINZI monotherapy compared to 332 (70%) patients in the placebo arm. The study demonstrated a statistically significant improvement in EFS in the IMFINZI arm compared to the placebo arm. See Table 35, Figure 11, and Figure 12. Table 35. Efficacy Results for the MATTERHORN Study IMFINZI + FLOT chemotherapy (N = 474) Placebo + FLOT chemotherapy (N = 474) Event Free Survival (EFS) Number of events, n (%) 167 (35) 218 (46) Median EFS (months) (95% CI) NR (40.7, NE) 32.8 (27.9, NE) HR (95% CI) 0.71 (0.58, 0.86) p-value <0.001 Overall Survival (OS) Number of events (%) 160 (33.8) 192 (40.5) Median OS (months) (95% CI) NR (NE, NE) NR (NE, NE) HR (95% CI) 0.78 (0.63, 0.96) p-value 0.021 pCR Results for EFS are based on a pre-specified interim analysis (DCO: 20 December 2024), results for OS are based on a pre-specified final analysis (DCO: 01 September 2025), and results for pCR are based on a pre-specified final analysis (DCO: 01 February 2023). Number of patients with response 91 34 Response rate, (%) (95% CI) 19.2 (15.7, 23.0) 7.2 (5.0, 9.9) p-value <0.001 CI=Confidence Interval, HR=Hazard Ratio, NE=Not estimable, NR=Not reached Figure 11. Kaplan-Meier Curve of EFS Figure 12. Kaplan-Meier Curve of OS Figure_11 Figure_12"],"pharmacodynamics":["12.2 Pharmacodynamics The steady state AUC, Ctrough, and C max in patients administered with 1,500 mg every 4 weeks are 6% higher, 19% lower, and 55% higher than those administered with 10 mg/kg every 2 weeks, respectively. Based on the modeling of pharmacokinetic data and exposure relationships for safety, there are no anticipated clinically meaningful differences in efficacy and safety for the doses of 1,500 mg every 4 weeks compared to 10 mg/kg every 2 weeks in patients weighing > 30 kg with NSCLC."],"pharmacokinetics":["12.3 Pharmacokinetics The pharmacokinetics of durvalumab as a single agent was studied in patients with doses ranging from 0.1 mg/kg (0.01 times the approved recommended dosage) to 20 mg/kg (2 times the approved recommended dosage) administered once every two, three, or four weeks. PK exposure increased more than dose-proportionally at doses < 3 mg/kg (0.3 times the approved recommended dosage) and dose proportionally at doses ≥ 3 mg/kg every 2 weeks. Steady state was achieved at approximately 16 weeks. The pharmacokinetics of durvalumab is similar when assessed as a single agent, when in combination with chemotherapy, when in combination with tremelimumab-actl and when in combination with tremelimumab-actl and platinum-based chemotherapy. Distribution The geometric mean (% coefficient of variation [CV%]) steady state volume of distribution (Vss) was 5.4 (13.1%) L. Elimination Durvalumab clearance decreases over time, with a mean maximal reduction (CV%) from baseline values of approximately 23% (57%) resulting in a geometric mean (CV%) steady state clearance (CLss) of 8 mL/h (39%) at day 365; the decrease in CLss is not considered clinically relevant. The geometric mean (CV%) terminal half-life, based on baseline CL was approximately 21 (26%) days. Specific Populations There were no clinically significant differences in the pharmacokinetics of durvalumab based on body weight (31 to 175 kg), age (18 to 96 years), sex, race (White, Black, Asian, Native Hawaiian, Pacific Islander, or Native American), albumin levels (4 to 57 g/L), lactate dehydrogenase levels (18 to 15,800 U/L), soluble PD-L1 (67 to 3,470 pg/mL), tumor type (NSCLC, SCLC, BTC and HCC), mild or moderate renal impairment (CLcr 30 to 89 mL/min), and mild or moderate hepatic impairment (bilirubin ≤ 3x ULN and any AST). The effect of severe renal impairment (CLcr 15 to 29 mL/min) or severe hepatic impairment (bilirubin > 3x ULN and any AST) on the pharmacokinetics of durvalumab is unknown."],"adverse_reactions":["6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling. • Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1) ]. • Infusion-Related Reactions [see Warnings and Precautions (5.2) ]. IMFINZI in Combination with Chemotherapy • Most common adverse reactions (≥ 20%) of patients with resectable, Stage II/III NSCLC [neoadjuvant /adjuvant]) are anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash. ( 6.1 ) IMFINZI as a Single Agent • Most common adverse reactions (≥ 20%) of patients with unresectable, Stage III NSCLC) are cough, fatigue, pneumonitis/radiation pneumonitis, upper respiratory tract infections, dyspnea, and rash. ( 6.1 ) IMFINZI in Combination with Tremelimumab-actl and Platinum-Based Chemothe rapy • Most common adverse reactions (≥ 20%) of patients with metastatic NSCLC) are nausea, fatigue, musculoskeletal pain, decreased appetite, rash, and diarrhea. ( 6.1 ) IMFINZI as a Single Agent • Most common adverse reactions (≥ 20%) of patients with limited-stage SCLC) are pneumonitis or radiation pneumonitis, and fatigue. ( 6.1 ) IMFINZI in Combination with Platinum-Based Chemotherapy • Most common adverse reactions (≥ 20%) of patients with extensive-stage SCLC) are nausea, fatigue/asthenia, and alopecia. ( 6.1 ) IMFINZI in Combination with Gemcitabine and Cisplatin • Most common adverse reactions (≥ 20%) of patients with BTC) are fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia. ( 6.1 ) IMFINZI in Combination with Tremelimumab-actl • Most common adverse reactions (≥ 20%) of patients with uHCC) are rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain. ( 6.1 ) IMFINZI in Combination with Carboplatin and Paclitaxel, followed by IMFINZI as a single agent • Most common adverse reactions (≥ 20%) of patients with endometrial cancer) were peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, decreased magnesium, increased ALT, increased AST, diarrhea, vomiting, cough, decreased potassium, dyspnea, headache, and increased alkaline phosphatase. ( 6.1 ) IMFINZI in Combination with Gemcitabine and Cisplatin, followed by IMFINZI as a single agent • Most common adverse reactions (≥ 20% of patients with MIBC) were decreased hemoglobin, decreased neutrophils, increased blood creatinine, decreased sodium, nausea, increased ALT, decreased calcium, decreased platelets, fatigue, increased potassium, decreased lymphocytes, increased AST, constipation, decreased magnesium, decreased appetite, increased alkaline phosphate, rash, pyrexia, diarrhea, vomiting and abdominal pain. ( 6.1 ) IMFINZI in Combination with FLOT Chemotherapy followed by IMFINZI as a single agent • Most common adverse reactions (≥ 20% of patients with resectable GC/GEJC) were diarrhea, nausea, peripheral neuropathy, fatigue, alopecia, decreased appetite, rash, abdominal pain, vomiting, musculoskeletal pain, pyrexia, and stomatitis ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described in the WARNINGS AND PRECAUTIONS section reflect exposure to IMFINZI as a single agent in a total of 1,889 patients enrolled in the PACIFIC study (a randomized, placebo-controlled study that enrolled 475 patients with unresectable Stage III NSCLC), Study 1108 (an open-label, single-arm, multicohort study that enrolled 970 patients with advanced solid tumors), and an additional open-label, single-arm study (ATLANTIC Study) that enrolled 444 patients with advanced solid tumors, including NSCLC. In these studies, IMFINZI was administered at a dose of 10 mg/kg every 2 weeks. Among the 1889 patients, 38% were exposed for 6 months or more and 18% were exposed for 12 months or more. The data also reflect exposure to IMFINZI 1,500 mg every 4 weeks as a single agent in 262 patients from the ADRIATIC study (a randomized, double-blind study in patients with LS-SCLC) and to IMFINZI in combination with chemotherapy in 265 patients from the CASPIAN study (a randomized, open-label study in patients with ES-SCLC) and in 338 patients from the TOPAZ-1 study (a randomized, double-blind study in patients with BTC). In the CASPIAN and TOPAZ-1 studies, IMFINZI was administered at a dose of 1,500 mg every 3 or 4 weeks. The data also reflect exposure to IMFINZI 1,120 mg in combination with carboplatin and paclitaxel (every 3 weeks for up to 6 cycles) followed by IMFINZI 1,500 mg (every 4 weeks) as a single agent in 235 patients in DUO-E (a randomized, placebo-controlled trial in endometrial cancer). Among the 235 patients, 77% (181 patients) were exposed to IMFINZI for 6 months or more and 41% (96 patients) for 12 months or more. The data also reflect exposure to IMFINZI 1,500 mg in combination with tremelimumab-actl 300 mg in 388 patients in HIMALAYA. In the HIMALAYA study patients received IMFINZI 1,500 mg in combination with tremelimumab-actl as a single intravenous infusion of 300 mg, followed by IMFINZI 1,500 mg every 4 weeks. The pooled safety population (N = 596) described in the WARNINGS AND PRECAUTIONS section reflect exposure to IMFINZI 1,500 mg in combination with tremelimumab-actl 75 mg and histology-based platinum chemotherapy regimens in 330 patients in POSEIDON [see Clinical Studies (14.1) ] , and 266 patients with ES-SCLC in CASPIAN who received up to four cycles of platinum-etoposide plus IMFINZI 1,500 mg with tremelimumab-actl 75 mg every 3 weeks, followed by IMFINZI 1,500 mg every 4 weeks (an unapproved regimen for extensive stage small cell lung cancer). Among the 596 patients, 55% were exposed to IMFINZI for 6 months or more and 24% were exposed for 12 months or more. The data described in this section reflect exposure to IMFINZI in patients with unresectable Stage III NSCLC enrolled in the PACIFIC study, in patients with metastatic NSCLC enrolled in the POSEIDON study, in patients with LS-SCLC enrolled in the ADRIATIC study, in patients with ES-SCLC enrolled in the CASPIAN study, in patients with BTC enrolled in the TOPAZ‑1 study, in patients with uHCC included in the HIMALAYA study, in patients with dMMR endometrial cancer enrolled in the DUO-E study, in patients with resectable NSCLC enrolled in the AEGEAN study, in patients with MIBC enrolled in the NIAGARA study and in patients with resectable GC/GEJC enrolled in the MATTERHORN study. Non-Small Cell Lung Cancer Neoadjuvant and Adjuvant Treatment of Resectable NSCLC – AEGEAN The safety of IMFINZI in combination with neoadjuvant platinum-containing chemotherapy followed by surgery, and continued adjuvant treatment with IMFINZI as a single agent after surgery, was investigated in AEGEAN, a randomized, double-blind, placebo-controlled, multicenter study for patients with resectable NSCLC (Stage IIA to select Stage IIIB [AJCC, 8 th edition]); squamous or non-squamous) [see Clinical Studies (14.1) ] . Safety data are available for the 799 patients who received IMFINZI in combination with chemotherapy (n=401) or placebo in combination with chemotherapy (n=398). The median duration of exposure to IMFINZI 1,500 mg every 3 weeks in the neoadjuvant phase was 12 weeks (range: 0 to 19 weeks). The median duration of exposure to IMFINZI 1,500 mg every 4 weeks in the adjuvant phase was 37 weeks (range: 4 to 67 weeks). The median age of patients who received IMFINZI was 65 years (range: 30 to 88), 52% age 65 or older, 12% age 75 or older; 65% male; 54% White, 41% Asian, 1% Black, 3% Other races; and 17% Hispanic or Latino. The most common adverse reactions (occurring in ≥ 20% of patients) were anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash. Table 5 summarizes the adverse reactions that occurred in (≥ 10%) patients treated with IMFINZI in combination with chemotherapy. Table 5. Adverse Reactions Occurring in ≥ 10% of Patients in the AEGEAN Study Adverse Reaction IMFINZI with Chemotherapy N=401 Placebo with Chemotherapy N=398 All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Gastrointestinal disorders Nausea 25 0.2 29 0.3 Constipation 25 0.2 21 0 Diarrhea includes colitis, diarrhea, enteritis, and proctitis. 14 1 13 1.3 Vomiting 11 0.7 11 1.0 General disorders and administration site conditions Fatigue includes fatigue and asthenia. 25 0 25 1.5 Skin and subcutaneous tissue disorders Rash includes dermatitis, dermatitis acneiform, drug eruption, eczema, eczema asteatotic, erythema, palmar‑erythrodysaesthesia syndrome, pemphigoid, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, and rash pustular, skin exfoliation, and urticarial dermatitis. 22 0.5 14 0.3 Pruritus 12 0.2 6 0 Musculoskeletal and connective tissue disorders Musculoskeletal pain includes arthralgia, arthritis, back pain, bone pain, chest pain, musculoskeletal chest pain, musculoskeletal pain, musculoskeletal discomfort, musculoskeletal stiffness,myalgia, neck pain, non-cardiac chest pain, pain in extremity, and spinal pain. 24 1 29 0.5 Metabolism and nutrition disorders Decreased appetite 18 0.2 18 0.3 Nervous system disorders Peripheral neuropathy includes dysaesthesia, hypoaesthesia, neuralgia, neuropathy peripheral, paraesthesia, peripheral sensory neuropathy, and polyneuropathy. 16 0.5 22 0.8 Endocrine disorders Hypothyroidism includes blood thyroid stimulating hormone increased and hypothyroidism. 11 0 3.8 0 Respiratory, thoracic and mediastinal disorders Cough / Productive cough 11 0 13 0 Pneumonia includes lower respiratory tract infection, lung abscess, paracancerous pneumonia, pneumonia, pneumonia aspiration, pneumonia bacterial, pneumonia chlamydial, pneumonia cryptococcal, pneumonia fungal, pneumonia pseudomonal, pneumonia streptococcal, pneumonia viral, and post-procedural pneumonia. , Five Grade 5 events in the IMFINZI arm and four Grade 5 events in the Placebo arm. 11 3.5 10 3 COVID-19 Includes COVID-19 and COVID-19 Pneumonia. Five Grade 5 events in the IMFINZI arm and One Grade 5 event in the placebo arm. 11 0.2 9 0.8 Psychiatric Disorders Insomnia 10 0 12 0 Table 6 summarizes the laboratory abnormalities in patients treated with IMFINZI in combination with chemotherapy. Table 6. Select Laboratory Abnormalities (≥20%) That Worsened from Baseline in Patients with Disease Who Received IMFINZI with Chemotherapy in AEGEAN Laboratory Abnormality Graded per NCI CTCAE V5. IMFINZI with Chemotherapy The denominator used to calculate the rate varied from 349 to 399 based on the number of patients with a baseline value and at least one post-treatment value. Placebo with Chemotherapy The denominator used to calculate the rate varied from 333 to 398 based on the number of patients with a baseline value and at least one post-treatment value. All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Hematology Hemoglobin decreased 78 10 75 9 Leukocytes decreased 63 12 64 11 Neutrophils decreased 52 24 56 27 Platelets decreased 46 7 44 8 Lymphocytes decreased 41 11 37 9 Chemistry Calcium corrected, decreased 51 3.3 52 4.5 Alanine aminotransferase increased 49 6 42 2 Aspartate aminotransferase increased 47 3.5 37 1.8 Potassium increased 33 1.5 29 2 Sodium decreased 35 5 33 6 Gamma glutamyl transferase increased 36 4.7 35 2.1 Creatinine increased 32 2.3 27 3.3 Amylase increased 25 4.7 24 3.6 Magnesium decreased 22 2.8 20 3.6 Lipase increased 23 4.9 24 7 Neoadjuvant Phase of AEGEAN A total of 401 patients received at least 1 dose of IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment and 398 patients received at least 1 dose of placebo in combination with platinum-containing chemotherapy as neoadjuvant treatment. Serious adverse reactions occurred in 21% of patients who received IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment; the most frequent (≥1%) serious adverse reactions were pneumonia (2.7%), anemia (1.5%), myelosuppression (1.5%), vomiting (1.2%), neutropenia (1%), and acute kidney injury (1%). Fatal adverse reactions occurred in 2% of patients, including death due to COVID-19 pneumonia (0.5%), sepsis (0.5%), myocarditis (0.2%), decreased appetite (0.2%), hemoptysis (0.2%), and death not otherwise specified (0.2%). Permanent discontinuation of any study drug due to an adverse reaction occurred in 14% of patients who received IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment; the most frequent (>0.5%) adverse reactions that led to permanent discontinuation of any study drug were anemia (1.5%), neutropenia (0.7%), myelosuppression (0.7%), and periphery sensory neuropathy (0.7%). Permanent discontinuation of IMFINZI due to an adverse reaction occurred in 6.7% of patients who received IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment; the most frequent (≥0.5%) adverse reactions that led to permanent discontinuation of IMFINZI were peripheral sensory neuropathy (0.7%) and pneumonitis (0.5%). Of the 401 IMFINZI-treated patients and 398 placebo-treated patients who received neoadjuvant treatment, 1.7% (n=7) and 1% (n=4), respectively, did not receive surgery due to adverse reactions. Adverse reactions that led to cancellation of surgery in the IMFINZI arm were COVID-19 pneumonia, HIV infection, pneumonitis, prostate cancer, colon cancer, pruritus, and colitis. Of the 325 IMFINZI-treated patients who received surgery, 4% (n=15) experienced delay of surgery (a surgical delay is defined as on-study surgery occurring more than 40 days after the last dose of study treatment in the neoadjuvant period) due to adverse reactions. Of the 326 placebo-treated patients who received surgery, 4% (n=16) experienced delay of surgery due to adverse reactions. Of the 325 IMFINZI-treated patients who received surgery, 6.5% (n=21) did not receive adjuvant treatment due to adverse reactions. Of the 326 placebo-treated patients who received surgery, 5.8% (n=19) did not receive adjuvant treatment due to adverse reactions. Adjuvant Phase of AEGEAN A total of 265 patients in the IMFINZI arm and 254 patients in the placebo arm received at least 1 dose of adjuvant treatment. Of the patients who received single agent IMFINZI as adjuvant treatment, 13% experienced serious adverse reactions. The most frequent serious adverse reactions reported in >1% of patients were pneumonia (1.9%), pneumonitis (1.1%), and COVID-19 (1.1%). Four fatal adverse reactions occurred during the adjuvant phase of the study, including COVID-19 pneumonia, pneumonia aspiration, interstitial lung disease and aortic aneurysm. Permanent discontinuation of adjuvant IMFINZI due to an adverse reaction occurred in 8% of patients. The most frequent (≥0.5%) adverse reaction that led to permanent discontinuation of adjuvant IMFINZI was pneumonitis (1.1%) and rash (0.8%). Unresectable Stage III NSCLC - PACIFIC The safety of IMFINZI in patients with Stage III NSCLC who completed concurrent platinum-based chemoradiotherapy within 42 days prior to initiation of study drug was evaluated in the PACIFIC study, a multicenter, randomized, double-blind, placebo-controlled study. A total of 475 patients received IMFINZI 10 mg/kg intravenously every 2 weeks. The study excluded patients who had disease progression following chemoradiation, with active or prior autoimmune disease within 2 years of initiation of the study or with medical conditions that required systemic immunosuppression [see Clinical Studies (14.1) ]. The study population characteristics were: median age of 64 years (range: 23 to 90), 45% age 65 years or older, 70% male, 69% White, 27% Asian, 75% former smoker, 16% current smoker, and 51% had WHO performance status (PS) of 1. All patients received definitive radiotherapy as per protocol, of which 92% received a total radiation dose of 54 Gy to 66 Gy. The median duration of exposure to IMFINZI was 10 months (range: 0.2 to 12.6). IMFINZI was discontinued due to adverse reactions in 15% of patients. The most common adverse reactions leading to IMFINZI discontinuation were pneumonitis or radiation pneumonitis in 6% of patients. Serious adverse reactions occurred in 29% of patients receiving IMFINZI. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation pneumonitis and fatal pneumonia occurred in < 2% of patients and were similar across arms. The most common adverse reactions (occurring in ≥ 20% of patients) were cough, fatigue, pneumonitis or radiation pneumonitis, upper respiratory tract infections, dyspnea, and rash. Table 7 summarizes the adverse reactions that occurred in at least 10% of patients treated with IMFINZI. Table 7. Adverse Reactions Occurring in ≥ 10% of Patients in the PACIFIC Study IMFINZI N = 475 Placebo N = 234 Adverse Reaction All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%) Respiratory, Thoracic, and Mediastinal Disorders Cough/Productive Cough 40 0.6 30 0.4 Pneumonitis Includes acute interstitial pneumonitis, interstitial lung disease, pneumonitis, pulmonary fibrosis. /Radiation Pneumonitis 34 3.4 25 3 Dyspnea Includes dyspnea, and exertional dyspnea. 25 1.5 25 2.6 General Disorders Fatigue Includes asthenia and fatigue. 34 0.8 32 1.3 Pyrexia 15 0.2 9 0 Infections Upper respiratory tract infections Includes laryngitis, nasopharyngitis, peritonsillar abscess, pharyngitis, rhinitis, sinusitis, tonsillitis, tracheobronchitis, and upper respiratory tract infection. 26 0.4 19 0 Pneumonia Includes lung infection, pneumocystis jirovecii pneumonia, pneumonia, pneumonia adenoviral, pneumonia bacterial, pneumonia cytomegaloviral, pneumonia haemophilus, pneumonia klebsiella, pneumonia necrotizing, pneumonia pneumococcal, and pneumonia streptococcal. 17 7 12 6 Skin and Subcutaneous Tissue Disorders Rash Includes rash erythematous, rash generalized, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, erythema, eczema, rash, and dermatitis. 23 0.6 12 0 Pruritus Includes pruritus generalized and pruritus. 12 0 6 0 Gastrointestinal Disorders Diarrhea 18 0.6 19 1.3 Abdominal pain Includes abdominal pain, abdominal pain lower, abdominal pain upper, and flank pain. 10 0.4 6 0.4 Endocrine Disorders Hypothyroidism Includes autoimmune hypothyroidism and hypothyroidism. 12 0.2 1.7 0 Other adverse reactions occurring in less than 10% of patients treated with IMFINZI were dysphonia, dysuria, night sweats, peripheral edema, and increased susceptibility to infections. Table 8 summarizes the laboratory abnormalities that occurred in at least 20% of patients treated with IMFINZI. Table 8. Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20% of Patients in the PACIFIC Study IMFINZI Placebo Laboratory Abnormality All Grades Graded according to NCI CTCAE version 4.0. (%) Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI (range: 464 to 470) and placebo (range: 224 to 228). Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Chemistry Hyperglycemia 52 8 51 8 Hypocalcemia 46 0.2 41 0 Increased ALT 39 2.3 22 0.4 Increased AST 36 2.8 21 0.4 Hyponatremia 33 3.6 30 3.1 Hyperkalemia 32 1.1 29 1.8 Increased GGT 24 3.4 22 1.7 Hematology Lymphopenia 43 17 39 18 Metastatic NSCLC - POSEIDON The safety of IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy in patients with metastatic NSCLC was evaluated in POSEIDON (NCT03164616), a randomized, open-label, multicenter, active-controlled study. A total of 330 patients received IMFINZI 1,500 mg in combination with tremelimumab-actl (≥ 30 kg body weight received 75 mg and < 30 kg body weight received 1 mg/kg) and histology-based platinum chemotherapy regimens [see Clinical Studies (14.1) ] . Of these patients, 66% received the maximum 5 doses of tremelimumab-actl and 79% received at least 4 doses. Treatment was continued with IMFINZI as a single agent (or with IMFINZI and histologically-based pemetrexed for non-squamous patients based on the investigator’s decision) until disease progression or unacceptable toxicity. The study excluded patients with active or prior autoimmune disease or with medical conditions that required systemic corticosteroids or immunosuppressants [see Clinical Studies (14.1) ]. The median age of patients who received IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy was 63 years (range: 27 to 87); 80% male; 61% White, 29% Asian, 58% former smoker, 25% current smoker, and 68% ECOG performance of 1. Serious adverse reactions occurred in 44% of patients receiving IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%), pyrexia (2.4%), and febrile neutropenia (2.1%). Fatal adverse reactions occurred in a total of 4.2% of patients receiving IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy. These include hepatitis, nephritis, myocarditis, pancreatitis (all in the same patient), death (2 patients), sepsis (2 patients), pneumonitis (2 patients), acute kidney injury (2 patients), febrile neutropenia (1 patient), chronic obstructive pulmonary disease (COPD) (1 patient), dyspnea (1 patient), sudden death (1 patient), and ischemic stroke (1 patient). Permanent discontinuation of IMFINZI or tremelimumab-actl due to an adverse reaction occurred in 17% of the patients. Adverse reactions which resulted in permanent discontinuation of IMFINZI or tremelimumab-actl in > 2% of patients included pneumonia. Dosage interruption or delay of IMFINZI and tremelimumab-actl due to an adverse reaction occurred in 41% of patients. Adverse reactions which required dosage interruption or delay of IMFINZI and tremelimumab-actl in > 1% of patients included anemia, leukopenia/white blood cell count decreased, pneumonia, pneumonitis, colitis, diarrhea, hepatitis, rash, asthenia, amylase increased, alanine aminotransferase increased, aspartate aminotransferase increased, lipase increased, neutropenia/ neutrophil count decreased, and thrombocytopenia/platelet count decreased. The most common adverse reactions (occurring in ≥ 20% of patients) were nausea, fatigue, musculoskeletal pain, decreased appetite, rash, and diarrhea. Grade 3 or 4 laboratory abnormalities (≥ 10%) were neutropenia, anemia, leukopenia, lymphocytopenia, lipase increased, hyponatremia and thrombocytopenia. Table 9 summarizes the adverse reactions in POSEIDON. Table 9. Adverse Reactions (≥ 10%) in Patients with NSCLC Who Received IMFINZI in the POSEIDON Study IMFINZI with tremelimumab-actl and platinum-based chemotherapy N = 330 Platinum-based chemotherapy N = 333 Adverse Reaction All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Gastrointestinal disorders Nausea 42 1.8 37 2.1 Diarrhea 22 1.5 15 1.5 Constipation 19 0 24 0.6 Vomiting 18 1.2 14 1.5 Stomatitis Includes mucosal inflammation and stomatitis. 10 0 6 0.3 General disorders and administration site conditions Fatigue/Asthenia Includes asthenia and fatigue. 36 5 32 4.5 Pyrexia Includes body temperature increased, hyperpyrexia, hyperthermia, and pyrexia. 19 0 8 0 Edema Includes face edema, localized edema, and edema peripheral. 10 0 10 0.6 Musculoskeletal and connective tissue disorders Musculoskeletal Pain Includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, and spinal pain. 29 0.6 22 1.5 Metabolism and nutrition disorders Decreased appetite 28 1.5 25 1.2 Skin and subcutaneous tissue disorders Rash Includes eczema, erythema, dermatitis, drug eruption, erythema multiforme, pemphigoid, rash, rash maculo-papular, rash papular, rash pruritic, and rash pustular. 27 2.4 10 0.6 Pruritus 11 0 4.5 0 Alopecia 10 0 6 0 Infections and Infestations Pneumonia Includes lower respiratory tract infection, pneumocystis jirovecii pneumonia, pneumonia, pneumonia aspiration, and pneumonia bacterial. 17 8 12 4.2 Upper respiratory tract infections Includes laryngitis, nasopharyngitis, pharyngitis, rhinitis, sinusitis, tonsillitis, tracheobronchitis and upper respiratory tract infection. 15 0.6 9 0.9 Endocrine disorders Hypothyroidism Includes blood thyroid stimulating hormone increased and hypothyroidism. 13 0 2.1 0 Respiratory, thoracic and mediastinal disorders Cough/Productive Cough Includes cough and productive cough. 12 0 8 0.3 Nervous system disorders Headache Includes headache and migraine. 11 0 8 0.6 Table 10 summarizes the laboratory abnormalities in POSEIDON. Table 10. Select Laboratory Abnormalities (≥ 10%) That Worsened from Baseline in Patients with NSCLC Who Received IMFINZI in the POSEIDON Study Laboratory Abnormality Graded according to NCI CTCAE version 4.03. IMFINZI with tremelimumab-actl and platinum-based chemotherapy The denominator used to calculate the rate varied from 45 to 326 based on the number of patients with a baseline value and at least one post-treatment value. Platinum-based chemotherapy The denominator used to calculate the rate varied from 43 to 323 based on the number of patients with a baseline value and at least one post-treatment value. All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Chemistry Blood creatinine increased 89 4 83 1.9 Increased ALT 64 6 56 4.7 Increased AST 63 5 55 2.2 Hypocalcemia 58 0.9 49 0.9 Hyponatremia 55 13 50 11 Hyperkalemia 49 2.2 35 2.8 Hyperglycemia 42 6 37 3.1 Amylase increased 41 9 25 6 Gamma Glutamyl Transferase increased 38 2.2 35 4.7 Lipase increased 35 14 25 5 Increased Alkaline Phosphatase 33 3.4 26 1.2 Albumin decreased 27 1.9 18 0.9 Hypokalemia 21 7 17 2.8 Bilirubinemia 16 0.9 8 0.3 Hypernatremia 15 0 14 0 Hypomagnesemia 12 4 23 0 Hematology Anemia 84 24 84 25 Leukopenia 77 21 81 18 Neutropenia 71 37 69 32 Lymphocytopenia 67 20 60 19 Thrombocytopenia 53 11 54 12 Small Cell Lung Cancer Limited Stage Small Cell Lung Cancer – ADRIATIC The safety of IMFINZI as a single agent in patients with LS-SCLC without disease progression following completion of concurrent platinum-based chemoradiotherapy (60-66 Gy once daily over 6 weeks or 45 Gy twice daily over 3 weeks) within 42 days prior to initiation of study drug, was evaluated in the ADRIATIC study, a multicenter, randomized, double-blind, placebo-controlled study [see Clinical Studies (14.2) ]. A total of 262 patients received IMFINZI 1,500 mg every 4 weeks until disease progression or unacceptable toxicity or a maximum of 24 months. The study excluded patients with Stage I or II LS-SCLC who were considered medically operable and patients with active or prior autoimmune disease or with medical conditions that required systemic corticosteroids or immunosuppressants. The study population characteristics were: median age of 62 years (range: 28 to 84); 39% age 65 years or older, 6% age 75 years or older; 69% male; 50% white, 48% Asian, 1.3% other races; 4.2% Hispanic or Latino; 68% former smoker, 22% current smoker; and 51% had WHO performance status of 1. Sixty-seven percent of patients received a total radiation dose of 60 Gy to 66 Gy once daily and 27% of patients received a total radiation dose of 45 Gy twice daily. The median duration of exposure to IMFINZI was 9.2 months (range: 0.92 to 25) in the IMFINZI arm. Serious adverse reactions occurred in 30% of patients receiving IMFINZI. The most frequent serious adverse reactions reported in ≥ 1% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (12%), and pneumonia (5%). Fatal adverse reactions occurred in 2.7% of patients who received IMFINZI including pneumonia (1.5%), cardiac failure, encephalopathy and pneumonitis (0.4% each). Permanent discontinuation of IMFINZI due to adverse reactions occurred in 16% of the patients. Adverse reactions which resulted in permanent discontinuation of IMFINZI in ≥ 1% of patients included pneumonitis or radiation pneumonitis (9%) and pneumonia (1.5%). Dosage interruptions of IMFINZI due to an adverse reaction occurred in 35% of patients. Adverse reactions which required dosage interruption in ≥ 5% of patients included pneumonitis or radiation pneumonitis (17%). The most common adverse reactions occurring in ≥ 20% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (38%), and fatigue (21%). Table 11 summarizes the adverse reactions that occurred in patients treated with IMFINZI in the ADRIATIC study. Table 11. Adverse Reactions (≥ 10%) in Patients with LS-SCLC Who Received IMFINZI in the ADRIATIC Study IMFINZI (N=262) Placebo (N=265) Adverse Reaction All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Respiratory, thoracic and mediastinal disorders Pneumonitis or Radiation pneumonitis Includes pneumonitis, immune-mediated lung disease, interstitial lung disease, radiation pneumonitis, and lung radiation fibrosis 38 3.1 30 2.6 Cough/Productive cough 17 0 14 0 Dyspnea Includes dyspnea and exertional dyspnea. 11 0.4 7 0 General disorders Fatigue Includes fatigue and asthenia. 21 0.4 20 2.3 Skin and subcutaneous tissue disorders Rash Includes dermatitis, acneiform dermatitis, eczema, rash, maculo-papular rash, papular rash, pruritic rash, and skin exfoliation. 18 0.4 11 0 Pruritus 13 0 7 0 Endocrine disorders Hypothyroidism Includes hypothyroidism, increased blood thyroid stimulating hormone, and decreased thyroxine free. 17 0 4.9 0 Hyperthyroidism Includes hyperthyroidism, decreased blood thyroid stimulating hormone, increased thyroxine free, increased thyroxine, increased tri-iodothyronine free, and increased tri-iodothyronine. 12 0 1.9 0 Metabolism and nutrition disorders Decreased appetite 17 0 13 0 Nervous system disorders Dizziness Includes dizziness, postural dizziness, vertigo, and positional vertigo. 14 0 9 0 Infections and infestations Pneumonia Includes pneumonia, atypical pneumonia, lower respiratory tract infection, bacterial pneumonia, pneumocystis jirovecii pneumonia, legionella pneumonia, and viral pneumonia. 13 3.1 9 4.2 Gastrointestinal disorders Nausea 13 0 11 0 Diarrhea 11 1.9 8 0 Constipation 10 0 10 0 Table 12 summarizes the laboratory abnormalities that occurred in at least 20% of patients treated with IMFINZI. Table 12. Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with LS-SCLC Who Received IMFINZI in the ADRIATIC Study Laboratory Abnormality Graded according to NCI CTCAE version 4.03, except creatinine increased which is graded according to NCI CTCAE version 5.0. IMFINZI The denominator used to calculate the rate varied from 63 to 259 based on the number of patients with a baseline value and at least one post-treatment value. Placebo The denominator used to calculate the rate varied from 65 to 262 based on the number of patients with a baseline value and at least one post-treatment value. All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Chemistry Hypocalcemia 43 0 43 0.8 Hyperglycemia 38 3.2 45 1.5 ALT increased 36 2.3 29 2.3 AST increased 33 2.3 28 1.5 Gamma Glutamyl Transferase increased 32 7 27 2.9 Hyponatremia 32 5 29 6.2 Hyperkalemia 23 1.2 17 0.8 Creatinine increased 21 0 17 0.8 Hematology Lymphocytes decreased 34 10 33 10 Leukocytes decreased 26 0.4 33 1.1 Extensive Stage Small Cell Lung Cancer – CASPIAN The safety of IMFINZI in combination with etoposide and either carboplatin or cisplatin in previously untreated ES-SCLC was evaluated in CASPIAN, a randomized, open-label, multicenter, active-controlled study. A total of 265 patients received IMFINZI 1,500 mg in combination with chemotherapy every 3 weeks for 4 cycles followed by IMFINZI 1,500 mg every 4 weeks until disease progression or unacceptable toxicity. The study excluded patients with active or prior autoimmune disease or with medical conditions that required systemic corticosteroids or immunosuppressants [see Clinical Studies (14.2) ] . Among 265 patients receiving IMFINZI, 49% were exposed for 6 months or longer and 19% were exposed for 12 months or longer. Among 266 patients receiving chemotherapy alone, 57% of the patients received 6 cycles of chemotherapy and 8% of the patients received prophylactic cranial irradiation (PCI) after chemotherapy. IMFINZI was discontinued due to adverse reactions in 7% of the patients receiving IMFINZI plus chemotherapy. These include pneumonitis, hepatotoxicity, neurotoxicity, sepsis, diabetic ketoacidosis and pancytopenia (1 patient each). Serious adverse reactions occurred in 31% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%) and COPD (1.1%). Fatal adverse reactions occurred in 4.9% of patients receiving IMFINZI plus chemotherapy. These include pancytopenia, sepsis, septic shock, pulmonary artery thrombosis, pulmonary embolism, and hepatitis (1 patient each) and sudden death (2 patients). The most common adverse reactions (occurring in ≥ 20% of patients) were nausea, fatigue/asthenia and alopecia. Table 13 summarizes the adverse reactions that occurred in patients treated with IMFINZI plus chemotherapy. Table 13. Adverse Reactions Occurring in ≥ 10% of Patients in the CASPIAN Study IMFINZI with etoposide and either carboplatin or cisplatin N = 265 Etoposide and either carboplatin or cisplatin N = 266 Adverse Reaction All Grades (%) Grade 3-4 (%) All Grades (%) Grade 3-4 (%) Gastrointestinal disorders Nausea 34 0.4 34 1.9 Constipation 17 0.8 19 0 Vomiting 15 0 17 1.1 Diarrhea 10 1.1 11 1.1 General disorders and administration site conditions Fatigue/Asthenia 32 3.4 32 2.3 Skin and subcutaneous tissue disorders Alopecia 31 1.1 34 0.8 Rash Includes rash erythematous, rash generalized, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, erythema, eczema, rash and dermatitis. 11 0 6 0 Metabolism and nutrition disorders Decreased appetite 18 0.8 17 0.8 Respiratory, thoracic and mediastinal disorders Cough/Productive Cough 15 0.8 9 0 Endocrine disorders Hyperthyroidism Includes hyperthyroidism and Basedow's disease. 10 0 0.4 0 Table 14 summarizes the laboratory abnormalities that occurred in at least 20% of patients treated with IMFINZI plus chemotherapy. Table 14. Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20% The frequency cut off is based on any grade change from baseline. of Patients in the CASPIAN Study IMFINZI with Etoposide and either Carboplatin or Cisplatin Etoposide and either Carboplatin or Cisplatin Laboratory Abnormality Grade Graded according to NCI CTCAE version 4.03. 3 or 4 (%) Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI (range: 258 to 263) and chemotherapy (range: 253 to 262) except magnesium IMFINZI with chemotherapy (18) and chemotherapy (16). Grade 3 or 4 (%) Chemistry Hyponatremia 11 13 Hypomagnesemia 11 6 Hyperglycemia 5 5 Increased Alkaline Phosphatase 4.9 3.5 Increased ALT 4.9 2.7 Increased AST 4.6 1.2 Hypocalcemia 3.5 2.4 Blood creatinine increased 3.4 1.1 Hyperkalemia 1.5 3.1 TSH decreased < LLN LLN = lower limit of normal. and ≥ LLN at baseline NA NA Hematology Neutropenia 41 48 Lymphopenia 14 13 Anemia 13 22 Thrombocytopenia 12 15 Biliary Tract Cancer Locally Advanced or Metastatic BTC - TOPAZ-1 The safety of IMFINZI in combination with gemcitabine and cisplatin in locally advanced or metastatic BTC was evaluated in TOPAZ-1, a randomized, double-blind, placebo-controlled, multicenter study. A total of 338 patients received IMFINZI 1,500 mg in combination with gemcitabine and cisplatin every 3 weeks up to 8 cycles followed by IMFINZI 1,500 mg every 4 weeks until disease progression or unacceptable toxicity. Patients with active or prior documented autoimmune or inflammatory disorders, HIV infection or other active infections, including tuberculosis or hepatitis C were ineligible [see Clinical Studies (14.3) ]. IMFINZI was discontinued due to adverse reactions in 6% of the patients receiving IMFINZI plus chemotherapy. The most frequently reported events resulting in discontinuation were sepsis (3 patients) and ischemic stroke (2 patients). The remaining events were dispersed across system organ classes and reported in 1 patient each. Serious adverse reactions occurred in 47% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 2% of patients were cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%) and acute kidney injury (2.4%). Fatal adverse reactions occurred in 3.6% of patients receiving IMFINZI plus chemotherapy. These include ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients) and upper gastrointestinal hemorrhage (2 patients). The most common adverse reactions (occurring in ≥ 20% of patients) were fatigue, nausea, constipation, decreased appetite, abdominal pain, rash and pyrexia. Table 15 summarizes the adverse reactions that occurred in patients treated with IMFINZI plus chemotherapy. Table 15. Adverse Reactions Occurring in ≥ 10% of Patients in the TOPAZ-1 Study IMFINZI with Gemcitabine and Cisplatin N = 338 Placebo with Gemcitabine and Cisplatin N = 342 Adverse Reaction All Grades Graded according to NCI CTCAE version 5.0. (%) Grade 3-4 (%) All Grades (%) Grade 3-4 (%) General disorders and administration site conditions Fatigue Includes fatigue, malaise, cancer fatigue and asthenia. 42 6 43 6 Pyrexia 20 1.5 16 0.6 Gastrointestinal disorders Nausea 40 1.5 34 1.8 Constipation 32 0.6 29 0.3 Abdominal pain Includes abdominal pain, abdominal pain lower, abdominal pain upper and flank pain. 24 0.6 23 2.9 Vomiting 18 1.5 18 2.0 Diarrhea 17 1.2 15 1.8 Metabolism and nutrition disorders Decreased appetite 26 2.1 23 0.9 Skin and subcutaneous tissue disorders Rash Includes rash macular, rash maculopapular, rash morbilliform, rash papular, rash pruritic, rash pustular, rash erythematous, dermatitis acneiform, dermatitis bullous, drug eruption, eczema, erythema, dermatitis and rash. 23 0.9 14 0 Pruritus 11 0 8 0 Psychiatric disorders Insomnia 10 0 11 0 Table 16 summarizes the laboratory abnormalities in patients treated with IMFINZI plus chemotherapy. Table 16. Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20% The frequency cut off is based on any grade change from baseline. of Patients in the TOPAZ-1 Study IMFINZI with Gemcitabine and Cisplatin Placebo with Gemcitabine and Cisplatin Laboratory Abnormality Grade Graded according to NCI CTCAE version 5.0. Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI with gemcitabine/cisplatin (range: 312 to 335) and Placebo with gemcitabine/cisplatin (range: 319 to 341). 3 or 4 (%) Grade 3 or 4 (%) Chemistry Hyponatremia 18 13 Gamma-glutamyltransferase increased 12 13 Increased bilirubin 10 14 Hypokalemia 8 4.4 Increased AST 8 8 Increased ALT 7 6 Blood creatinine increased 5 2.1 Hypomagnesemia 4.5 2.2 Hypoalbuminemia 3.6 2.9 Hyperkalemia 2.1 2.1 Increased Alkaline Phosphatase 1.8 3.8 Hypocalcemia 1.8 2.4 Hematology Neutropenia 48 49 Anemia 31 28 Leukopenia 28 28 Lymphopenia 23 15 Thrombocytopenia 18 18 Hepatocellular Carcinoma Unresectable HCC - HIMALAYA The safety of IMFINZI in combination with tremelimumab-actl was evaluated in a total of 388 patients with uHCC in HIMALAYA, a randomized, open-label, multicenter study [see Clinical Studies (14.1) ]. Patients received IMFINZI 1,500 mg administered as a single intravenous infusion in combination with tremelimumab-actl 300 mg on the same day, followed by IMFINZI every 4 weeks or sorafenib 400 mg given orally twice daily. Serious adverse reactions occurred in 41% of patients who received IMFINZI in combination with tremelimumab-actl. Serious adverse reactions in > 1% of patients included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%). Fatal adverse reactions occurred in 8% of patients who received IMFINZI in combination with tremelimumab-actl, including death (1%), hemorrhage intracranial (0.5%), cardiac arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and immune-mediated hepatitis (0.5%). The most common adverse reactions (occurring in ≥ 20% of patients) were rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain. Permanent discontinuation of treatment regimen due to an adverse reaction occurred in 14% of patients; the most common adverse reactions leading to treatment discontinuation (≥ 1%) were hemorrhage (1.8%), diarrhea (1.5%), AST increased (1%), and hepatitis (1%). Dosage interruptions or delay of the treatment regimen due to an adverse reaction occurred in 35% of patients. Adverse reactions which required dosage interruption or delay in ≥ 1% of patients included ALT increased (3.6%), diarrhea (3.6%), rash (3.6%), amylase increased (3.4%), AST increased (3.1%), lipase increased (2.8%), pneumonia (1.5%), hepatitis (1.5%), pyrexia (1.5%), anemia (1.3%), thrombocytopenia (1%), hyperthyroidism (1%), pneumonitis (1%), and blood creatinine increased (1%). Table 17 summarizes the adverse reactions that occurred in patients treated with IMFINZI in combination with tremelimumab-actl in the HIMALAYA study. Table 17. Adverse Reactions Occurring in ≥ 10% of Patients in the HIMALAYA Study IMFINZI and Tremelimumab-actl (N = 388) Sorafenib (N = 374) Adverse Reaction All Grades (%) Grade 3-4 (%) All Grades (%) Grade 3-4 (%) Skin and subcutaneous tissue disorders Rash Represents a composite of multiple related terms. 32 2.8 57 12 Pruritus 23 0 6 0.3 Gastrointestinal disorders Diarrhea 27 6 45 4.3 Abdominal pain 20 1.8 24 4 Nausea 12 0 14 0 General disorders and administration site conditions Fatigue 26 3.9 30 6 Pyrexia 13 0.3 9 0.3 Musculoskeletal and Connective Tissue Disorders Musculoskeletal pain 22 2.6 17 0.8 Metabolism and nutrition disorders Decreased appetite 17 1.3 18 0.8 Endocrine disorders Hypothyroidism 14 0 6 0 Psychiatric disorders Insomnia 10 0.3 4.3 0 Table 18 summarizes the laboratory abnormalities that occurred in patients treated with IMFINZI in combination with tremelimumab-actl in the HIMALAYA study. Table 18. Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20% of Patients in the HIMALAYA Study IMFINZI and Tremelimumab-actl Sorafenib Laboratory Abnormality Any grade Graded according to NCI CTCAE version 4.03. (%) Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI with tremelimumab-actl (range: 367-378) and sorafenib (range:344-352). Grade 3 or 4 (%) Any grade (%) Grade 3 or 4 (%) Chemistry Aspartate Aminotransferase increased 63 27 55 21 Alanine Aminotransferase increased 56 18 53 12 Sodium decreased 46 15 40 11 Bilirubin increased 41 8 47 11 Alkaline Phosphatase increased 41 8 44 5 Glucose increased 39 14 29 4 Calcium decreased 34 0 43 0.3 Albumin decreased 31 0.5 37 1.7 Potassium increased 28 3.8 21 2.6 Creatinine increased 21 1.3 15 0.9 Hematology Hemoglobin decreased 52 4.8 40 6 Lymphocytes decreased 41 11 39 10 Platelets decreased 29 1.6 35 3.1 Leukocytes decreased 20 0.8 30 1.1 Endometrial Cancer Advanced or Recurrent dMMR Endometrial Cancer – DUO-E The safety of IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent was evaluated in 44 patients with dMMR advanced or recurrent endometrial cancer in DUO-E, a randomized, double-blind, placebo-controlled trial [See Clinical Studies (14.5) ]. Patients received IMFINZI 1,120 mg with carboplatin and paclitaxel every 3 weeks for up to six 21-day cycles followed by IMFINZI 1,500 mg every 4 weeks or carboplatin and paclitaxel every 3 weeks for up to six 21-day cycles alone. Treatment was continued until disease progression or unacceptable toxicity. The median duration of exposure to IMFINZI with carboplatin and paclitaxel was 14.8 months (range: 0.7 to 31.7). Serious adverse reactions occurred in 30% of patients who received IMFINZI with carboplatin and paclitaxel. The most common serious adverse reactions (≥4%) were constipation (4.5%) and rash (4.5%). Permanent discontinuation of IMFINZI due to adverse reactions occurred in 11% of patients. The adverse reaction which resulted in permanent discontinuation of IMFINZI (≥4%) was rash (4.5%). Dosage interruptions of IMFINZI due to adverse reactions occurred in 52% of patients. Adverse reactions which required dosage interruptions of IMFINZI (≥ 4%) were anemia (11%), thrombocytopenia (9%), neutropenia (9%), COVID-19 (9%), increased ALT (4.5%), and pneumonitis (4.5%). The most common adverse reactions (> 20%), including laboratory abnormalities, were peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, decreased magnesium, increased ALT, increased AST, diarrhea, vomiting, cough, decreased potassium, dyspnea, headache, increased alkaline phosphatase, and decreased appetite. Tables 19 and 20 summarize adverse reactions and laboratory abnormalities in DUO-E, respectively. Table 19. Adverse Reactions Occurring in ≥ 10% of Patients with dMMR tumors in DUO-E Adverse Reactions IMFINZI with Carboplatin and Paclitaxel (N=44) Carboplatin and Paclitaxel (N=46) All Grades (%) Grade 3-4 (%) All Grades (%) Grade 3-4 (%) Nervous system disorders Peripheral neuropathy Includes neuropathy peripheral, peripheral sensory neuropathy, hypoasthesia, peripheral motor neuropathy, and parasthesia. 61 2.3 61 4.3 Headache 23 0 17 0 Musculoskeletal and connective tissue disorders Musculoskeletal pain Includes arthralgia, pain in extremity, back pain, non-cardiac chest pain, myalgia, musculoskeletal pain, musculoskeletal chest pain, arthritis, bone pain, musculoskeletal stiffness, neck pain, musculoskeletal discomfort, and spinal pain. 59 2.3 52 2.2 Gastrointestinal disorders Nausea 59 0 48 2.2 Abdominal pain Includes abdominal pain, abdominal pain lower, flank pain, abdominal discomfort, and abdominal pain upper. 39 0 24 2.2 Constipation Includes constipation and fecaloma. 39 4.5 35 2.2 Diarrhea 27 2.3 24 2.2 Vomiting 27 0 22 4.3 Skin and subcutaneous tissue disorders Alopecia 52 0 41 0 Rash Includes eczema, rash, rash erythematous, rash maculo-papular, dermatitis, rash pustular, skin exfoliation, and symmetrical drug-related intertriginous, and flexural exanthema. 39 2.3 17 2.2 Pruritus 16 0 11 0 General disorders and administration site conditions Fatigue Includes asthenia and fatigue. 41 4.5 57 11 Peripheral edema Includes peripheral edema, peripheral swelling, and edema. 16 0 13 2.2 Respiratory, thoracic and mediastinal disorders Cough / productive cough 27 0 20 0 Dyspnea Includes dyspnea and exertional dyspnea. 25 2.3 9 0 Metabolism and nutrition disorders Decreased appetite 18 0 18 0 Infections and infestations Upper respiratory tract infection Includes nasopharyngitis, pharyngitis, rhinitis, sinusitis, tracheobronchitis, and upper respiratory tract infection. 14 0 4.3 0 Endocrine disorders Hypothyroidism Includes blood thyroid stimulating hormone increased, and hypothyroidism. 11 0 4.3 0 Clinically relevant adverse reactions in < 10% of patients who received IMFINZI with carboplatin and paclitaxel included autoimmune hemolytic anemia, colitis, immune-mediated thyroiditis, infusion related reaction, interstitial lung disease, myositis, pneumonitis, pulmonary embolism, and sepsis. Table 20 summarizes the laboratory abnormalities that occurred in patients treated with IMFINZI with carboplatin and paclitaxel followed by IMFINZI as a single agent. Table 20. Select Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20% of Patients with dMMR tumors in DUO-E Laboratory Abnormality IMFINZI with Carboplatin and Paclitaxel Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI with carboplatin and paclitaxel (range: 40 to 44), and carboplatin and paclitaxel (range: 37 to 46) Carboplatin and Paclitaxel All Grades (%) Grade 3-4 (%) All Grades (%) Grade 3-4 (%) Chemistry Magnesium decreased 36 0 30 2.5 ALT increased 32 2.3 22 2.2 AST increased 30 2.3 22 0 Potassium decreased 25 0 24 2.2 Alkaline phosphatase increased 20 0 16 0 Muscle Invasive Bladder Cancer (MIBC) Neoadjuvant and adjuvant treatment of MIBC – NIAGARA The safety of IMFINZI in combination with neoadjuvant gemcitabine and cisplatin followed by surgery and continued IMFINZI treatment as adjuvant, single-agent therapy was evaluated in NIAGARA, a randomized, open-label, multicenter trial. Patients received IMFINZI in combination with chemotherapy (n=530) or received chemotherapy alone (n=526) [see Clinical Studies (14.6) ] . The median duration of exposure to IMFINZI 1,500 mg every 3 weeks in the neoadjuvant phase was 12 weeks (range: 1.1 to 84 weeks). The median duration of exposure to IMFINZI 1,500 mg every 4 weeks in the adjuvant phase was 32 weeks (range: 2.4 to 50 weeks). The most common adverse reactions, including laboratory abnormalities, in the overall study (occurring in ≥ 20% of patients) were decreased hemoglobin, decreased neutrophils, increased blood creatinine, decreased sodium, nausea, increased ALT, decreased calcium, decreased platelets, fatigue, increased potassium, decreased lymphocytes, increased AST, constipation, decreased magnesium, decreased appetite, increased alkaline phosphate, rash, pyrexia, diarrhea, vomiting, and abdominal pain. Table 21 summarizes the adverse reactions that occurred in patients treated with IMFINZI plus chemotherapy. Table 21. Adverse Reactions Occurring in ≥ 10% of Patients in the NIAGARA Study IMFINZI with gemcitabine and cisplatin N = 530 Gemcitabine and cisplatin N = 526 Adverse Reaction All Grades Graded according to NCI CTCAE version 5.0. (%) Grade 3-4 (%) All Grades (%) Grade 3-4 (%) Gastrointestinal disorders Nausea 54 1.5 48 1 Constipation 39 0.8 39 0.8 Diarrhea 21 1.5 14 0.4 Vomiting Includes multiple similar terms. 20 0.9 19 0.2 Abdominal pain 20 0.9 13 1 General disorders and administration site conditions Fatigue 52 2.3 49 3 Pyrexia 22 0.4 17 0 Edema 13 0.4 13 0 Metabolism and nutrition disorders Decreased appetite 27 0.6 25 0.6 Skin and subcutaneous tissue disorders Rash 23 1.3 12 0.6 Pruritus 15 0 7 0 Nervous system disorders Peripheral neuropathy 16 0.2 14 0 Headache 11 0 11 0 Dizziness 11 0 10 0.2 Endocrine disorders Hypothyroidism 13 0.4 2.3 0 Vascular disorders Hypertension 12 4.5 9 2.9 Hemorrhage 11 0.9 10 2.1 Table 22 summarizes the laboratory abnormalities in patients treated with IMFINZI plus chemotherapy. Table 22. Select Laboratory Abnormalities That Worsened from Baseline in ≥ 20% of Patients Who Received IMFINZI with Chemotherapy in the NIAGARA study Laboratory Abnormality IMFINZI with gemcitabine and cisplatin Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI plus chemotherapy (range: 482 to 528), and chemotherapy (range: 467 to 521). Gemcitabine and cisplatin All Grades Graded per NCI CTCAE V5. (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Chemistry Increased blood creatinine 63 9 58 7 Decreased sodium 54 9 55 10 Increased ALT 53 2.3 54 4.0 Decreased calcium 52 1.3 43 1.2 Increased potassium 51 4.2 49 4.4 Increased AST 42 1.5 39 2.1 Decreased magnesium 38 1.9 37 2.3 Increased alkaline phosphate 26 0.8 25 0.4 Hematology Decreased hemoglobin 88 13 87 13 Decreased neutrophils 76 31 74 34 Decreased platelets 52 6 50 7 Decreased lymphocytes 44 10 40 8 Neoadjuvant Phase of NIAGARA A total of 530 patients received at least 1 dose of IMFINZI in combination with chemotherapy as neoadjuvant treatment in the IMFINZI treatment arm, and 526 patients received at least 1 dose of chemotherapy as neoadjuvant treatment in the chemotherapy treatment arm. In the neoadjuvant phase, serious adverse reactions occurred in 24% of patients who received IMFINZI in combination with chemotherapy; the most frequent (≥1%) serious adverse reactions were pulmonary embolism (1.9%), febrile neutropenia (1.5%), acute kidney injury (1.3%), thrombocytopenia (1.3%), urinary tract infection (1.3%) and pneumonia (1.3%). Fatal adverse reactions occurred in 1.1% of patients including sepsis (0.2%), myocardial infarction (0.2%), and pulmonary embolism (0.2%). One fatal adverse reaction of pneumonia was reported in 1 (0.2%) patient in the post-surgery phase before adjuvant treatment started. Permanent discontinuation of IMFINZI due to an adverse reaction in the neoadjuvant phase occurred in 9% of patients while receiving IMFINZI in combination with chemotherapy. The most frequent (≥ 0.5%) adverse reactions that led to permanent discontinuation of IMFINZI were blood creatinine increased (0.9%), neutropenia (0.6%), acute kidney injury (0.6%), asthenia (0.6%) and fatigue (0.6%). Of the 530 patients in the IMFINZI treatment arm and 526 patients in the chemotherapy treatment arm who received neoadjuvant treatment, 1 (0.2%) patient in each treatment arm did not receive surgery due to adverse reactions. The adverse reaction that led to cancellation of surgery in the IMFINZI treatment arm was interstitial lung disease. Of the 469 patients in the IMFINZI treatment arm who underwent radical cystectomy, 4 (0.8%) patients experienced delay of surgery (defined as occurring more than 56 days after the last dose of neoadjuvant treatment) due to adverse reactions. Adjuvant Phase of NIAGARA A total of 383 patients (72%) in the IMFINZI treatment arm received at least 1 dose of adjuvant treatment. Serious adverse reactions occurred in 26% of patients receiving IMFINZI as adjuvant treatment. The most frequent serious adverse reactions (occurring in ≥1% of patients) were urinary tract infection (7%), acute kidney injury (3.7%), hydronephrosis (2.1%), pyelonephritis (2.1%), urosepsis (1.8%), and sepsis (1.6%). Fatal adverse reactions occurred in 1.8% of patients, including COVID-19 (0.3%), severe acute respiratory syndrome (0.3%), cardiopulmonary failure (0.3%), gastrointestinal haemorrhage (0.3%), and chronic hepatic failure (0.3%). Permanent discontinuation of adjuvant IMFINZI due to an adverse reaction occurred in 5% of patients. The most frequent (≥0.5%) adverse reactions that led to permanent discontinuation of adjuvant IMFINZI were nephritis (0.8%), fatigue (0.5%), diarrhea (0.5%), decreased appetite (0.5%) and pneumonitis (0.5%). Gastric or Gastroesophageal Junction Adenocarcinoma (GC/GEJC) Neoadjuvant and Adjuvant Treatment of Resectable GC/GEJC – MATTERHORN The safety of IMFINZI with FLOT as neoadjuvant and adjuvant treatment, followed by single-agent IMFINZI, was evaluated in MATTERHORN, a randomized, double-blind, placebo-controlled, multicenter study of patients with resectable GC/GEJC (Stage II to Stage IVA [AJCC, 8th edition]) [see Clinical Studies ( 14.7 )] . Safety data are available for the 944 patients who received IMFINZI with FLOT (n=475) or placebo with FLOT (n=469). The median duration of exposure to IMFINZI 1,500 mg every 4 weeks in the neoadjuvant phase was 8 weeks (range: 1.4 to 8.7 weeks). The median duration of exposure to IMFINZI 1,500 mg every 4 weeks in the adjuvant phase was 48 weeks (range: 1.9 to 50.1 weeks). The most common adverse reactions (occurring in ≥ 20% of patients) were diarrhea, nausea, peripheral neuropathy, fatigue, alopecia, decreased appetite, rash, abdominal pain, vomiting, musculoskeletal pain, pyrexia, and stomatitis. Table 23 summarizes the adverse reactions that occurred in ≥ 10% of patients treated with IMFINZI in combination with FLOT chemotherapy. Table 23: Adverse Reactions Occurring in ≥ 10% of Patients in the MATTERHORN study Adverse Reaction IMFINZI with FLOT Chemotherapy N=475 Placebo with FLOT Chemotherapy N=469 All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Gastrointestinal disorders Diarrhea Includes multiple similar terms. 64 8 59 7 Nausea 51 2.5 51 1.5 Vomiting 26 2.1 26 3 Abdominal pain 27 2.3 29 1.3 Stomatitis 20 1.1 15 0.6 Constipation 16 0 17 0.9 Dysphagia 10 1.5 8 1.5 Nervous system disorders Peripheral neuropathy 51 3.6 47 2.3 Dysgeusia 19 0 15 0 General disorders and administration site conditions Fatigue 47 5 45 5 Pyrexia 20 0.8 16 1.3 Skin and subcutaneous tissue disorders Alopecia 31 0 32 0 Rash 30 1.5 20 0.4 Pruritus 11 0 5 0 Metabolism and nutrition disorders Decreased appetite 31 3.2 30 2.1 Musculoskeletal and connective tissue disorders Musculoskeletal pain 21 1.5 19 0.6 Infections and infestations COVID-19 19 1.7 16 0.6 Pneumonia 11 3.8 10 4.3 Investigations Weight decreased 15 2.1 19 3.4 Vascular disorders Hemorrhage 14 2.5 15 2.8 Respiratory, thoracic and mediastinal disorders Cough 10 0 10 0 Table 24 summarizes the laboratory abnormalities in patients treated with IMFINZI in combination with FLOT chemotherapy. Table 24: Laboratory Abnormalities (> 20%) That Worsened from Baseline in Patients with Disease Who Received IMFINZI with FLOT Chemotherapy in MATTERHORN Laboratory Abnormality Graded per NCI CTCAE v5.0 IMFINZI with FLOT Chemotherapy The denominator used to calculate the rate varied from 444 to 472 based on the number of patients with a baseline value and at least one post-treatment value. Placebo with FLOT Chemotherapy The denominator used to calculate the rate varied from 443 to 468 based on the number of patients with a baseline value and at least one post-treatment value. All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Hematology Decreased leukocytes 75 14 79 17 Decreased neutrophils 70 41 74 44 Decreased hemoglobin 68 7 73 8 Decreased lymphocytes 49 13 45 13 Decreased platelets 47 1.1 46 1.9 Chemistry Increased AST 72 6 69 6 Increased ALT 70 7 65 6 Increased GGT 57 10 51 6 Increased lipase 55 16 55 15 Increased alkaline phosphatase 53 3.2 51 1.5 Decreased calcium 45 0.8 47 2.6 Increased amylase 42 6 39 4.5 Decreased potassium 39 8 40 8 Decreased sodium 33 4.4 32 4.7 Decreased albumin 31 1.5 31 0.2 Increased potassium 22 0.6 26 1.3 Adverse Reactions by Phase of Treatment Table 25 summarizes safety profile by Phase of treatment. Table 25: Safety Profile by Phase of Treatment IMFINZI with FLOT Chemotherapy Placebo with FLOT Chemotherapy Neoadjuvant Phase Number of Patients 475 469 Serious Adverse Reactions 21% 18% Deaths during Treatment-emergent period 1.9% 1.7% Permanent discontinuation of IMFINZI or Placebo 2.5% 2.1% No surgery due to Adverse Reaction 0.6% 0.4% Delay in surgery due to Adverse Reaction 2.3% 2.6% Adjuvant Phase Number of Patients 365 351 Serious Adverse Reactions 29% 26% Deaths during Treatment-emergent period 2.2% 2.6% Permanent discontinuation of IMFINZI or Placebo 7% 4.6% Adjuvant Phase (IMFINZI as a single-agent) Number of Patients 345 331 Serious Adverse Reactions 14% 15% Deaths during Treatment-emergent period 1.7% 2.4% Permanent discontinuation of IMFINZI or Placebo 6% 2.7% Serious adverse reactions (≥2%) in the IMFINZI arm were diarrhea (2.5%) during the neoadjuvant phase, and pneumonia (2.5%) in the adjuvant phase. Deaths (≥2 patients) in the IMFINZI arm were septic shock (0.6%) and acute coronary syndrome (0.4%) during the neoadjuvant phase; gastrointestinal perforation (0.5%) and COVID-19 (0.5%) during adjuvant phase; and gastrointestinal perforation (0.6%) and COVID-19 (0.6%) in the single-agent adjuvant phase. Permanent discontinuation of IMFINZI (≥2 patients) due an adverse reaction in the IMFINZI arm were nephritis (0.4%) during the neoadjuvant phase; hepatitis (1.1%), pneumonitis (1.1%), rash (0.8%), musculoskeletal pain (0.5%), and renal failure (0.5%) during adjuvant phase; and hepatitis (0.9%), pneumonitis (0.9%), musculoskeletal pain (0.6%), and renal failure (0.6%) during the single-agent adjuvant phase."],"contraindications":["4 CONTRAINDICATIONS None. None. ( 4 )"],"mechanism_of_action":["12.1 Mechanism of Action Expression of programmed cell death ligand-1 (PD-L1) can be induced by inflammatory signals (e.g., IFN-gamma) and can be expressed on both tumor cells and tumor-associated immune cells in the tumor microenvironment. PD-L1 blocks T-cell function and activation through interaction with PD-1 and CD80 (B7.1). By binding to its receptors, PD-L1 reduces cytotoxic T-cell activity, proliferation, and cytokine production. Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80 (B7.1). Blockade of PD-L1/PD-1 and PD-L1/CD80 interactions releases the inhibition of immune responses, without inducing antibody dependent cell-mediated cytotoxicity (ADCC). PD-L1 blockade with durvalumab led to increased T-cell activation in vitro and decreased tumor size in co-engrafted human tumor and immune cell xenograft mouse models."],"recent_major_changes":["Indications and Usage ( 1.1 , 1.2 ) 12/2024 Indications and Usage ( 1.5 ) 02/2025 Indications and Usage ( 1.6 ) 03/2025 Indications and Usage ( 1.7 ) 11/2025 Dosage and Administration ( 2.1 ) 02/2025 Dosage and Administration ( 2.1 , 2.2 , 2.3 , 2.4 ) 12/2024 Dosage and Administration ( 2.2 , 2.4 ) 03/2025 Dosage and Administration ( 2.2 ) 11/2025 Warnings and Precautions ( 5.1 ) 12/2024"],"clinical_pharmacology":["12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Expression of programmed cell death ligand-1 (PD-L1) can be induced by inflammatory signals (e.g., IFN-gamma) and can be expressed on both tumor cells and tumor-associated immune cells in the tumor microenvironment. PD-L1 blocks T-cell function and activation through interaction with PD-1 and CD80 (B7.1). By binding to its receptors, PD-L1 reduces cytotoxic T-cell activity, proliferation, and cytokine production. Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80 (B7.1). Blockade of PD-L1/PD-1 and PD-L1/CD80 interactions releases the inhibition of immune responses, without inducing antibody dependent cell-mediated cytotoxicity (ADCC). PD-L1 blockade with durvalumab led to increased T-cell activation in vitro and decreased tumor size in co-engrafted human tumor and immune cell xenograft mouse models. 12.2 Pharmacodynamics The steady state AUC, Ctrough, and C max in patients administered with 1,500 mg every 4 weeks are 6% higher, 19% lower, and 55% higher than those administered with 10 mg/kg every 2 weeks, respectively. Based on the modeling of pharmacokinetic data and exposure relationships for safety, there are no anticipated clinically meaningful differences in efficacy and safety for the doses of 1,500 mg every 4 weeks compared to 10 mg/kg every 2 weeks in patients weighing > 30 kg with NSCLC. 12.3 Pharmacokinetics The pharmacokinetics of durvalumab as a single agent was studied in patients with doses ranging from 0.1 mg/kg (0.01 times the approved recommended dosage) to 20 mg/kg (2 times the approved recommended dosage) administered once every two, three, or four weeks. PK exposure increased more than dose-proportionally at doses < 3 mg/kg (0.3 times the approved recommended dosage) and dose proportionally at doses ≥ 3 mg/kg every 2 weeks. Steady state was achieved at approximately 16 weeks. The pharmacokinetics of durvalumab is similar when assessed as a single agent, when in combination with chemotherapy, when in combination with tremelimumab-actl and when in combination with tremelimumab-actl and platinum-based chemotherapy. Distribution The geometric mean (% coefficient of variation [CV%]) steady state volume of distribution (Vss) was 5.4 (13.1%) L. Elimination Durvalumab clearance decreases over time, with a mean maximal reduction (CV%) from baseline values of approximately 23% (57%) resulting in a geometric mean (CV%) steady state clearance (CLss) of 8 mL/h (39%) at day 365; the decrease in CLss is not considered clinically relevant. The geometric mean (CV%) terminal half-life, based on baseline CL was approximately 21 (26%) days. Specific Populations There were no clinically significant differences in the pharmacokinetics of durvalumab based on body weight (31 to 175 kg), age (18 to 96 years), sex, race (White, Black, Asian, Native Hawaiian, Pacific Islander, or Native American), albumin levels (4 to 57 g/L), lactate dehydrogenase levels (18 to 15,800 U/L), soluble PD-L1 (67 to 3,470 pg/mL), tumor type (NSCLC, SCLC, BTC and HCC), mild or moderate renal impairment (CLcr 30 to 89 mL/min), and mild or moderate hepatic impairment (bilirubin ≤ 3x ULN and any AST). The effect of severe renal impairment (CLcr 15 to 29 mL/min) or severe hepatic impairment (bilirubin > 3x ULN and any AST) on the pharmacokinetics of durvalumab is unknown. 12.6 Immunogenicity The observed incidence of anti-drug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparison of the incidence of ADAs in the studies described below with the incidence of ADAs in other studies including those of IMFINZI or of other durvalumab products. In clinical trials of patients who received IMFINZI for 10 to 48 weeks at dosages of 1,500 mg every 4 weeks, 10 mg/kg every 2 weeks, 20 mg/kg every 4 weeks as a single agent or 1,120 mg every 3 weeks, or 1,500 mg every 3 weeks in the combination therapies, 3.6% (199/5562) of evaluable patients tested positive for treatment-emergent anti-durvalumab antibodies, and 8.5% (17/199) of treatment-emergent ADA positive patients had neutralizing antibodies against durvalumab. There were no identified clinically significant effects of ADAs on durvalumab pharmacokinetics or safety; however, the effect of these ADAs on the effectiveness of IMFINZI is unknown."],"indications_and_usage":["1 INDICATIONS AND USAGE IMFINZI is a programmed death-ligand 1 (PD-L1) blocking antibody indicated: • in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, for the treatment of adult patients with resectable (tumors ≥ 4 cm and/or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. ( 1.1 ) • as a single agent, for the treatment of adult patients with unresectable, Stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. ( 1.1 ) • in combination with tremelimumab-actl and platinum-based chemotherapy, for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations. ( 1.1 ) • as a single agent, for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. ( 1.2 ) • in combination with etoposide and either carboplatin or cisplatin, as first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). ( 1.2 ) • in combination with gemcitabine and cisplatin, as treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC). ( 1.3 ) • in combination with tremelimumab-actl, for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). ( 1.4 ) • in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent, for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-approved test. ( 1.5 , 2.1 ) • in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single agent IMFINZI as adjuvant treatment following radical cystectomy, for the treatment of adult patients with muscle invasive bladder cancer (MIBC). ( 1.6 ) • in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy as neoadjuvant and adjuvant treatment, followed by single agent IMFINZI, for the treatment of adult patients with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC). ( 1.7 ) 1.1 Non-Small Cell Lung Cancer • IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, is indicated for the treatment of adult patients with resectable (tumors ≥ 4 cm and/or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. • IMFINZI, as a single agent, is indicated for the treatment of adult patients with unresectable Stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT). • IMFINZI, in combination with tremelimumab-actl and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations. 1.2 Small Cell Lung Cancer • IMFINZI, as a single agent, is indicated for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT). • IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). 1.3 Biliary Tract Cancers IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC). 1.4 Hepatocellular Carcinoma IMFINZI, in combination with tremelimumab-actl, is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). 1.5 Endometrial Cancer IMFINZI, in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-approved test [see Dosage and Administration (2.1)]. 1.6 Bladder Cancer IMFINZI in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single agent IMFINZI as adjuvant treatment following radical cystectomy, is indicated for the treatment of adult patients with muscle invasive bladder cancer (MIBC). 1.7 Gastric or gastroesophageal junction adenocarcinoma IMFINZI in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) as neoadjuvant and adjuvant treatment, followed by single-agent IMFINZI, is indicated for the treatment of adult patients with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC)."],"warnings_and_cautions":["5 WARNINGS AND PRECAUTIONS • Immune-Mediated Adverse Reactions ( 5.1 ) ∘ Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis and renal dysfunction, solid organ transplant rejection, and immune-mediated pancreatitis. o Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. o Withhold or permanently discontinue based on severity and type of reaction. • Infusion-Related Reactions: Interrupt, slow the rate of infusion, or permanently discontinue IMFINZI based on the severity of the reaction. ( 5.2 ) • Complications of Allogeneic HSCT: Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD-1/PD-L1 blocking antibody. (5.3) • Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception. ( 5.4 , 8.1 , 8.3 ) 5.1 Immune-Mediated Adverse Reactions IMFINZI is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. The incidence and severity of immune-mediated adverse reactions were similar when IMFINZI was administered as a single agent or in combination with chemotherapy or in combination with tremelimumab-actl and platinum-based chemotherapy, unless otherwise noted. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD 1/PD L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI depending on severity [see Dosage and Administration (2.3) ] . In general, if IMFINZI requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below. Immune-Mediated Pneumonitis IMFINZI can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. IMFINZI as a Single Agent In Patients Who Did Not Receive Recent Prior Radiation In patients who received IMFINZI on clinical studies in which radiation therapy was generally not administered immediately prior to initiation of IMFINZI, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (< 0.1%), and Grade 3-4 (0.4%) adverse reactions. Events resolved in 19 of the 34 patients and resulted in permanent discontinuation in 5 patients. Systemic corticosteroids were required in 19 patients (19/34) with pneumonitis who did not receive chemoradiation prior to initiation of IMFINZI. The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar whether IMFINZI was given as a single agent in patients with various cancers in a pooled data set or in patients with ES-SCLC or BTC when given in combination with chemotherapy. In Patients Who Received Recent Prior Radiation The incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3% (87/475) in patients receiving IMFINZI and 12.8% (30/234) in patients receiving placebo. Of the patients who received IMFINZI (475), 1.1% had a fatal adverse reaction and 2.7% had Grade 3 adverse reactions. Events resolved in 50 of the 87 (57%) patients and resulted in permanent discontinuation in 27 of the 87 (31%) patients. Systemic corticosteroids were required in 64 patients (64/87) with pneumonitis who had received chemoradiation prior to initiation of IMFINZI, while 2 patients required use of infliximab with high-dose steroids. The incidence of pneumonitis (including radiation pneumonitis) in patients with LS-SCLC following chemoradiation within 42 days prior to initiation of IMFINZI in ADRIATIC was 14% (37/262) in patients receiving IMFINZI and 6% (16/265) in patients receiving placebo. Of the patients who received IMFINZI (262), 0.4% had a fatal adverse reaction and 2.7% had Grade 3 adverse reactions. Events resolved in 19 of the 37 (51%) patients and resulted in permanent discontinuation in 18 of the 37 (49%) patients. Systemic corticosteroids were required in all patients, while 1 patient required use of infliximab with high-dose steroids . IMFINZI with Tremelimumab-actl Immune-mediated pneumonitis occurred in 1.3% (5/388) of patients receiving IMFINZI in combination with tremelimumab-actl, including fatal (0.3%) and Grade 3 (0.2%) adverse reactions. Events resolved in 3 of the 5 patients and resulted in permanent discontinuation in 1 patient. Systemic corticosteroids were required in all patients; of these, 4 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). One patient (1/5) required other immunosuppressants. IMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy Immune-mediated pneumonitis occurred in 3.5% (21/596) of patients receiving IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy, including fatal (0.5%), and Grade 3 (1%) adverse reactions. Events resolved in 11 of the 21 patients and resulted in permanent discontinuation in 7 patients. Systemic corticosteroids were required in all patients with immune-mediated pneumonitis, while 1 patient (1/21) required other immunosuppressants. Immune-Mediated Colitis IMFINZI can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. IMFINZI as a Single Agent Immune-mediated colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (< 0.1%) and Grade 3 (0.4%) adverse reactions. Events resolved in 27 of the 37 patients and resulted in permanent discontinuation in 8 patients. Systemic corticosteroids were required in all patients with immune-mediated colitis, while 2 patients (2/37) required other immunosuppressants (e.g., infliximab, mycophenolate). IMFINZI with Tremelimumab-actl Immune-mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving IMFINZI in combination with tremelimumab-actl, including Grade 3 (3.6%) adverse reactions. Events resolved in 22 of the 23 patients and resulted in permanent discontinuation in 5 patients. All patients received systemic corticosteroids, and 20 of the 23 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Three patients also received other immunosuppressants. Intestinal perforation has been observed in other studies of IMFINZI in combination with tremelimumab-actl. IMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy Immune-mediated colitis occurred in 6.5% (39/596) of patients receiving IMFINZI in combination with tremelimumab-actl including fatal (0.2%) and Grade 3 (2.5%) adverse reactions. Events resolved in 33 of 39 patients and resulted in permanent discontinuation in 11 patients. Systemic corticosteroids were required in all patients with immune-mediated colitis, while 4 patients (4/39) required other corticosteroids. Intestinal perforation and large intestine perforation were reported in 0.1% of patients receiving IMFINZI in combination with tremelimumab-actl. Immune-Mediated Hepatitis IMFINZI can cause immune-mediated hepatitis. IMFINZI as a Single Agent Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions. Events resolved in 21 of the 52 patients and resulted in permanent discontinuation of IMFINZI in 6 patients. Systemic corticosteroids were required in all patients with immune-mediated hepatitis, while 2 patients (2/52) required use of mycophenolate with high-dose steroids. IMFINZI with Tremelimumab-actl Immune-mediated hepatitis occurred in 7.5% (29/388) of patients receiving IMFINZI in combination with tremelimumab-actl, including fatal (0.8%), Grade 4 (0.3%), and Grade 3 (4.1%) adverse reactions. Events resolved in 12 of the 29 patients and resulted in permanent discontinuation in 9 patients. Systemic corticosteroids were required in all 29 patients and all 29 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Eight patients (8/29) required other immunosuppressants. IMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy Immune-mediated hepatitis occurred in 3.9% (23/596) of patients receiving IMFINZI in combination with tremelimumab-actl, including fatal (0.3%), Grade 4 (0.5%), and Grade 3 (2.0%) adverse reactions. Events resolved in 12 of the 23 patients and resulted in permanent discontinuation in 10 patients. Systemic corticosteroids were required in all patients with immune-mediated hepatitis, while 2 patients (2/23) required use of other immunosuppressants. Immune-Mediated Endocrinopathies Adrenal Insufficiency IMFINZI can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold or permanently discontinue IMFINZI based on the severity [see Dosage and Administration (2.3) ] . IMFINZI as a Single Agent Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (< 0.1%) adverse reactions. Events resolved in 1 of the 9 patients and did not lead to permanent discontinuation of IMFINZI in any patients. Systemic corticosteroids were required in all patients with adrenal insufficiency; of these, the majority remained on systemic corticosteroids. IMFINZI with Tremelimumab-actl Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMFINZI in combination with tremelimumab-actl, including Grade 3 (0.3%) adverse reactions. Events resolved in 2 of the 6 patients. Systemic corticosteroids were required in all 6 patients, and of these, 1 patient required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). IMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy Immune-mediated adrenal insufficiency occurred in 2.2% (13/596) of patients receiving IMFINZI in combination with tremelimumab-actl, including Grade 3 (0.8%) adverse reactions. Events resolved in 2 of the 13 patients and resulted in permanent discontinuation in 1 patient. Systemic corticosteroids were required in all patients with adrenal insufficiency. One patient also required endocrine therapy. Hypophysitis IMFINZI can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated. Withhold or permanently discontinue IMFINZI depending on severity [see Dosage and Administration (2.3) ] . IMFINZI as a Single Agent Grade 3 hypophysitis/hypopituitarism occurred in < 0.1% (1/1889) of patients who received IMFINZI. Treatment with systemic corticosteroids was administered in this patient. The event did not lead to permanent discontinuation of IMFINZI. IMFINZI with Tremelimumab-actl Immune-mediated hypophysitis/hypopituitarism occurred in 1% (4/388) of patients receiving IMFINZI in combination with tremelimumab-actl. Events resolved in 2 of the 4 patients. Systemic corticosteroids were required in 3 patients, and of these, 1 patient received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Two patients also required endocrine therapy. IMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy Immune-mediated hypophysitis occurred in 1.3% (8/596) of patients receiving IMFINZI in combination with tremelimumab-actl, including Grade 3 (0.5%) adverse reactions. Events resulted in permanent discontinuation in 1 patient. Systemic corticosteroids were required in 6 patients with immune-mediated hypophysitis; of these, 2 of the 8 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Four patients also required endocrine therapy. Thyroid Disorders IMFINZI can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or discontinue IMFINZI based on the severity [see Dosage and Administration (2.3) ] . Thyroiditis IMFINZI as a Single Agent Immune-mediated thyroiditis occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (< 0.1%) adverse reactions. Events resolved in 4 of the 9 patients and resulted in permanent discontinuation in 1 patient. Systemic corticosteroids were required in 3 patients (3/9) with immune-mediated thyroiditis, while 8 patients (8/9) required endocrine therapy. IMFINZI with Tremelimumab-actl Immune-mediated thyroiditis occurred in 1.5% (6/388) of patients receiving IMFINZI in combination with tremelimumab-actl. Events resolved in 2 of the 6 patients. Systemic corticosteroids were required in 2 patients (2/6) with immune-mediated thyroiditis; of these, 1 patient required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). All patients required other therapy including hormone replacement therapy, thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker. IMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy Immune-mediated thyroiditis occurred in 1.2% (7/596) of patients receiving IMFINZI in combination with tremelimumab-actl. Events resolved in 2 of the 7 patients and one resulted in permanent discontinuation. Systemic corticosteroids were required in 2 patients (2/7) with immune-mediated thyroiditis, while all patients required endocrine therapy. Hyperthyroidism IMFINZI as a Single Agent Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of patients receiving IMFINZI. Events resolved in 30 of the 39 patients and did not lead to permanent discontinuation of IMFINZI in any patients. Systemic corticosteroids were required in 9 patients (9/39) with immune-mediated hyperthyroidism, while 35 patients (35/39) required endocrine therapy. IMFINZI with Tremelimumab-actl Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of patients receiving IMFINZI in combination with tremelimumab-actl, including Grade 3 (0.3%) adverse reactions. Events resolved in 15 of the 18 patients. Two patients (2/18) required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Seventeen patients required other therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker). IMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy Immune-mediated hyperthyroidism occurred in 5% (30/596) of patients receiving IMFINZI in combination with tremelimumab-actl, including Grade 3 (0.2%) adverse reactions. Events resolved in 21 of the 30 patients. Systemic corticosteroids were required in 5 patients (5/30) with immune-mediated hyperthyroidism, while 28 patients (28/30) required endocrine therapy. Hypothyroidism IMFINZI as a Single Agent Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. Events resolved in 31 of the 156 patients and did not lead to permanent discontinuation of IMFINZI in any patients. Systemic corticosteroids were required in 11 patients (11/156) and the majority of patients (152/156) required long-term thyroid hormone replacement. IMFINZI with Tremelimumab-actl Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving IMFINZI in combination with tremelimumab-actl. Events resolved in 5 of the 42 patients. One patient received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). All patients required other therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker). IMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy Immune-mediated hypothyroidism occurred in 8.6% (51/596) of patients receiving IMFINZI in combination with tremelimumab-actl, including Grade 3 (0.5%) adverse reactions. Systemic corticosteroids were required in 2 patients (2/51) and all patients required endocrine therapy. IMFINZI with Carboplatin and Paclitaxel Immune-mediated hypothyroidism occurred in 14% (34/235) of patients receiving IMFINZI in combination with carboplatin and paclitaxel. Events resolved in 8 of the 34 patients. Endocrine therapy was required in 34 of the 34 patients. Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue IMFINZI based on the severity [see Dosage and Administration (2.3) ]. IMFINZI as a Single Agent Grade 3 immune-mediated type 1 diabetes mellitus occurred in < 0.1% (1/1889) of patients receiving IMFINZI. This patient required long-term insulin therapy and IMFINZI was permanently discontinued. Two additional patients (0.1%, 2/1889) had events of hyperglycemia requiring insulin therapy that did not resolve at the time of reporting. IMFINZI with Tremelimumab-actl Two patients (0.5%, 2/388) had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up. IMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy Immune-mediated Type 1 diabetes mellitus occurred in 0.5% (3/596) of patients receiving IMFINZI in combination with tremelimumab-actl, including Grade 3 (0.3%) adverse reactions. All patients required endocrine therapy. Immune-Mediated Nephritis with Renal Dysfunction IMFINZI can cause immune-mediated nephritis. IMFINZI as a Single Agent Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (< 0.1%) adverse reactions. Events resolved in 5 of the 10 patients and resulted in permanent discontinuation in 3 patients. Systemic corticosteroids were required in all patients with immune-mediated nephritis. IMFINZI with Tremelimumab-actl Immune-mediated nephritis occurred in 1% (4/388) of patients receiving IMFINZI in combination with tremelimumab-actl, including Grade 3 (0.5%) adverse reactions. Events resolved in 3 of the 4 patients and resulted in permanent discontinuation in 2 patients. Systemic corticosteroids were required in all patients with immune-mediated nephritis; of these, 3 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). IMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy Immune-mediated nephritis occurred in 0.7% (4/596) of patients receiving IMFINZI in combination with tremelimumab-actl, including Grade 3 (0.2%) adverse reactions. Events resolved in 1 of the 4 patients and resulted in permanent discontinuation in 3 patients. Systemic corticosteroids were required in all patients with immune-mediated nephritis. Immune-Mediated Dermatology Reactions IMFINZI can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold or permanently discontinue IMFINZI depending on severity [see Dosage and Administration (2.3) ] . IMFINZI as a Single Agent Immune-mediated rash or dermatitis occurred in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions. Events resolved in 19 of the 34 patients and resulted in permanent discontinuation in 2 patients. Systemic corticosteroids were required in all patients with immune-mediated rash or dermatitis. IMFINZI with Tremelimumab-actl Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of patients receiving IMFINZI in combination with tremelimumab-actl, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions. Events resolved in 13 of the 19 patients and resulted in permanent discontinuation in 2 patients. Systemic corticosteroids were required in all patients with immune-mediated rash or dermatitis; of these, 12 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). One patient received other immunosuppressants. IMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy Immune-mediated rash or dermatitis occurred in 7.2% (43/596) of patients receiving IMFINZI in combination with tremelimumab-actl, including Grade 3 (0.3%) adverse reactions. Events resolved in 32 of the 43 patients and resulted in permanent discontinuation in 2 patients. Systemic corticosteroids were required in all patients with immune-mediated rash or dermatitis. Immune-Mediated Pancreatitis IMFINZI in combination with tremelimumab-actl can cause immune-mediated pancreatitis. IMFINZI with Tremelimumab-actl Immune-mediated pancreatitis occurred in 2.3% (9/388) of patients receiving IMFINZI in combination with tremelimumab-actl, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions. Events resolved in 6 of the 9 patients. Systemic corticosteroids were required in all 9 patients, and of these 7 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Other Immune-Mediated Adverse Reactions The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI or IMFINZI in combination with tremelimumab-actl, or were reported with the use of other PD-1/PD-L1 blocking antibodies. Cardiac/vascular: Myocarditis, pericarditis, vasculitis. Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy. Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss. Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis. Musculoskeletal and connective tissue disorders: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic. Endocrine: Hypoparathyroidism. Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection. 5.2 Infusion-Related Reactions IMFINZI can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI based on the severity [see Dosage and Administration (2.3) ] . For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. IMFINZI as a Single Agent Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions. IMFINZI in Combination with Tremelimumab-actl Infusion-related reactions occurred in 2.6% (10/388) of patients receiving IMFINZI in combination with tremelimumab-actl. IMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy Infusion-related reactions occurred in 2.9% (17/596) of patients receiving IMFINZI in combination with tremelimumab-actl, including Grade 3 (0.3%) adverse reactions. 5.3 Complications of Allogeneic HSCT after IMFINZI Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT. 5.4 Embryo-Fetal Toxicity Based on its mechanism of action and data from animal studies, IMFINZI can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of durvalumab to cynomolgus monkeys from the onset of organogenesis through delivery resulted in increased premature delivery, fetal loss and premature neonatal death. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMFINZI and for 3 months after the last dose of IMFINZI [see Use in Specific Populations (8.1 , 8.3 )] ."],"clinical_studies_table":["<table width=\"100%\"><caption>Table 26. Efficacy Results for the AEGEAN Study (mITT)</caption><col width=\"37%\"/><col width=\"31%\"/><col width=\"31%\"/><thead><tr><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><th align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><content styleCode=\"bold\">IMFINZI 1,500 mg every </content> <content styleCode=\"bold\">3 weeks with chemotherapy/ IMFINZI (N = 366)</content></th><th align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><content styleCode=\"bold\">Placebo with </content> <content styleCode=\"bold\">Chemotherapy/ Placebo (N = 374)</content></th></tr></thead><tbody><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">EFS</content><footnote ID=\"_Ref175053250\">Results are based on planned EFS interim analysis and pCR final analysis (DCO: 10 November 2022) which occurred 46.3 months after study initiation.</footnote></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Number of events, n (%)</item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>98 (27)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>138 (37)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Median EFS (95% CI) (months) </item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>NR (31.9, NR)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>25.9 (18.9, NR)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Hazard ratio (95% CI)</item></list></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.68 (0.53, 0.88)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>2-sided p-value<footnote ID=\"_Ref215061903\">Compared to a two-sided p-value boundary of 0.00989.</footnote><footnote ID=\"_Ref215061917\">The 2-sided p-value for pCR was calculated based on a stratified CMH test. The 2-sided p-value for EFS was calculated based on based on a stratified log-rank test. Stratification factors include PD-L1 and disease stage.</footnote></item></list></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.0039</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">pCR</content><footnoteRef IDREF=\"_Ref175053250\"/><content styleCode=\"bold\"><sup>, </sup></content><footnote ID=\"_Ref215142691\">Based on a pre-specified pCR interim analysis (DCO: 14 January 2022) in n = 402, the pCR rate was statistically significant (p = 0.000036) compared to significance level of 0.0082%.</footnote><content styleCode=\"bold\"><sup>, </sup></content><footnoteRef IDREF=\"_Ref215061917\"/></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Number of patients with response</item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>63</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>16</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>pCR rate, % (95% CI)</item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17.2 (13.5, 21.5)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.3 (2.5, 6.8)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>p-value</item></list></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>&lt; 0.0001</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Difference in proportions, % (95% CI) <footnote ID=\"_Ref215061961\">Confidence interval for the difference in proportions was calculated based on stratified Miettinen and Nurminen method.</footnote></item></list></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>13.0 (8.7, 17.6)</paragraph></td></tr></tbody></table>","<table cellpadding=\"0.35pt\" width=\"100.06%\"><caption>Table 27. Efficacy Results for the PACIFIC Study</caption><col width=\"53%\"/><col width=\"23%\"/><col width=\"23%\"/><thead><tr><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Endpoint</content></th><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">IMFINZI (N = 476)</content><footnote ID=\"_Ref165479210\">Among the ITT population, 7% in the IMFINZI arm and 10% in the placebo arm had non-measurable disease as assessed by BICR according to RECIST v1.1</footnote><content styleCode=\"bold\"/></th><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Placebo (N = 237)</content><footnoteRef IDREF=\"_Ref165479210\"/></th></tr><tr><th align=\"left\" colspan=\"3\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">Overall Survival (OS)</content><footnote ID=\"_Ref215062052\">OS results are based on the interim OS analysis conducted at 299 OS events which occurred 46 months after study initiation.</footnote><content styleCode=\"bold\"/></th></tr><tr><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">Number of deaths</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">183 (38%)</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">116 (49%)</th></tr><tr><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">Median in months (95% CI)</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">NR (34.7, NR) </th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">28.7 (22.9, NR)</th></tr><tr><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">Hazard Ratio (95% CI)<footnote ID=\"_Ref215062065\">Two-sided p-value based on a log-rank test stratified by sex, age, and smoking history</footnote></th><th align=\"left\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">0.68 (0.53, 0.87)</th></tr><tr><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">p-value<footnoteRef IDREF=\"_Ref215062065\"/><footnote ID=\"_Ref215062143\">Compared with allocated &#x3B1; of 0.00274 (Lan&#x2011;DeMets spending function approximating O&#x2019;Brien Fleming boundary) for interim analysis</footnote></th><th align=\"left\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">0.0025</th></tr></thead><tbody><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption><content styleCode=\"bold\">Progression-Free Survival (PFS)</content><footnote ID=\"_Ref215142818\">As assessed by BICR RECIST v1.1</footnote><footnote ID=\"_Ref215142835\">PFS results are based on the interim PFS analysis conducted at 371 PFS events which occurred 33 months after study initiation.</footnote></item></list></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Number (%) of patients with event</item></list></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>214 (45%)</item></list></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>157 (66%)</item></list></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Median in months (95% CI)</item></list></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>16.8 (13.0, 18.1)</item></list></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>5.6 (4.6, 7.8)</item></list></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Hazard Ratio (95% CI)<footnoteRef IDREF=\"_Ref215062065\"/><footnote ID=\"_Ref215142879\">Pike estimator</footnote></item></list></td><td colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>0.52 (0.42, 0.65)</item></list></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>p-value<footnoteRef IDREF=\"_Ref215062065\"/><footnote ID=\"_Ref215142983\">Compared with allocated &#x3B1; of 0.011035 (Lan&#x2011;DeMets spending function approximating O&#x2019;Brien Fleming boundary) for interim analysis</footnote></item></list></td><td colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>&lt; 0.0001</item></list></td></tr></tbody></table>","<table cellpadding=\"0pt\" width=\"99.32%\"><caption>Table 28. Efficacy Results for the POSEIDON Study</caption><col width=\"41%\"/><col width=\"30%\"/><col width=\"29%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td align=\"center\" styleCode=\"Rrule Botrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI with tremelimumab-actl and platinum-based chemotherapy (N = 338)</content> </paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Platinum-based chemotherapy</content> </paragraph><paragraph><content styleCode=\"bold\">(N = 337)</content> </paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">OS</content><footnote ID=\"_Ref119502626\">PFS/OS results are based on planned analyses which occurred 25/45 months respectively after study initiation. </footnote></paragraph></td><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"/></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Number of deaths (%) </item></list></td><td align=\"center\" styleCode=\"Rrule Botrule \" valign=\"top\"><paragraph>251 (74)</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule \" valign=\"top\"><paragraph>285 (85)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Median OS (months) </item><item><caption> </caption>(95% CI) </item></list></td><td align=\"center\" styleCode=\"Rrule Botrule \" valign=\"top\"><paragraph>14.0</paragraph><paragraph>(11.7, 16.1)</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule \" valign=\"top\"><paragraph>11.7</paragraph><paragraph>(10.5, 13.1)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>HR (95% CI) </item></list></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule \" valign=\"top\"><paragraph>0.77 (0.65, 0.92)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>p-value<footnote ID=\"_Ref119502876\">2-sided p-values based on log-rank tests stratified by PD-L1, histology and disease stage and compared to a boundary value of 0.00735 for PFS and 0.00797 for OS.</footnote><sup> </sup></item></list></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule \" valign=\"top\"><paragraph>0.00304</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">PFS</content><footnoteRef IDREF=\"_Ref119502876\"/></paragraph></td><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Number of events (%) </item></list></td><td align=\"center\" styleCode=\"Rrule Botrule \" valign=\"top\"><paragraph>238 (70)</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule \" valign=\"top\"><paragraph>258 (77)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Median PFS (months) </item><item><caption> </caption>(95% CI) </item></list></td><td align=\"center\" styleCode=\"Rrule Botrule \" valign=\"top\"><paragraph>6.2</paragraph><paragraph>(5.0, 6.5)</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule \" valign=\"top\"><paragraph>4.8</paragraph><paragraph>(4.6, 5.8)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>HR (95% CI) </item></list></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule \" valign=\"top\"><paragraph>0.72 (0.60, 0.86)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>p-value<footnoteRef IDREF=\"_Ref119502876\"/></item></list></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>0.00031</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">ORR % (95% CI)</content><footnote ID=\"_Ref215143567\">Confirmed responses with 95% Clopper-Pearson confidence interval.</footnote><content styleCode=\"bold\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule \" valign=\"top\"><paragraph> 39 (34, 44)</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule \" valign=\"top\"><paragraph>24 (20, 29)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Median DoR (months)</content> </paragraph><list listType=\"ordered\"><item><caption> </caption><content styleCode=\"bold\">(95% CI)</content> </item></list></td><td align=\"center\" styleCode=\"Rrule Toprule Botrule \" valign=\"top\"><paragraph>9.5</paragraph><paragraph>(7.2, NR)</paragraph></td><td align=\"center\" styleCode=\"Rrule Toprule Botrule \" valign=\"top\"><paragraph>5.1</paragraph><paragraph>(4.4, 6.0)</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Toprule \" valign=\"top\"/></tr></tbody></table>","<table styleCode=\"Noautorules\" width=\"100%\"><caption>Table 279. Efficacy Results for the ADRIATIC Study</caption><col width=\"31%\"/><col width=\"31%\"/><col width=\"38%\"/><thead><tr><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><th align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">IMFINZI</content> <content styleCode=\"bold\">(N=264)</content></th><th align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Placebo</content> <content styleCode=\"bold\">(N=266)</content></th></tr></thead><tbody><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">OS</content></paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Number of deaths (%)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>115 (44)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>146 (55)</paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Median OS (months) (95% CI)<footnote ID=\"_Ref184452876\">Calculated using the Kaplan Meier technique. CI for median derived based on Brookmeyer-Crowley method.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>55.9 (37.3, NR)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>33.4 (25.5, 39.9)</paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>HR (95% CI)<footnote ID=\"_Ref184453043\">Based on Cox proportional hazards model stratified by receipt of PCI.</footnote></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.73 (0.57, 0.93)</paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>p-value<footnote ID=\"_Ref184453057\">Compared with allocated alpha of 0.0168 for OS and 0.0280 for PFS (Lan&#x2011;DeMets spending function approximating O&#x2019;Brien Fleming boundary) for interim analysis.</footnote></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.0104</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">PFS</content><footnote ID=\"_Ref184453205\">Assessed by BICR according to RECIST v1.1.</footnote></paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Number of events (%)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>139 (53)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>169 (64)</paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Median PFS (months) (95% CI)<footnoteRef IDREF=\"_Ref184452876\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>16.6 (10.2, 28.2)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>9.2 (7.4, 12.9)</paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>HR (95% CI)<footnote ID=\"_Ref184453146\">Based on Cox proportional hazards model stratified by TNM stage and receipt of PCI.</footnote></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.76 (0.61, 0.95)</paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>p-value<footnoteRef IDREF=\"_Ref184453057\"/></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0.0161</paragraph></td></tr></tbody></table>","<table width=\"100%\"><caption>Table 30. OS Results for the CASPIAN Study</caption><col width=\"21%\"/><col width=\"45%\"/><col width=\"35%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Endpoint</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI with Etoposide and either Carboplatin or Cisplatin</content></paragraph><paragraph><content styleCode=\"bold\">(N = 268)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Etoposide and either Carboplatin or Cisplatin</content></paragraph><paragraph><content styleCode=\"bold\">(N = 269)</content></paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Overall Survival (OS)</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Number of deaths (%)<footnote ID=\"_Ref36637614\">At a pre-specified interim analysis, 336 OS events (79% of total planned events) were observed, and the boundary for declaring efficacy (0.0178) was determined by a Lan-Demets alpha spending function with O&#x2019;Brien Fleming type boundary.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>155 (58)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>181 (67)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Median OS (months) (95% CI)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>13.0 </paragraph><paragraph>(11.5, 14.8)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>10.3 </paragraph><paragraph>(9.3, 11.2)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hazard Ratio (95% CI)<footnote ID=\"_Ref215143874\">The analysis was performed using the stratified log-rank test, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin) and using the rank tests of association approach. </footnote></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>0.73 (0.59, 0.91)</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule \" valign=\"top\"><paragraph>p-value<footnoteRef IDREF=\"_Ref36637614\"/></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule \" valign=\"top\"><paragraph>0.0047</paragraph></td></tr></tbody></table>","<table styleCode=\"Noautorules\" width=\"100%\"><caption>Table 31. Efficacy Results for the TOPAZ-1 Study</caption><col width=\"41%\"/><col width=\"29%\"/><col width=\"30%\"/><thead><tr><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Endpoint</content></th><th align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">IMFINZI with Gemcitabine and Cisplatin</content> <content styleCode=\"bold\">(N = 341)</content></th><th align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Placebo with Gemcitabine and Cisplatin</content> <content styleCode=\"bold\">(N = 344)</content></th></tr></thead><tbody><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Overall Survival (OS)</content></paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Number of deaths (%)</item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>198 (58)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>226 (66)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Median OS (months) </item><item><caption> </caption>(95% CI)<footnote ID=\"_Ref112664054\">Kaplan-Meier estimated median with 95% CI derived using Brookmeyer-Crowley method</footnote></item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>12.8 (11.1, 14)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11.5 (10.1, 12.5)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Hazard Ratio (95% CI)<footnote ID=\"_Ref112664208\">Based on Cox proportional hazards model stratified by disease status and primary tumor location</footnote><content styleCode=\"bold\"/></item></list></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.80 (0.66, 0.97)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>p-value<footnote ID=\"_Ref112664367\">2-sided p-value based on a stratified log-rank test compared with alpha boundary of 0.030</footnote></item></list></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.021</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Progression-Free Survival (PFS)</content></paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Number of patients with event (%)</item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>276 (81)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>297 (86)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Median in months (95% CI)<footnoteRef IDREF=\"_Ref112664054\"/></item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>7.2 (6.7, 7.4)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>5.7 (5.6, 6.7)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Hazard Ratio (95% CI)<footnoteRef IDREF=\"_Ref112664208\"/></item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.75 (0.63, 0.89)</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>p-value<footnote ID=\"_Ref112664322\">2-sided p-value based on a stratified log-rank test compared with alpha boundary of 0.048</footnote></item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.001</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/></tr><tr><td colspan=\"3\" valign=\"top\"/></tr></tbody></table>","<table width=\"98.42%\"><caption>Table 32. Efficacy Results for the HIMALAYA Study</caption><col width=\"47%\"/><col width=\"26%\"/><col width=\"27%\"/><thead><tr><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Endpoint</content></th><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">IMFINZI and Tremelimumab-actl</content> <content styleCode=\"bold\">(N = 393)</content></th><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Sorafenib</content> <content styleCode=\"bold\">(N = 389)</content></th></tr></thead><tbody><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">OS</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Number of deaths (%)</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>262 (66.7)</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>293 (75.3)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Median OS (months)</paragraph><paragraph>(95% CI)</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>16.4</paragraph><paragraph>(14.2, 19.6)</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13.8</paragraph><paragraph>(12.3, 16.1)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>HR (95% CI)<footnote ID=\"_Ref117768774\">HR (IMFINZI and tremelimumab-actl vs. sorafenib) based on the stratified Cox proportional hazard model.</footnote></paragraph></td><td colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.78 (0.66, 0.92)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>p-value<footnote ID=\"_Ref117768787\">Based on a stratified log-rank test.</footnote><footnote ID=\"_Ref117768796\">Based on a Lan-DeMets alpha spending function with O&apos;Brien Fleming type boundary and the actual number of events observed, the boundary for declaring statistical significance for IMFINZI and tremelimumab-actl vs. sorafenib was 0.0398 (Lan and DeMets 1983).</footnote></paragraph></td><td colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.0035</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">PFS</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Number of events (%)</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>335 (85.2)</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>327 (84.1)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Median in (months) </paragraph><paragraph>(95% CI)</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.8 </paragraph><paragraph>(3.7, 5.3)</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.1 </paragraph><paragraph>(3.7, 5.5)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>HR (95% CI)<footnoteRef IDREF=\"_Ref117768774\"/></paragraph></td><td colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.90 (0.77, 1.05)</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">ORR</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>ORR % (95% CI)<footnote ID=\"_Ref119566644\">Confirmed complete response or partial response.</footnote><footnote ID=\"_Ref117769788\">Based on Clopper-Pearson method.</footnote></paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>20.1 (16.3, 24.4)</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>5.1 (3.2, 7.8)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Complete Response n (%)</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>12 (3.1)</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0 </paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Partial Response n (%)</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>67 (17.0)</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>20 (5.1)</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>DoR</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Median DoR (months) (95% CI)</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>22.3 (13.7, NR)</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>18.4 (6.5, 26.0)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>% with duration &#x2265; 6 months</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>82.3</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>78.9</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>% with duration &#x2265; 12 months</paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>65.8</paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>63.2</paragraph></td></tr></tbody></table>","<table cellpadding=\"0pt\" width=\"100%\"><caption>Table 33. Efficacy Results for Patients with dMMR Tumors in the DUO-E Study</caption><col width=\"48%\"/><col width=\"26%\"/><col width=\"26%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">Endpoint</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI with Carboplatin and Paclitaxel</content></paragraph><paragraph><content styleCode=\"bold\">N=46</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Carboplatin and Paclitaxel</content></paragraph><paragraph><content styleCode=\"bold\">N=49</content></paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph><content styleCode=\"bold\"> PFS</content><footnote ID=\"_Ref175233274\">Investigator assessed.</footnote></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><list listType=\"ordered\"><item><caption> </caption>Number of events (%)</item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>15 (32.6)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>25 (51.0)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><list listType=\"ordered\"><item><caption> </caption>Median in months (95% CI)<footnote ID=\"_Ref194390767\">Calculated using the Kaplan-Meier technique.</footnote></item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>NR </paragraph><paragraph>(NR, NR)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>7.0 </paragraph><paragraph>(6.7, 14.8)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><list listType=\"ordered\"><item><caption> </caption>HR (95% CI)</item></list></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>0.42 (0.22, 0.80)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\"> ORR</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">N=42</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">N=42</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>ORR % (95% CI)</item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>71.4</paragraph><paragraph>(55.4, 84.3)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>40.5</paragraph><paragraph>(25.6, 56.7)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Complete response %</item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>12 (28.6)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>4 (9.5)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Partial response</item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>18 (42.9)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>13 (31.0)</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\"> DOR</content></paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph> Median in months (range)</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>NR</paragraph><paragraph>(2.4+, 26.9+)</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>10.5</paragraph><paragraph>(2.1+, 25.2+)</paragraph></td></tr></tbody></table>","<table styleCode=\"Noautorules\" width=\"100%\"><caption>Table 34. Efficacy Results for the NIAGARA Study</caption><col width=\"33%\"/><col width=\"33%\"/><col width=\"33%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI plus gemcitabine and cisplatin</content></paragraph><paragraph><content styleCode=\"bold\">(N=533)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Gemcitabine and cisplatin</content></paragraph><paragraph><content styleCode=\"bold\">(N = 530)</content></paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">EFS</content><footnote ID=\"_Ref194400348\">EFS is defined as the time from randomization to the first recurrence of disease after radical cystectomy, the time of first documented progression in patients who are medically precluded from a radical cystectomy, or time of expected surgery in patients who refuse to undergo a radical cystectomy or failure to undergo a radical cystectomy in participants with residual disease, or the time of death due to any cause, whichever occurs first.</footnote></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph> Number of events (%)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>187. (35.1)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>246 (46.4)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph> Median EFS (months) (95% CI)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>NR (NR, NR)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>46.1 (32.2, NR)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph> HR (95% CI)<footnote ID=\"_Ref194400368\">Based on stratified Cox proportional hazard model.</footnote></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.68 (0.56, 0.82)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph> 2-sided p-value<footnote ID=\"_Ref194400386\">Based on stratified log-rank test.</footnote><sup>,</sup><footnote ID=\"_Ref194400489\">Alpha allocated at the interim analysis was 0.0412 for EFS and 0.0154 for OS.</footnote></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>&lt;0.0001</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Overall Survival (OS)</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph> Number of events (%)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>136.(25.5)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>169 (31.9</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph> Median OS (months) (95% CI)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>NR (NR, NR)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>NR (NR, NR)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph> HR (95% CI)<footnoteRef IDREF=\"_Ref194400368\"/></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.75 (0.59, 0.93)</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph> 2-sided p-value<footnoteRef IDREF=\"_Ref194400386\"/><sup>,</sup><footnoteRef IDREF=\"_Ref194400489\"/></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0.0106</paragraph></td></tr></tbody></table>","<table width=\"100.04%\"><caption>Table 35. Efficacy Results for the MATTERHORN Study</caption><col width=\"50%\"/><col width=\"28%\"/><col width=\"23%\"/><thead><tr><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><th align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><content styleCode=\"bold\">IMFINZI + FLOT chemotherapy (N = 474)</content></th><th align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><content styleCode=\"bold\">Placebo + FLOT chemotherapy (N = 474)</content></th></tr></thead><tbody><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Event Free Survival (EFS)</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Number of events, n (%)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>167 (35)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>218 (46)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Median EFS (months) (95% CI)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>NR (40.7, NE)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>32.8 (27.9, NE)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>HR (95% CI)</paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.71 (0.58, 0.86)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>p-value</paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>&lt;0.001</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Overall Survival (OS)</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Number of events (%)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>160 (33.8)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>192 (40.5)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Median OS (months) (95% CI)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>NR (NE, NE)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>NR (NE, NE)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>HR (95% CI)</paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.78 (0.63, 0.96)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>p-value</paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.021</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">pCR</content><footnote ID=\"_Ref215144955\">Results for EFS are based on a pre-specified interim analysis (DCO: 20 December 2024), results for OS are based on a pre-specified final analysis (DCO: 01 September 2025), and results for pCR are based on a pre-specified final analysis (DCO: 01 February 2023).</footnote></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Number of patients with response</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>91</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>34</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Response rate, (%) (95% CI)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>19.2 (15.7, 23.0)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>7.2 (5.0, 9.9)</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>p-value</paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>&lt;0.001</paragraph></td></tr></tbody></table>"],"nonclinical_toxicology":["13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenic and genotoxic potential of durvalumab have not been evaluated. Animal fertility studies have not been conducted with durvalumab. In repeat-dose toxicology studies with durvalumab in sexually mature cynomolgus monkeys of up to 3 months duration, there were no notable effects on the male and female reproductive organs. 13.2 Animal Toxicology and/or Pharmacology In animal models, inhibition of PD-L1/PD-1 signaling increased the severity of some infections and enhanced inflammatory responses. Mycobacterium tuberculosis -infected PD-1 knockout mice exhibit markedly decreased survival compared with wild-type controls, which correlated with increased bacterial proliferation and inflammatory responses in these animals. PD-1 blockade using a primate anti-PD-1 antibody was also shown to exacerbate M. tuberculosis infection in rhesus macaques. PD-L1 and PD-1 knockout mice and mice receiving PD-L1 blocking antibody have also shown decreased survival following infection with lymphocytic choriomeningitis virus."],"adverse_reactions_table":["<table styleCode=\"Noautorules\" width=\"100%\"><caption>Table 5. Adverse Reactions Occurring in &#x2265; 10% of Patients in the AEGEAN Study</caption><col width=\"31%\"/><col width=\"17%\"/><col width=\"17%\"/><col width=\"17%\"/><col width=\"17%\"/><tbody><tr><td rowspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Adverse Reaction</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI with Chemotherapy</content></paragraph><paragraph><content styleCode=\"bold\">N=401</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Placebo with Chemotherapy</content></paragraph><paragraph><content styleCode=\"bold\">N=398</content></paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3 or 4 (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3 or 4 (%)</content></paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Gastrointestinal disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Nausea</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>25</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>29</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Constipation</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>25</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>21</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Diarrhea<footnote ID=\"_Ref175042679\">includes colitis, diarrhea, enteritis, and proctitis.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>14</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.3 </paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Vomiting</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.7</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">General disorders and administration site conditions</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Fatigue<footnote ID=\"_Ref175042700\">includes fatigue and asthenia.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>25</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>25</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Skin and subcutaneous tissue disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Rash<footnote ID=\"_Ref175042723\">includes dermatitis, dermatitis acneiform, drug eruption, eczema, eczema asteatotic, erythema, palmar&#x2011;erythrodysaesthesia syndrome, pemphigoid, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, and rash pustular, skin exfoliation, and urticarial dermatitis.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>22</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>14</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pruritus</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>12</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Musculoskeletal and connective tissue disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Musculoskeletal pain<footnote ID=\"_Ref175042752\">includes arthralgia, arthritis, back pain, bone pain, chest pain, musculoskeletal chest pain, musculoskeletal pain, musculoskeletal discomfort, musculoskeletal stiffness,myalgia, neck pain, non-cardiac chest pain, pain in extremity, and spinal pain.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>24</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>29</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.5</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased appetite</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>18</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>18</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.3</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Nervous system disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Peripheral neuropathy<footnote ID=\"_Ref175042779\">includes dysaesthesia, hypoaesthesia, neuralgia, neuropathy peripheral, paraesthesia, peripheral sensory neuropathy, and polyneuropathy.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>16</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>22</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Endocrine disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypothyroidism<footnote ID=\"_Ref175042813\">includes blood thyroid stimulating hormone increased and hypothyroidism.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Respiratory, thoracic and mediastinal disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Cough / Productive cough</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pneumonia<footnote ID=\"_Ref175042838\">includes lower respiratory tract infection, lung abscess, paracancerous pneumonia, pneumonia, pneumonia aspiration, pneumonia bacterial, pneumonia chlamydial, pneumonia cryptococcal, pneumonia fungal, pneumonia pseudomonal, pneumonia streptococcal, pneumonia viral, and post-procedural pneumonia.</footnote><sup>, </sup><footnote ID=\"_Ref175042854\">Five Grade 5 events in the IMFINZI arm and four Grade 5 events in the Placebo arm.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>COVID-19<footnote ID=\"_Ref175042875\">Includes COVID-19 and COVID-19 Pneumonia. Five Grade 5 events in the IMFINZI arm and One Grade 5 event in the placebo arm.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Psychiatric Disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Insomnia</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>12</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0</paragraph></td></tr></tbody></table>","<table styleCode=\"Noautorules\" width=\"100%\"><caption>Table 6. Select Laboratory Abnormalities (&#x2265;20%) That Worsened from Baseline in Patients with Disease Who Received IMFINZI with Chemotherapy in AEGEAN</caption><col width=\"47%\"/><col width=\"14%\"/><col width=\"12%\"/><col width=\"14%\"/><col width=\"13%\"/><tbody><tr><td rowspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Laboratory Abnormality</content><footnote ID=\"_Ref175045667\">Graded per NCI CTCAE V5.</footnote></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI with Chemotherapy<footnote ID=\"_Ref175045753\">The denominator used to calculate the rate varied from 349 to 399 based on the number of patients with a baseline value and at least one post-treatment value.</footnote></content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Placebo with </content></paragraph><paragraph><content styleCode=\"bold\">Chemotherapy<footnote ID=\"_Ref175045776\">The denominator used to calculate the rate varied from 333 to 398 based on the number of patients with a baseline value and at least one post-treatment value.</footnote></content></paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade </content></paragraph><paragraph><content styleCode=\"bold\">3 or 4</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All</content></paragraph><paragraph><content styleCode=\"bold\">Grades</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade </content></paragraph><paragraph><content styleCode=\"bold\">3 or 4</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Hematology</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hemoglobin decreased </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>78</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>75</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>9</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Leukocytes decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>63</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>12</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>64</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Neutrophils decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>52</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>24</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>56</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>27</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Platelets decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>46</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>7</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>44</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Lymphocytes decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>41</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>37</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>9</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Chemistry</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Calcium corrected, decreased </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>51</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>52</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.5</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Alanine aminotransferase increased </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>49</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>42</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Aspartate aminotransferase increased </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>47</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>37</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.8</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Potassium increased </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>33</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>29</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Sodium decreased </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>35</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>33</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Gamma glutamyl transferase increased </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>36</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.7</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>35</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.1</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Creatinine increased </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>32</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>27</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Amylase increased </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>25</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.7</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>24</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Magnesium decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>22</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>20</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.6</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Lipase increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>23</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>4.9</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>24</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>7</paragraph></td></tr></tbody></table>","<table width=\"100.1%\"><caption>Table 7. Adverse Reactions Occurring in &#x2265; 10% of Patients in the PACIFIC Study</caption><col width=\"34%\"/><col width=\"17%\"/><col width=\"17%\"/><col width=\"17%\"/><col width=\"17%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI </content></paragraph><paragraph><content styleCode=\"bold\">N = 475</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Placebo</content></paragraph><paragraph><content styleCode=\"bold\">N = 234</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">Adverse Reaction</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">All Grades</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">Grades 3-4 </content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">All Grades</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">Grades 3-4 </content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Respiratory, Thoracic, and Mediastinal Disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Cough/Productive Cough</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>40</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>30</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.4</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pneumonitis<footnote ID=\"_Ref184450926\">Includes acute interstitial pneumonitis, interstitial lung disease, pneumonitis, pulmonary fibrosis.</footnote>/Radiation Pneumonitis<sup/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>34</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>25</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Dyspnea<footnote ID=\"_Ref184451090\">Includes dyspnea, and exertional dyspnea.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>25</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>25</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.6</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">General Disorders </content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Fatigue<footnote ID=\"_Ref184451417\">Includes asthenia and fatigue.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>34</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>32</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pyrexia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>15</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Infections </content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Upper respiratory tract infections<footnote ID=\"_Ref184451392\">Includes laryngitis, nasopharyngitis, peritonsillar abscess, pharyngitis, rhinitis, sinusitis, tonsillitis, tracheobronchitis, and upper respiratory tract infection.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>26</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>19</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pneumonia<footnote ID=\"_Ref184451356\">Includes lung infection, pneumocystis jirovecii pneumonia, pneumonia, pneumonia adenoviral, pneumonia bacterial, pneumonia cytomegaloviral, pneumonia haemophilus, pneumonia klebsiella, pneumonia necrotizing, pneumonia pneumococcal, and pneumonia streptococcal.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>7</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>12</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Skin and Subcutaneous Tissue Disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Rash<footnote ID=\"_Ref184451337\">Includes rash erythematous, rash generalized, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, erythema, eczema, rash, and dermatitis.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>23</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>12</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pruritus<footnote ID=\"_Ref184451313\">Includes pruritus generalized and pruritus.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>12</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Gastrointestinal Disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Diarrhea</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>18</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>19</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Abdominal pain<footnote ID=\"_Ref184451297\">Includes abdominal pain, abdominal pain lower, abdominal pain upper, and flank pain.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.4</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Endocrine Disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Hypothyroidism<footnote ID=\"_Ref184451279\">Includes autoimmune hypothyroidism and hypothyroidism.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>12</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>1.7</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0</paragraph></td></tr></tbody></table>","<table styleCode=\"Noautorules\" width=\"100%\"><caption>Table 8. Laboratory Abnormalities Worsening from Baseline Occurring in &#x2265; 20% of Patients in the PACIFIC Study</caption><col width=\"34%\"/><col width=\"17%\"/><col width=\"17%\"/><col width=\"17%\"/><col width=\"17%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Placebo</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Laboratory Abnormality</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades</content><footnote ID=\"_Ref215752907\">Graded according to NCI CTCAE version 4.0.</footnote></paragraph><paragraph><content styleCode=\"bold\">(%)</content><footnote ID=\"_Ref215062707\">Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI (range: 464 to 470) and placebo (range: 224 to 228).</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3 or 4</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades</content><footnoteRef IDREF=\"_Ref215752907\"/></paragraph><paragraph><content styleCode=\"bold\">(%)</content><footnoteRef IDREF=\"_Ref215062707\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3 or 4</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Chemistry</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hyperglycemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>52</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>51</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypocalcemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>46</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>41</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased ALT</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>39</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>22</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.4</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased AST</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>36</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>21</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.4</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hyponatremia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>33</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>30</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.1</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hyperkalemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>32</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.1</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>29</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.8</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased GGT</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>24</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>22</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.7</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Hematology</content></paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Lymphopenia</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><paragraph>43 </paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><paragraph>17 </paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><paragraph>39 </paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><paragraph>18 </paragraph></td></tr></tbody></table>","<table width=\"100%\"><caption>Table 9. Adverse Reactions (&#x2265; 10%) in Patients with NSCLC Who Received IMFINZI in the POSEIDON Study</caption><col width=\"28%\"/><col width=\"17%\"/><col width=\"19%\"/><col width=\"18%\"/><col width=\"18%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"/><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">IMFINZI with tremelimumab-actl and platinum-based chemotherapy </content></paragraph><paragraph><content styleCode=\"bold\">N = 330</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Platinum-based chemotherapy</content></paragraph><paragraph><content styleCode=\"bold\">N = 333</content></paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Adverse Reaction</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3 or 4 (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3 or 4 (%)</content></paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Gastrointestinal disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Nausea</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>42</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>37</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.1</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Diarrhea</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>22</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>15</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Constipation</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>19</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>24</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Vomiting</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>18</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>14</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Stomatitis<footnote ID=\"_Ref170197581\">Includes mucosal inflammation and stomatitis.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.3</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">General disorders and administration site conditions</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Fatigue/Asthenia<footnote ID=\"_Ref170198865\">Includes asthenia and fatigue.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>36</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>32</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.5</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pyrexia<footnote ID=\"_Ref170198903\">Includes body temperature increased, hyperpyrexia, hyperthermia, and pyrexia.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>19</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Edema<footnote ID=\"_Ref170199023\">Includes face edema, localized edema, and edema peripheral.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.6</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Musculoskeletal and connective tissue disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Musculoskeletal Pain<footnote ID=\"_Ref170199052\">Includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, and spinal pain.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>29</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>22</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased appetite</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>28</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>25</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.2</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Skin and subcutaneous tissue disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Rash<footnote ID=\"_Ref170199084\">Includes eczema, erythema, dermatitis, drug eruption, erythema multiforme, pemphigoid, rash, rash maculo-papular, rash papular, rash pruritic, and rash pustular.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>27</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pruritus</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Alopecia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Infections and Infestations</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pneumonia<footnote ID=\"_Ref170199118\">Includes lower respiratory tract infection, pneumocystis jirovecii pneumonia, pneumonia, pneumonia aspiration, and pneumonia bacterial.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>12</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.2</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Upper respiratory tract infections<footnote ID=\"_Ref170199136\">Includes laryngitis, nasopharyngitis, pharyngitis, rhinitis, sinusitis, tonsillitis, tracheobronchitis and upper respiratory tract infection.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>15</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.9</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Endocrine disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypothyroidism<footnote ID=\"_Ref170199174\">Includes blood thyroid stimulating hormone increased and hypothyroidism.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.1</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Respiratory, thoracic and mediastinal disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Cough/Productive Cough<footnote ID=\"_Ref170199203\">Includes cough and productive cough.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>12</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.3</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Nervous system disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Headache<footnote ID=\"_Ref170199216\">Includes headache and migraine.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>8</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0.6</paragraph></td></tr></tbody></table>","<table styleCode=\"Noautorules\" width=\"539.75pt\"><caption>Table 10. Select Laboratory Abnormalities (&#x2265; 10%) That Worsened from Baseline in Patients with NSCLC Who Received IMFINZI in the POSEIDON Study</caption><col width=\"27%\"/><col width=\"18%\"/><col width=\"18%\"/><col width=\"18%\"/><col width=\"18%\"/><tbody><tr><td rowspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Laboratory Abnormality</content><footnote ID=\"_Ref170199952\">Graded according to NCI CTCAE version 4.03.</footnote></paragraph></td><td colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI with tremelimumab-actl and platinum-based chemotherapy<footnote ID=\"_Ref170200030\">The denominator used to calculate the rate varied from 45 to 326 based on the number of patients with a baseline value and at least one post-treatment value.</footnote></content></paragraph></td><td colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Platinum-based chemotherapy<footnote ID=\"_Ref170200050\">The denominator used to calculate the rate varied from 43 to 323 based on the number of patients with a baseline value and at least one post-treatment value.</footnote></content></paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3 or 4</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3 or 4</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Chemistry</content></paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Blood creatinine increased </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>89</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>83</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.9</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased ALT</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>64</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>56</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.7</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased AST</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>63</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>55</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.2</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypocalcemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>58</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>49</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.9</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hyponatremia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>55</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>50</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hyperkalemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>49</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>35</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.8</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hyperglycemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>42</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>37</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.1</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Amylase increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>41</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>25</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Gamma Glutamyl Transferase increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>38</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>35</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.7</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Lipase increased </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>35</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>14</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>25</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>5</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased Alkaline Phosphatase</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>33</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>26</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.2</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Albumin decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>27</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>18</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.9</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypokalemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>21</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>7</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.8</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Bilirubinemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>16</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypernatremia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>15</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>14</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypomagnesemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>12</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>23</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Hematology</content></paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Anemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>84</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>24</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>84</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>25</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Leukopenia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>77</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>21</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>81</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>18</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Neutropenia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>71</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>37</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>69</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>32</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Lymphocytopenia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>67</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>20</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>60</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>19</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Thrombocytopenia</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>53</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>54</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>12</paragraph></td></tr></tbody></table>","<table width=\"100%\"><caption>Table 11. Adverse Reactions (&#x2265; 10%) in Patients with LS-SCLC Who Received IMFINZI in the ADRIATIC Study</caption><col width=\"40%\"/><col width=\"15%\"/><col width=\"15%\"/><col width=\"13%\"/><col width=\"17%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI</content></paragraph><paragraph><content styleCode=\"bold\">(N=262)</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Placebo</content></paragraph><paragraph><content styleCode=\"bold\">(N=265)</content></paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Adverse Reaction</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3 or 4</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3 or 4</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Respiratory, thoracic and mediastinal disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pneumonitis or Radiation pneumonitis<footnote ID=\"_Ref184377955\">Includes pneumonitis, immune-mediated lung disease, interstitial lung disease, radiation pneumonitis, and lung radiation fibrosis</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>38</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.1</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>30</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Cough/Productive cough</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>14</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Dyspnea<footnote ID=\"_Ref184378404\">Includes dyspnea and exertional dyspnea.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>7</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">General disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Fatigue<footnote ID=\"_Ref184378464\">Includes fatigue and asthenia.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>21</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>20</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Skin and subcutaneous tissue disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Rash<footnote ID=\"_Ref184378505\">Includes dermatitis, acneiform dermatitis, eczema, rash, maculo-papular rash, papular rash, pruritic rash, and skin exfoliation.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>18</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pruritus</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>7</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Endocrine disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypothyroidism<footnote ID=\"_Ref184378626\">Includes hypothyroidism, increased blood thyroid stimulating hormone, and decreased thyroxine free.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hyperthyroidism<footnote ID=\"_Ref184378644\">Includes hyperthyroidism, decreased blood thyroid stimulating hormone, increased thyroxine free, increased thyroxine, increased tri-iodothyronine free, and increased tri-iodothyronine.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>12</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased appetite</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Nervous system disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Dizziness<footnote ID=\"_Ref184378662\">Includes dizziness, postural dizziness, vertigo, and positional vertigo.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>14</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Infections and infestations</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pneumonia<footnote ID=\"_Ref184378675\">Includes pneumonia, atypical pneumonia, lower respiratory tract infection, bacterial pneumonia, pneumocystis jirovecii pneumonia, legionella pneumonia, and viral pneumonia.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.1</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.2</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Gastrointestinal disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Nausea</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Diarrhea</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Constipation</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0</paragraph></td></tr></tbody></table>","<table styleCode=\"Noautorules\" width=\"100%\"><caption>Table 12. Select Laboratory Abnormalities (&#x2265; 20%) That Worsened from Baseline in Patients with LS-SCLC Who Received IMFINZI in the ADRIATIC Study</caption><col width=\"41%\"/><col width=\"15%\"/><col width=\"15%\"/><col width=\"14%\"/><col width=\"15%\"/><tbody><tr><td rowspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Laboratory Abnormality</content><footnote ID=\"_Ref184378831\">Graded according to NCI CTCAE version 4.03, except creatinine increased which is graded according to NCI CTCAE version 5.0.</footnote></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI</content><footnote ID=\"_Ref184378960\">The denominator used to calculate the rate varied from 63 to 259 based on the number of patients with a baseline value and at least one post-treatment value.</footnote></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Placebo</content><footnote ID=\"_Ref184378974\">The denominator used to calculate the rate varied from 65 to 262 based on the number of patients with a baseline value and at least one post-treatment value.</footnote></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption><content styleCode=\"bold\">All Grades</content></item><item><caption> </caption><content styleCode=\"bold\">(%)</content></item></list></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption><content styleCode=\"bold\">Grade 3 or 4</content></item><item><caption> </caption><content styleCode=\"bold\">(%)</content></item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades </content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3 or 4</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Chemistry</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypocalcemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>43</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>43</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hyperglycemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>38</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>45</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>ALT increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>36</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>29</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>AST increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>33</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>28</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Gamma Glutamyl Transferase increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>32</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>7</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>27</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.9</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hyponatremia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>32</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>29</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6.2</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hyperkalemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>23</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Creatinine increased<footnoteRef IDREF=\"_Ref184378831\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>21</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Hematology</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Lymphocytes decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>34</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>33</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Leukocytes decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>26</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>33</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>1.1</paragraph></td></tr></tbody></table>","<table width=\"100%\"><caption>Table 13. Adverse Reactions Occurring in &#x2265; 10% of Patients in the CASPIAN Study</caption><col width=\"26%\"/><col width=\"19%\"/><col width=\"19%\"/><col width=\"18%\"/><col width=\"18%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"/><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">IMFINZI with etoposide and either carboplatin or cisplatin </content></paragraph><paragraph><content styleCode=\"bold\">N = 265</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">Etoposide and either carboplatin or cisplatin </content></paragraph><paragraph><content styleCode=\"bold\">N = 266</content></paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Adverse Reaction</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3-4 (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3-4 (%)</content></paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Gastrointestinal disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Nausea</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>34</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>34</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.9</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Constipation</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>19</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Vomiting</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>15</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.1</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Diarrhea</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.1</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.1</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">General disorders and administration site conditions</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Fatigue/Asthenia </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>32</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>32</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Skin and subcutaneous tissue disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Alopecia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>31</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.1</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>34</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Rash<footnote ID=\"_Ref184389101\">Includes rash erythematous, rash generalized, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, erythema, eczema, rash and dermatitis.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased appetite</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>18</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Respiratory, thoracic and mediastinal disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Cough/Productive Cough</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>15</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Endocrine disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Hyperthyroidism<footnote ID=\"_Ref184389163\">Includes hyperthyroidism and Basedow&apos;s disease.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0</paragraph></td></tr></tbody></table>","<table width=\"99.92%\"><caption>Table 14. Laboratory Abnormalities Worsening from Baseline Occurring in &#x2265; 20%<footnote ID=\"_Ref184390039\">The frequency cut off is based on any grade change from baseline.</footnote> of Patients in the CASPIAN Study</caption><col width=\"47%\"/><col width=\"28%\"/><col width=\"25%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI with Etoposide and either Carboplatin or Cisplatin </content></paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Etoposide and either Carboplatin or Cisplatin </content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Laboratory Abnormality</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade</content><footnote ID=\"_Ref184390235\">Graded according to NCI CTCAE version 4.03.</footnote><content styleCode=\"bold\"> 3 or 4 (%)</content><footnote ID=\"_Ref184390198\">Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI (range: 258 to 263) and chemotherapy (range: 253 to 262) except magnesium IMFINZI with chemotherapy (18) and chemotherapy (16).</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade</content><footnoteRef IDREF=\"_Ref184390235\"/><content styleCode=\"bold\"> 3 or 4 (%)</content><footnoteRef IDREF=\"_Ref184390198\"/></paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Chemistry</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hyponatremia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypomagnesemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hyperglycemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>5</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased Alkaline Phosphatase</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.5</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased ALT</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.7</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased AST</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.2</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypocalcemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.4</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Blood creatinine increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.1</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hyperkalemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.1</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>TSH decreased &lt; LLN<footnote ID=\"_Ref184390287\">LLN = lower limit of normal.</footnote> and &#x2265; LLN at baseline</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>NA</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>NA</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Hematology</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Neutropenia </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>41</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>48</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Lymphopenia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>14</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Anemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>22</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Thrombocytopenia</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>12</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>15</paragraph></td></tr></tbody></table>","<table width=\"100%\"><caption>Table 15. Adverse Reactions Occurring in &#x2265; 10% of Patients in the TOPAZ-1 Study</caption><col width=\"24%\"/><col width=\"20%\"/><col width=\"18%\"/><col width=\"19%\"/><col width=\"18%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"/><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">IMFINZI with Gemcitabine and Cisplatin </content></paragraph><paragraph><content styleCode=\"bold\">N = 338</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">Placebo with Gemcitabine and Cisplatin </content></paragraph><paragraph><content styleCode=\"bold\">N = 342</content></paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Adverse Reaction</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades</content><footnote ID=\"_Ref184390489\">Graded according to NCI CTCAE version 5.0.</footnote><content styleCode=\"bold\"> (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade</content><footnoteRef IDREF=\"_Ref184390489\"/><content styleCode=\"bold\"> 3-4 (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades</content><footnoteRef IDREF=\"_Ref184390489\"/><content styleCode=\"bold\"> (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade</content><footnoteRef IDREF=\"_Ref184390489\"/><content styleCode=\"bold\"> 3-4 (%)</content></paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">General disorders and administration site conditions</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Fatigue<footnote ID=\"_Ref184390688\">Includes fatigue, malaise, cancer fatigue and asthenia.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>42</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>43</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pyrexia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>20</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>16</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.6</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Gastrointestinal disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Nausea</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>40</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>34</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.8</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Constipation</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>32</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>29</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Abdominal pain<footnote ID=\"_Ref184390714\">Includes abdominal pain, abdominal pain lower, abdominal pain upper and flank pain.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>24</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>23</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.9</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Vomiting</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>18</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>18</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Diarrhea</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>15</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.8</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased appetite</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>26</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.1</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>23</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.9</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Skin and subcutaneous tissue disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Rash<footnote ID=\"_Ref184390746\">Includes rash macular, rash maculopapular, rash morbilliform, rash papular, rash pruritic, rash pustular, rash erythematous, dermatitis acneiform, dermatitis bullous, drug eruption, eczema, erythema, dermatitis and rash.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>23</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>14</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pruritus</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Psychiatric disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Insomnia</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0</paragraph></td></tr></tbody></table>","<table width=\"99.92%\"><caption>Table 16. Laboratory Abnormalities Worsening from Baseline Occurring in &#x2265; 20%<footnote ID=\"_Ref184390922\">The frequency cut off is based on any grade change from baseline.</footnote> of Patients in the TOPAZ-1 Study</caption><col width=\"34%\"/><col width=\"36%\"/><col width=\"30%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI with Gemcitabine and Cisplatin </content></paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Placebo with Gemcitabine and Cisplatin </content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Laboratory Abnormality</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade</content><footnote ID=\"_Ref184390989\">Graded according to NCI CTCAE version 5.0. Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI with gemcitabine/cisplatin (range: 312 to 335) and Placebo with gemcitabine/cisplatin (range: 319 to 341).</footnote><content styleCode=\"bold\"> 3 or 4 (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade</content><footnoteRef IDREF=\"_Ref184390989\"/><content styleCode=\"bold\"> 3 or 4 (%)</content></paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Chemistry</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hyponatremia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>18</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Gamma-glutamyltransferase increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>12</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased bilirubin</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>14</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypokalemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.4</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased AST</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased ALT</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>7</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Blood creatinine increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.1</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypomagnesemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.2</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypoalbuminemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.9</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hyperkalemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.1</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.1</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased Alkaline Phosphatase</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.8</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypocalcemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.4</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Hematology</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Neutropenia </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>48</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>49</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Anemia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>31</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>28</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Leukopenia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>28</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>28</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Lymphopenia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>23</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>15</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Thrombocytopenia</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>18</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>18</paragraph></td></tr></tbody></table>","<table styleCode=\"Noautorules\" width=\"100.1%\"><caption>Table 17. Adverse Reactions Occurring in &#x2265; 10% of Patients in the HIMALAYA Study</caption><col width=\"37%\"/><col width=\"14%\"/><col width=\"14%\"/><col width=\"18%\"/><col width=\"16%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"/><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI and Tremelimumab-actl</content></paragraph><paragraph><content styleCode=\"bold\">(N = 388)</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Sorafenib</content></paragraph><paragraph><content styleCode=\"bold\">(N = 374)</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">Adverse Reaction</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3-4 (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3-4 (%)</content></paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">Skin and subcutaneous tissue disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Rash<footnote ID=\"_Ref170203834\">Represents a composite of multiple related terms.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>32</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>57</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>12</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pruritus</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>23</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.3</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Gastrointestinal disorders </content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Diarrhea<footnoteRef IDREF=\"_Ref170203834\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>27</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>45</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Abdominal pain<footnoteRef IDREF=\"_Ref170203834\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>20</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>24</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Nausea</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>12</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>14</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">General disorders and administration site conditions</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Fatigue<footnoteRef IDREF=\"_Ref170203834\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>26</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>30</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pyrexia<footnoteRef IDREF=\"_Ref170203834\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>13</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.3</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">Musculoskeletal and Connective Tissue Disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph>Musculoskeletal pain<footnoteRef IDREF=\"_Ref170203834\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>22</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph>Decreased appetite</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>18</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Endocrine disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph>Hypothyroidism<footnoteRef IDREF=\"_Ref170203834\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>14</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">Psychiatric disorders</content></paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Insomnia</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"bottom\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"bottom\"><paragraph>4.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0</paragraph></td></tr></tbody></table>","<table width=\"100.1%\"><caption>Table 18. Laboratory Abnormalities Worsening from Baseline Occurring in &#x2265; 20% of Patients in the HIMALAYA Study</caption><col width=\"31%\"/><col width=\"14%\"/><col width=\"18%\"/><col width=\"18%\"/><col width=\"18%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI and Tremelimumab-actl</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Sorafenib</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Laboratory Abnormality</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Any grade</content><footnote ID=\"_Ref184391526\">Graded according to NCI CTCAE version 4.03.</footnote><content styleCode=\"bold\"> (%)</content><footnote ID=\"_Ref184391574\">Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI with tremelimumab-actl (range: 367-378) and sorafenib (range:344-352).</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3</content><footnoteRef IDREF=\"_Ref184391526\"/><content styleCode=\"bold\"> or 4 (%)</content><footnoteRef IDREF=\"_Ref184391574\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Any grade</content><footnoteRef IDREF=\"_Ref184391526\"/><content styleCode=\"bold\"><sup/>(%)</content><footnoteRef IDREF=\"_Ref184391574\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3</content><footnoteRef IDREF=\"_Ref184391526\"/><content styleCode=\"bold\"> or 4 (%)</content><footnoteRef IDREF=\"_Ref184391574\"/></paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Chemistry</content></paragraph></td><td colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Aspartate Aminotransferase increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>63</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>27</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>55</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>21</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Alanine Aminotransferase increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>56</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>18</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>53</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>12</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Sodium decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>46</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>15</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>40</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Bilirubin increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>41</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>47</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Alkaline Phosphatase increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>41</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>44</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>5</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Glucose increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>39</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>14</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>29</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Calcium decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>34 </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>43</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Albumin decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>31</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>37</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.7</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Potassium increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>28</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>21</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Creatinine increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>21</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>15</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.9</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Hematology</content></paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph>Hemoglobin decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>52</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>40</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph>Lymphocytes decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>41</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>39</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph>Platelets decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>29</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>35</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.1</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><paragraph>Leukocytes decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><paragraph>20</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>30</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>1.1</paragraph></td></tr></tbody></table>","<table width=\"100%\"><caption>Table 19. Adverse Reactions Occurring in &#x2265; 10% of Patients with dMMR tumors in DUO-E</caption><col width=\"48%\"/><col width=\"14%\"/><col width=\"13%\"/><col width=\"11%\"/><col width=\"13%\"/><tbody><tr><td align=\"center\" rowspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Adverse Reactions</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI with Carboplatin and Paclitaxel</content></paragraph><paragraph><content styleCode=\"bold\">(N=44)</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Carboplatin and Paclitaxel </content></paragraph><paragraph><content styleCode=\"bold\">(N=46)</content></paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3-4</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3-4</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Nervous system disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Peripheral neuropathy<footnote ID=\"_Ref184391839\">Includes neuropathy peripheral, peripheral sensory neuropathy, hypoasthesia, peripheral motor neuropathy, and parasthesia.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>61</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>61</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Headache</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>23</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Musculoskeletal and connective tissue disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Musculoskeletal pain<footnote ID=\"_Ref184392182\">Includes arthralgia, pain in extremity, back pain, non-cardiac chest pain, myalgia, musculoskeletal pain, musculoskeletal chest pain, arthritis, bone pain, musculoskeletal stiffness, neck pain, musculoskeletal discomfort, and spinal pain.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>59</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>52</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.2</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Gastrointestinal disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Nausea</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>59</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>48</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.2</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Abdominal pain<footnote ID=\"_Ref184392219\">Includes abdominal pain, abdominal pain lower, flank pain, abdominal discomfort, and abdominal pain upper.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>39</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>24</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.2</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Constipation<footnote ID=\"_Ref184392240\">Includes constipation and fecaloma.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>39</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>35</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.2</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Diarrhea</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>27</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>24</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.2</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Vomiting</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>27</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>22</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.3</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Skin and subcutaneous tissue disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Alopecia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>52</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>41</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Rash<footnote ID=\"_Ref184392267\">Includes eczema, rash, rash erythematous, rash maculo-papular, dermatitis, rash pustular, skin exfoliation, and symmetrical drug-related intertriginous, and flexural exanthema.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>39</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.2</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pruritus</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>16</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">General disorders and administration site conditions</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Fatigue<footnote ID=\"_Ref184392301\">Includes asthenia and fatigue.</footnote></item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>41</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>57</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Peripheral edema<footnote ID=\"_Ref184392340\">Includes peripheral edema, peripheral swelling, and edema.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>16</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.2</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Respiratory, thoracic and mediastinal disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Cough / productive cough</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>27</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>20</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Dyspnea<footnote ID=\"_Ref184392387\">Includes dyspnea and exertional dyspnea.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>25</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased appetite</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>18</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>18</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Infections and infestations</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Upper respiratory tract infection<footnote ID=\"_Ref184392435\">Includes nasopharyngitis, pharyngitis, rhinitis, sinusitis, tracheobronchitis, and upper respiratory tract infection.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>14</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Endocrine disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Hypothyroidism<footnote ID=\"_Ref184392460\">Includes blood thyroid stimulating hormone increased, and hypothyroidism.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>4.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0</paragraph></td></tr></tbody></table>","<table width=\"100%\"><caption>Table 20. Select Laboratory Abnormalities Worsening from Baseline Occurring in &#x2265; 20% of Patients with dMMR tumors in DUO-E</caption><col width=\"35%\"/><col width=\"16%\"/><col width=\"15%\"/><col width=\"15%\"/><col width=\"1%\"/><col width=\"18%\"/><tbody><tr><td rowspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Laboratory Abnormality</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI with Carboplatin and Paclitaxel</content><footnote ID=\"_Ref170206784\">Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI with carboplatin and paclitaxel (range: 40 to 44), and carboplatin and paclitaxel (range: 37 to 46)</footnote></paragraph></td><td align=\"center\" colspan=\"3\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Carboplatin and Paclitaxel</content><footnoteRef IDREF=\"_Ref170206784\"/><content styleCode=\"bold\"/></paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3-4</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3-4</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td></tr><tr><td colspan=\"6\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Chemistry</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Magnesium decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>36</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>30</paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.5</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>ALT increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>32</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>22</paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.2</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>AST increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>30</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>22</paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Potassium decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>25</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>24</paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.2</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Alkaline phosphatase increased</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>20</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>16</paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0</paragraph></td></tr></tbody></table>","<table styleCode=\"Noautorules\" width=\"100%\"><caption>Table 21. Adverse Reactions Occurring in &#x2265; 10% of Patients in the NIAGARA Study</caption><col width=\"23%\"/><col width=\"20%\"/><col width=\"20%\"/><col width=\"19%\"/><col width=\"19%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI with gemcitabine and </content></paragraph><paragraph><content styleCode=\"bold\">cisplatin</content></paragraph><paragraph><content styleCode=\"bold\">N = 530</content></paragraph></td><td colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Gemcitabine and cisplatin </content></paragraph><paragraph><content styleCode=\"bold\">N = 526</content></paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Adverse Reaction</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades</content><footnote ID=\"_Ref194322696\">Graded according to NCI CTCAE version 5.0.</footnote><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade</content><footnoteRef IDREF=\"_Ref194322696\"/><content styleCode=\"bold\"> 3-4 (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades</content><footnoteRef IDREF=\"_Ref194322696\"/><content styleCode=\"bold\"> (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade</content><footnoteRef IDREF=\"_Ref194322696\"/><content styleCode=\"bold\"> 3-4 (%)</content></paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Gastrointestinal disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Nausea</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>54</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>48</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Constipation</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>39</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>39</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Diarrhea</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>21</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>14</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.4</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Vomiting<footnote ID=\"_Ref194322861\">Includes multiple similar terms.</footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>20</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>19</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.2</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Abdominal pain<footnoteRef IDREF=\"_Ref194322861\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>20</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">General disorders and administration site conditions</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Fatigue<footnoteRef IDREF=\"_Ref194322861\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>52</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>49</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pyrexia<footnoteRef IDREF=\"_Ref194322861\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>22</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Edema<footnoteRef IDREF=\"_Ref194322861\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased appetite</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>27</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>25</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.6</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Skin and subcutaneous tissue disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Rash<footnoteRef IDREF=\"_Ref194322861\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>23</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>12</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pruritus</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>15</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>7</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Nervous system disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Peripheral neuropathy<footnoteRef IDREF=\"_Ref194322861\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>16</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>14</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Headache<footnoteRef IDREF=\"_Ref194322861\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Dizziness<footnoteRef IDREF=\"_Ref194322861\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.2</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Endocrine disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypothyroidism<footnoteRef IDREF=\"_Ref194322861\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Vascular disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypertension<footnoteRef IDREF=\"_Ref194322861\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>12</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.9</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Hemorrhage<footnoteRef IDREF=\"_Ref194322861\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0.9</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>2.1</paragraph></td></tr></tbody></table>","<table styleCode=\"Noautorules\" width=\"539.75pt\"><caption>Table 22. Select Laboratory Abnormalities That Worsened from Baseline in &#x2265; 20% of Patients Who Received IMFINZI with Chemotherapy in the NIAGARA study</caption><col width=\"39%\"/><col width=\"15%\"/><col width=\"15%\"/><col width=\"15%\"/><col width=\"15%\"/><tbody><tr><td rowspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Laboratory Abnormality</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI with gemcitabine and cisplatin</content><footnote ID=\"_Ref194323407\">Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI plus chemotherapy (range: 482 to 528), and chemotherapy (range: 467 to 521).</footnote></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Gemcitabine and cisplatin</content><footnoteRef IDREF=\"_Ref194323407\"/></paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>All Grades<footnote ID=\"_Ref194323568\">Graded per NCI CTCAE V5.</footnote></paragraph><paragraph>(%)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>Grade<footnoteRef IDREF=\"_Ref194323568\"/></paragraph><paragraph>3 or 4</paragraph><paragraph>(%)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>All</paragraph><paragraph>Grades<footnoteRef IDREF=\"_Ref194323568\"/></paragraph><paragraph>(%)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>Grade<footnoteRef IDREF=\"_Ref194323568\"/></paragraph><paragraph>3 or 4</paragraph><paragraph>(%)</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Chemistry</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased blood creatinine </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>63</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>58</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>7</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased sodium </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>54</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>55</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased ALT </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>53</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>54</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased calcium </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>52</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>43</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.2</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased potassium </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>51</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>49</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.4</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased AST</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>42</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>39</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.1</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased magnesium</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>38</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.9</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>37</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased alkaline phosphate</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>26</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>25</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.4</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Hematology</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased hemoglobin</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>88</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>87</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased neutrophils</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>76</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>31</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>74</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>34</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased platelets</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>52</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>50</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>7</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Decreased lymphocytes</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>44</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>40</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>8</paragraph></td></tr></tbody></table>","<table styleCode=\"Noautorules\" width=\"539.75pt\"><caption>Table 23: Adverse Reactions Occurring in &#x2265; 10% of Patients in the MATTERHORN study</caption><col width=\"27%\"/><col width=\"18%\"/><col width=\"18%\"/><col width=\"18%\"/><col width=\"18%\"/><tbody><tr><td rowspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Adverse Reaction</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI with FLOT Chemotherapy</content></paragraph><paragraph><content styleCode=\"bold\">N=475</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Placebo with FLOT Chemotherapy</content></paragraph><paragraph><content styleCode=\"bold\">N=469</content></paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3 or 4 (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades (%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade 3 or 4 (%)</content></paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Gastrointestinal disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Diarrhea<footnote ID=\"_Ref215055924\">Includes multiple similar terms. </footnote></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>64</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>59</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>7</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Nausea</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>51</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>51</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Vomiting<footnoteRef IDREF=\"_Ref215055924\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>26</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.1</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>26</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Abdominal pain<footnoteRef IDREF=\"_Ref215055924\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>27</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>29</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Stomatitis<footnoteRef IDREF=\"_Ref215055924\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>20</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.1</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>15</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Constipation</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>16</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.9</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Dysphagia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Nervous system disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Peripheral neuropathy<footnoteRef IDREF=\"_Ref215055924\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>51</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>47</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.3</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Dysgeusia<footnoteRef IDREF=\"_Ref215055924\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>19</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>15</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">General disorders and administration site conditions</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Fatigue<footnoteRef IDREF=\"_Ref215055924\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>47</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>45</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>5</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pyrexia<footnoteRef IDREF=\"_Ref215055924\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>20</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>16</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.3</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Skin and subcutaneous tissue disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Alopecia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>31</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>32</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Rash<footnoteRef IDREF=\"_Ref215055924\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>30</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>20</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.4</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pruritus<footnoteRef IDREF=\"_Ref215055924\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased appetite<footnoteRef IDREF=\"_Ref215055924\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>31</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>30</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.1</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Musculoskeletal and connective tissue disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Musculoskeletal pain<footnoteRef IDREF=\"_Ref215055924\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>21</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>19</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.6</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Infections and infestations</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>COVID-19<footnoteRef IDREF=\"_Ref215055924\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>19</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.7</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>16</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pneumonia<footnoteRef IDREF=\"_Ref215055924\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>11</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.3</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Investigations</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Weight decreased</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>15</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.1</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>19</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.4</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Vascular disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hemorrhage<footnoteRef IDREF=\"_Ref215055924\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>14</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>15</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.8</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Respiratory, thoracic and mediastinal disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Cough<footnoteRef IDREF=\"_Ref215055924\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0</paragraph></td></tr></tbody></table>","<table styleCode=\"Noautorules\" width=\"539.75pt\"><caption>Table 24: Laboratory Abnormalities (&gt; 20%) That Worsened from Baseline in Patients with Disease Who Received IMFINZI with FLOT Chemotherapy in MATTERHORN</caption><col width=\"39%\"/><col width=\"15%\"/><col width=\"15%\"/><col width=\"15%\"/><col width=\"15%\"/><tbody><tr><td rowspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Laboratory Abnormality</content><footnote ID=\"_Ref215056712\">Graded per NCI CTCAE v5.0</footnote></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI with FLOT Chemotherapy</content><footnote ID=\"_Ref215056827\">The denominator used to calculate the rate varied from 444 to 472 based on the number of patients with a baseline value and at least one post-treatment value. </footnote></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Placebo with FLOT Chemotherapy</content><footnote ID=\"_Ref215056839\">The denominator used to calculate the rate varied from 443 to 468 based on the number of patients with a baseline value and at least one post-treatment value. </footnote></paragraph></td></tr><tr><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All Grades</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade </content></paragraph><paragraph><content styleCode=\"bold\">3 or 4</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">All</content></paragraph><paragraph><content styleCode=\"bold\">Grades</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Grade </content></paragraph><paragraph><content styleCode=\"bold\">3 or 4</content></paragraph><paragraph><content styleCode=\"bold\">(%)</content></paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Hematology</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased leukocytes </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>75</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>14</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>79</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>17</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased neutrophils</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>70</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>41</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>74</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>44</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased hemoglobin</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>68</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>7</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>73</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased lymphocytes</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>49</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>45</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>13</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased platelets</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>47</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.1</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>46</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.9</paragraph></td></tr><tr><td colspan=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Chemistry</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased AST</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>72</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>69</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased ALT</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>70</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>7</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>65</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased GGT</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>57</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>10</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>51</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased lipase</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>55</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>16</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>55</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>15</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased alkaline phosphatase</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>53</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.2</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>51</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased calcium </paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>45</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>47</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.6</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Increased amylase</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>42</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>6</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>39</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.5</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased potassium</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>39</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>40</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>8</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased sodium</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>33</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.4</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>32</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.7</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Decreased albumin</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>31</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.5</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>31</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>0.2</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Increased potassium</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>22</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0.6</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>26</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>1.3</paragraph></td></tr></tbody></table>","<table width=\"100%\"><caption>Table 25: Safety Profile by Phase of Treatment</caption><col width=\"39%\"/><col width=\"31%\"/><col width=\"31%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMFINZI with FLOT Chemotherapy</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Placebo with FLOT Chemotherapy</content></paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Neoadjuvant Phase </content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph> Number of Patients</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>475</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>469</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph> Serious Adverse Reactions</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>21%</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>18%</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph> Deaths during Treatment-emergent period</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.9%</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.7%</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption> Permanent discontinuation of IMFINZI or Placebo</item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.5%</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.1%</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph> No surgery due to Adverse Reaction</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>0.6%</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>0.4%</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph> Delay in surgery due to Adverse Reaction</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>2.3%</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>2.6%</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Adjuvant Phase </content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph> Number of Patients</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>365</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>351</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph> Serious Adverse Reactions</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>29%</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>26%</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph> Deaths during Treatment-emergent period</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.2%</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.6%</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption> Permanent discontinuation of IMFINZI or Placebo</item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>7%</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>4.6%</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Adjuvant Phase (IMFINZI as a single-agent)</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph> Number of Patients</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>345</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>331</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph> Serious Adverse Reactions</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>14%</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>15%</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph> Deaths during Treatment-emergent period</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1.7%</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>2.4%</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption> Permanent discontinuation of IMFINZI or Placebo</item></list></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>6%</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>2.7%</paragraph></td></tr></tbody></table>"],"information_for_patients":["17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Immune-Mediated Adverse Reactions Inform patients of the risk of immune-mediated adverse reactions that may require corticosteroid treatment and interruption or discontinuation of IMFINZI [see Warnings and Precautions (5.1) ] , including: • Pneumonitis: Advise patients to contact their healthcare provider immediately for any new or worsening cough, chest pain, or shortness of breath. • Hepatitis: Advise patients to contact their healthcare provider immediately for jaundice, severe nausea or vomiting, pain on the right side of abdomen, lethargy, or easy bruising or bleeding. • Colitis: Advise patients to contact their healthcare provider immediately for diarrhea, blood or mucus in stools, or severe abdominal pain. • Endocrinopathies: Advise patients to contact their healthcare provider immediately for signs or symptoms of hypothyroidism, hyperthyroidism, adrenal insufficiency, type 1 diabetes mellitus, or hypophysitis. • Nephritis: Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis. • Dermatological Reactions: Advise patients to contact their healthcare provider immediately for signs or symptoms of severe dermatological reactions. • Pancreatitis: Advise patients to contact their healthcare provider immediately for signs or symptoms of pancreatitis. • Other Immune-Mediated Adverse Reactions: Advise patients to contact their healthcare provider immediately for signs or symptoms of pancreatitis, aseptic meningitis, encephalitis, immune thrombocytopenia, myocarditis, hemolytic anemia, myositis, uveitis, keratitis, and myasthenia gravis. Infusion-Related Reactions : • Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions [see Warnings and Precautions (5.2) ] . Complications of Allogeneic HSCT : • Advise patients of potential risk of post-transplant complications [see Warnings and Precautions (5.3) ] . Embryo-Fetal Toxicity: • Advise females of reproductive potential that IMFINZI can cause harm to a fetus and to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1, 8.3 )] . • Advise females of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of IMFINZI [see Use in Specific Populations (8.3) ] . Lactation : • Advise female patients not to breastfeed while taking IMFINZI and for 3 months after the last dose [see Warnings and Precautions (5.4) and Use in Specific Populations (8.2) ] . Manufactured for: AstraZeneca Pharmaceuticals LP Wilmington, DE 19850"],"spl_unclassified_section":["MEDICATION GUIDE MEDICATION GUIDE IMFINZI ® (im-FIN-zee) (durvalumab) injection What is the most important information I should know about IMFINZI? IMFINZI is a medicine that may treat certain cancers by working with your immune system. IMFINZI can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended. Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including: • Lung problems . ∘ cough ∘ shortness of breath ∘ chest pain • Intestinal problems. ∘ diarrhea (loose stools) or more frequent bowel movements than usual ∘ stools that are black, tarry, sticky, or have blood or mucus ∘ severe stomach-area (abdomen) pain or tenderness • Liver problems. ∘ yellowing of your skin or the whites of your eyes ∘ severe nausea or vomiting ∘ pain on the right side of your stomach-area (abdomen) ∘ dark urine (tea colored) ∘ bleeding or bruising more easily than normal • Hormone and gland problems. ∘ headaches that will not go away or unusual headaches ∘ eye sensitivity to light ∘ eye problems ∘ rapid heartbeat ∘ increase sweating ∘ extreme tiredness ∘ weight gain or weight loss ∘ feeling more hungry or thirsty than usual ∘ urinating more often than usual ∘ hair loss ∘ feeling cold ∘ constipation ∘ your voice gets deeper ∘ dizziness or fainting ∘ changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness • Kidney problems. ∘ decrease in your amount of urine ∘ blood in your urine ∘ swelling of your ankles ∘ loss of appetite • Skin problems. ∘ rash ∘ itching ∘ skin blistering or peeling ∘ painful sores or ulcers in mouth or nose, throat, or genital area ∘ fever or flu-like symptoms ∘ swollen lymph nodes • Pancreas problems. ∘ pain in your upper stomach area (abdomen) ∘ severe nausea or vomiting ∘ loss of appetite • Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with IMFINZI. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include: ∘ chest pain, irregular heartbeats, shortness of breath or swelling of ankles ∘ confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems ∘ tingling, numbness or weakness of the arms or legs ∘ double vision, blurry vision, sensitivity to light, eye pain, changes in eye-sight ∘ persistent or severe muscle pain or weakness, muscle cramps, joint pain, joint stiffness or swelling ∘ low red blood cells, bruising • Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include: ∘ chills or shaking ∘ itching or rash ∘ flushing ∘ shortness of breath or wheezing ∘ dizziness ∘ feel like passing out ∘ fever ∘ back or neck pain • Rejection of a transplanted organ or tissue. Your healthcare provider should tell you what signs and symptoms you should report and monitor you depending on the type of organ or tissue transplant that you have had. • Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with IMFINZI. Your healthcare provider will monitor you for these complications. Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with IMFINZI. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with IMFINZI, if you have severe side effects. What is IMFINZI? IMFINZI is a prescription medicine used to treat adults with: • a type of lung cancer called non-small cell lung cancer (NSCLC). ∘ IMFINZI may be used in combination with chemotherapy that contains platinum prior to surgery and alone after surgery when your NSCLC: ▪ can be removed by surgery, and ▪ is not known to have an abnormal “EGFR” or “ALK” gene. ∘ IMFINZI may be used alone when your NSCLC: ▪ has not spread outside your chest ▪ cannot be removed by surgery, and ▪ has responded or stabilized with initial treatment with chemotherapy that contains platinum, given at the same time as radiation therapy. ∘ IMFINZI may be used in combination with tremelimumab-actl and chemotherapy that contains platinum when your NSCLC: ▪ has spread to other parts of your body (metastatic), and ▪ does not have an abnormal “EGFR” or “ALK” gene. • a type of lung cancer called small cell lung cancer (SCLC). ∘ for limited-stage small cell lung cancer (LS-SCLC), IMFINZI may be used alone when your LS-SCLC cannot be removed by surgery, and ∘ has responded or stabilized after initial treatment with chemotherapy that contains platinum, given at the same time as radiation therapy. ∘ for extensive-stage small cell lung cancer (ES-SCLC), IMFINZI may be used with the chemotherapy medicines etoposide and either carboplatin or cisplatin as your first treatment when your ES-SCLC has spread within your lungs or to other parts of the body. • a type of cancer called biliary tract cancer (BTC), including cancer of the bile ducts (cholangiocarcinoma) and gallbladder cancer. IMFINZI may be used in combination with chemotherapy medicines gemcitabine and cisplatin when your BTC: ∘ has spread to nearby tissues (locally advanced), or ∘ has spread to other parts of the body (metastatic). • a type of liver cancer that cannot be removed by surgery (unresectable hepatocellular carcinoma or uHCC ). IMFINZI is used in combination with tremelimumab-actl to treat uHCC. • a type of uterine cancer called endometrial cancer . IMFINZI may be used in combination with chemotherapy medicines carboplatin and paclitaxel followed by IMFINZI alone when your endometrial cancer: ∘ has spread (advanced) or has come back (recurrent), and ∘ a laboratory test shows that your tumor is mismatch repair deficient (dMMR). • a type of bladder cancer called muscle invasive bladder cancer (MIBC) that has spread into the muscle layer of the bladder but not to other parts of the body. IMFINZI may be used in combination with gemcitabine and cisplatin (neoadjuvant treatment) prior to the surgical removal of your bladder followed by IMFINZI alone after surgery (adjuvant treatment). • A type of stomach cancer called gastric cancer (GC) or gastro-esophageal junction adenocarcinoma (GEJC) that can be removed by surgery. IMFINZI is used in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) prior to and after surgery followed by IMFINZI alone. It is not known if IMFINZI is safe and effective in children. Before you receive IMFINZI, tell your healthcare provider about all of your medical conditions, including if you: • have immune system problems such as Crohn's disease, ulcerative colitis, or lupus • have received an organ or tissue transplant, including corneal transplant • have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic) • have received radiation treatment to your chest area • have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome • are pregnant or plan to become pregnant. IMFINZI can harm your unborn baby Females who are able to become pregnant: ∘ Your healthcare provider will give you a pregnancy test before you start treatment with IMFINZI. ∘ You should use an effective method of birth control during your treatment and for 3 months after the last dose of IMFINZI. Talk to your healthcare provider about birth control methods that you can use during this time. ∘ Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with IMFINZI. • are breastfeeding or plan to breastfeed. It is not known if IMFINZI passes into your breast milk. Do not breastfeed during treatment and for 3 months after the last dose of IMFINZI. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. How will I receive IMFINZI? • Your healthcare provider will give you IMFINZI into your vein through an intravenous (IV) line over 60 minutes. • IMFINZI is usually given every 2, 3 or 4 weeks. • Your healthcare provider will decide how many treatments you need. • Your healthcare provider will test your blood to check you for certain side effects. • If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. What are the possible side effects of IMFINZI? IMFINZI can cause serious side effects, including: See “What is the most important information I should know about IMFINZI?” The most common side effects of IMFINZI when used with platinum-containing chemotherapy in adults with NSCLC that can be removed by surgery include: • low red blood cells (anemia) • nausea • constipation • feeling tired • muscle or bone pain • rash The most common side effects of IMFINZI when used alone in adults with NSCLC that cannot be removed by surgery include: • cough • feeling tired • inflammation in the lungs • upper respiratory tract infections • shortness of breath • rash The most common side effects of IMFINZI when used with tremelimumab-actl and platinum-containing chemotherapy in adults with metastatic NSCLC include: • nausea • feeling tired or weak • muscle or bone pain • decreased appetite • rash • diarrhea The most common side effects of IMFINZI when used alone in adults with LS-SCLC include: • inflammation in the lungs • feeling tired or weak The most common side effects of IMFINZI when used with etoposide and either carboplatin or cisplatin in adults with ES-SCLC include: • nausea • hair loss • feeling tired or weak The most common side effects of IMFINZI when used with gemcitabine and cisplatin in adults with BTC include: • feeling tired • nausea • constipation • decreased appetite • stomach (abdominal) pain • rash • fever The most common side effects of IMFINZI when used with tremelimumab-actl in adults with uHCC include: • rash • diarrhea • feeling tired • itchiness • muscle or bone pain • stomach (abdominal) pain The most common side effects of IMFINZI when used with carboplatin and paclitaxel in adults with endometrial cancer include: • inflammation of the nerves causing numbness, weakness, tingling or burning pain of the arms and legs • muscle or bone pain • nausea • hair loss • feeling tired • stomach (abdominal) pain • constipation • rash • decreased level of magnesium in the blood • increased liver function tests • diarrhea • vomiting • cough • decreased level of potassium in the blood • shortness of breath • headache • increased level of alkaline phosphatase in the blood The most common side effects of IMFINZI when used with gemcitabine and cisplatin in adults with MIBC include: • decreased red blood cells (anemia) • decreased white blood cells • increased level of creatinine in the blood • decreased level of sodium in the blood • nausea • increased liver function tests • decreased level of calcium in the blood • decreased blood platelet counts • feeling tired • increased level of potassium in the blood • decreased lymphocyte counts • constipation • decreased level of magnesium in the blood • decreased appetite • increased level of alkaline phosphatase in the blood • rash • fever • diarrhea • vomiting • stomach (abdominal) pain The most common side effects of IMFINZI when used with FLOT in adults with GC or GEJC include: Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of IMFINZI. Ask your healthcare provider or pharmacist for more information. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. General information about the safe and effective use of IMFINZI. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. If you would like more information about IMFINZI, talk with your healthcare provider. You can ask your healthcare provider for information about IMFINZI that is written for health professionals. What are the ingredients in IMFINZI? Active ingredient: durvalumab Inactive ingredients: L-histidine, L-histidine hydrochloride monohydrate, α,α-trehalose dihydrate, polysorbate 80, Water for Injection, USP. Manufactured for: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850 By: AstraZeneca UK Limited, 1 Francis Crick Ave. Cambridge, England CB2 0AA US License No. 2043 IMFINZI is a registered trademark of AstraZeneca group of companies. For more information, call 1-800-236-9933 or go to www.IMFINZI.com © AstraZeneca 2025 This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 11/2025"],"dosage_and_administration":["2 DOSAGE AND ADMINISTRATION • Administer IMFINZI as an intravenous infusion over 60 minutes after dilution. ( 2.4 ) • Neoadjuvant and Adjuvant Treatment of Resectable NSCLC: ∘ Weight ≥ 30 kg: Neoadjuvant : IMFINZI 1,500 mg in combination with chemotherapy every 3 weeks for up to 4 cycles prior to surgery. Adjuvant : IMFINZI 1,500 mg as a single agent every 4 weeks for up to 12 cycles after surgery. ( 2.2 ) ∘ Weight < 30 kg Neoadjuvant : IMFINZI 20 mg/kg every 3 weeks in combination with chemotherapy for up to 4 cycles prior to surgery. Adjuvant : 20 mg/kg every 4 weeks as a single agent for up to 12 cycles after surgery. ( 2.2 ) • Unresectable Stage III NSCLC, following concurrent platinum-based chemotherapy and radiation therapy: ∘ Weight ≥ 30 kg: IMFINZI 10 mg/kg every 2 weeks or 1,500 mg every 4 weeks. ( 2.2 ) ∘ Weight < 30 kg: IMFINZI 10 mg/kg every 2 weeks. ( 2.2 ) • Metastatic NSCLC: ∘ Weight ≥ 30 kg: IMFINZI 1,500 mg every 3 weeks in combination with tremelimumab-actl 75 mg and platinum-based chemotherapy for 4 cycles, and then administer IMFINZI 1,500 mg every 4 weeks as a single agent with histology-based pemetrexed maintenance therapy every 4 weeks, and a fifth dose of tremelimumab-actl 75 mg in combination with IMFINZI dose 6 at week 16. ( 2.2 ) ∘ Weight < 30 kg: IMFINZI 20 mg/kg every 3 weeks in combination with tremelimumab-actl 1 mg/kg and platinum-based chemotherapy, and then administer IMFINZI 20 mg/kg every 4 weeks as a single agent with histology-based pemetrexed therapy every 4 weeks, and a fifth dose of tremelimumab-actl 1 mg/kg in combination with IMFINZI dose 6 at week 16. ( 2.2 ) • LS-SCLC, following concurrent platinum-based chemotherapy and radiation therapy: ∘ Weight ≥ 30 kg: 1,500 mg every 4 weeks. ( 2.2 ) ∘ Weight < 30 kg: 20 mg/kg every 4 weeks. ( 2.2 ) • ES-SCLC: ∘ Weight ≥ 30 kg: With etoposide and either carboplatin or cisplatin, administer IMFINZI 1,500 mg every 3 weeks in combination with chemotherapy, and then 1,500 mg every 4 weeks as a single agent. ( 2.2 ) ∘ Weight < 30 kg: With etoposide and either carboplatin or cisplatin, administer IMFINZI 20 mg/kg every 3 weeks in combination with chemotherapy, and then 10 mg/kg every 2 weeks as a single agent. ( 2.2 ) • BTC: ∘ Weight ≥ 30 kg: administer IMFINZI 1,500 mg every 3 weeks in combination with chemotherapy, and then 1,500 mg every 4 weeks as a single agent. ( 2.2 ) ∘ Weight < 30 kg: administer IMFINZI 20 mg/kg every 3 weeks in combination with chemotherapy, and then 20 mg/kg every 4 weeks as a single agent. ( 2.2 ) • uHCC: ∘ Weight ≥ 30 kg: IMFINZI 1,500 mg in combination with tremelimumab-actl 300 mg as a single dose at Cycle 1/Day 1, followed by IMFINZI as a single agent every 4 weeks. ( 2.2 ) ∘ Weight < 30 kg: IMFINZI 20 mg/kg in combination with tremelimumab-actl 4 mg/kg as a single dose at Cycle 1/Day 1, followed by IMFINZI as a single agent every 4 weeks. ( 2.2 ) • dMMR endometrial cancer: ∘ Weight ≥ 30 kg: IMFINZI 1,120 mg in combination with carboplatin and paclitaxel every 3 weeks for 6 cycles, followed by IMFINZI 1,500 mg every 4 weeks as a single agent. ( 2.1 , 2.2 ) ∘ Weight < 30 kg: IMFINZI 15 mg/kg in combination with carboplatin and paclitaxel every 3 weeks for 6 cycles, followed by IMFINZI 20 mg/kg every 4 weeks as a single agent. ( 2.1 , 2.2 ) • MIBC: ∘ Weight ≥ 30 kg: Neoadjuvant: IMFINZI 1,500 mg in combination with gemcitabine and cisplatin every 3 weeks for 4 cycles prior to surgery. Adjuvant: IMFINZI 1,500 mg every 4 weeks as a single agent for up to 8 cycles after surgery. ( 2.2 ) ∘ Weight < 30 kg: Neoadjuvant: IMFINZI 20 mg/kg in combination with gemcitabine and cisplatin every 3 weeks for 4 cycles prior to surgery. Adjuvant: IMFINZI 20 mg/kg every 4 weeks as a single agent for up to 8 cycles after surgery. ( 2.2 ) • See full Prescribing Information for preparation and administration instructions and dosage modifications for adverse reactions. 2.1 Patient Selection Advanced or Recurrent dMMR Endometrial Cancer Select patients for treatment based on the presence of dMMR in tumor specimens [see Clinical Studies (14.5) ]. Information on FDA-approved tests for the detection of dMMR status in endometrial cancer is available at https://www.fda.gov/companiondiagnostics . 2.2 Recommended Dosage The recommended dosages for IMFINZI as a single agent and IMFINZI in combination with other therapeutic agents are presented in Table 1. The recommended dosage schedule and regimens for IMFINZI for the treatment of metastatic NSCLC are provided in Tables 2 and 3 [see Indications and Usage (1.1) ]. Administer IMFINZI as a 60 minute intravenous infusion after dilution [ see Dosage and Administration (2.3) ]. Table 1. Recommended Dosages of IMFINZI Indication Recommended IMFINZI Dosage Duration of Therapy Neoadjuvant and Adjuvant Treatment of Resectable NSCLC Patients with a body weight of ≥ 30 kg: Neoadjuvant: IMFINZI 1,500 mg in combination with chemotherapy Administer IMFINZI prior to chemotherapy on the same day. Refer to the Prescribing Information for the agent administered in combination with IMFINZI for recommended dosage information, as appropriate. every 3 weeks for up to 4 cycles prior to surgery Adjuvant: IMFINZI 1,500 mg as a single agent every 4 weeks for up to 12 cycles after surgery. Patients with a body weight of < 30 kg: Neoadjuvant: IMFINZI 20 mg/kg every 3 weeks in combination with chemotherapy for up to 4 cycles prior to surgery. Adjuvant: IMFINZI 20 mg/kg every 4 weeks for up to 12 cycles as a single agent after surgery. Until disease progression that precludes definitive surgery, recurrence, unacceptable toxicity, or a maximum of 12 cycles after surgery Unresectable Stage III NSCLC Following concurrent platinum-based chemotherapy and radiation therapy: Patients with a body weight of ≥ 30 kg: 10 mg/kg every 2 weeks or 1,500 mg every 4 weeks Patients with a body weight of < 30 kg: 10 mg/kg every 2 weeks Until disease progression, unacceptable toxicity, or a maximum of 12 months Limited Stage SCLC Following concurrent platinum-based chemotherapy and radiation therapy: Patients with a body weight of ≥ 30 kg: 1,500 mg every 4 weeks Patients with a body weight of < 30 kg: 20 mg/kg every 4 weeks Until disease progression, unacceptable toxicity, or a maximum of 24 months Extensive Stage SCLC Patients with a body weight of ≥ 30 kg: 1,500 mg in combination with chemotherapy every 3 weeks (21 days) for 4 cycles, followed by 1,500 mg every 4 weeks as a single agent Patients with a body weight of < 30 kg: 20 mg/kg in combination with chemotherapy every 3 weeks (21 days) for 4 cycles, followed by 10 mg/kg every 2 weeks as a single agent Until disease progression or until unacceptable toxicity BTC Patients with a body weight of ≥ 30 kg: 1,500 mg in combination with chemotherapy every 3 weeks (21 days) up to 8 cycles followed by 1,500 mg every 4 weeks as a single agent Patients with a body weight of < 30 kg: 20 mg/kg in combination with chemotherapy every 3 weeks (21 days) up to 8 cycles, followed by 20 mg/kg every 4 weeks as a single agent Until disease progression or until unacceptable toxicity uHCC Patients with a body weight of ≥ 30 kg: IMFINZI 1,500 mg following a single dose of tremelimumab-actl Administer tremelimumab-actl prior to IMFINZI on the same day. When tremelimumab-actl is administered in combination with IMFINZI, refer to the Prescribing Information for tremelimumab-actl dosing information. 300 mg at Day 1 of Cycle 1; Continue IMFINZI 1,500 mg as a single agent every 4 weeks Patients with a body weight of < 30 kg: IMFINZI 20 mg/kg following a single dose of tremelimumab-actl 4 mg/kg at Day 1 of Cycle 1; Continue IMFINZI 20 mg/kg as a single agent every 4 weeks After Cycle 1 of combination therapy, administer IMFINZI as a single agent every 4 weeks until disease progression or unacceptable toxicity dMMR endometrial cancer Patients with a body weight of ≥ 30 kg: IMFINZI 1,120 mg in combination with carboplatin and paclitaxel every 3 weeks (21 days) for 6 cycles, followed by IMFINZI 1,500 mg every 4 weeks as a single agent Patients with a body weight of < 30 kg: IMFINZI 15 mg/kg in combination with carboplatin and paclitaxel every 3 weeks (21 days) for 6 cycles, followed by IMFINZI 20 mg/kg every 4 weeks as a single agent Until disease progression or unacceptable toxicity Neoadjuvant and Adjuvant Treatment of MIBC Patients with a body weight of ≥30 kg: Neoadjuvant: 1,500 mg in combination with gemcitabine and cisplatin every 3 weeks for 4 cycles prior to surgery Adjuvant: IMFINZI 1,500 mg as a single agent every 4 weeks for up to 8 cycles after surgery Patients with a body weight of < 30 kg: Neoadjuvant: 20 mg/kg in combination with gemcitabine and cisplatin every 3 weeks for 4 cycles prior to surgery Adjuvant: IMFINZI 20 mg/kg as a single agent every 4 weeks for up to 8 cycles after surgery Until disease progression that precludes definitive surgery, recurrence, or unacceptable toxicity or a maximum of 8 cycles after surgery Neoadjuvant and Adjuvant Treatment of Resectable GC/GEJC Patients with a body weight of ≥ 30 kg: Neoadjuvant: IMFINZI 1,500 mg every 4 weeks with FLOT FLOT chemotherapy is administered on days 1 and 15 of each 4 week cycle [See Clinical Studies ( 14.7 )] . for up to 2 cycles prior to surgery Adjuvant: IMFINZI 1,500 mg every 4 weeks with FLOT for up to 2 cycles, followed by IMFINZI 1,500 mg as a single agent every 4 weeks for up to 10 cycles Patients with a body weight of < 30 kg: Neoadjuvant: IMFINZI 20 mg/kg every 4 weeks with FLOT*± for up to 2 cycles prior to surgery Adjuvant: IMFINZI 20 mg/kg every 4 weeks with FLOT for up to 2 cycles, followed by IMFINZI 20 mg/kg as a single agent every 4 weeks for up to 10 cycles Neoadjuvant: Until disease progression that precludes definitive surgery or unacceptable toxicity IMFINZI in Combination with Tremelimumab-actl and Platinum-Based Chemotherapy The recommended dosage schedule and regimens for IMFINZI for the treatment of metastatic NSCLC are provided in Tables 2 and 3. Weigh patients prior to each infusion. Calculate the appropriate dose using Table 3 below based on the patient’s weight and tumor histology. Table 2. Recommended Dosage Schedule for Metastatic NSCLC Week continue IMFINZI until disease progression or intolerable toxicity. note the dosing interval change from every 3 weeks to every 4 weeks starting at cycle 5. 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Cycle: 1 2 3 4 5 6 7 8 IMFINZI intravenous infusion over 60 minutes [see Dosage and Administration (2.4) ] . X X X X X X X X Tremelimumab-actl if patients receive fewer than 4 cycles of platinum-based chemotherapy, the remaining cycles of tremelimumab-actl (up to a total of 5) should be given after the platinum-based chemotherapy phase, in combination with IMFINZI, every 4 weeks. X X X X X Chemotherapy X X X X X optional pemetrexed therapy from week 12 until disease progression or intolerable toxicity for patients with non-squamous disease who received treatment with pemetrexed and carboplatin/cisplatin. X X X Table 3. Recommended Regimen and Dosage for Metastatic NSCLC Tumor Histology Patient Weight IMFINZI Dosage Tremelimumab-actl Dosage Refer to the Prescribing Information for dosing information. Platinum-based Chemotherapy Regimen Non-Squamous ≥ 30 kg 1,500 mg 75 mg • carboplatin & nab-paclitaxel OR • carboplatin or cisplatin & pemetrexed < 30 kg 20 mg/kg 1 mg/kg Squamous ≥ 30 kg 1,500 mg 75 mg • carboplatin & nab-paclitaxel OR • carboplatin or cisplatin & gemcitabine < 30 kg 20 mg/kg 1 mg/kg 2.3 Dosage Modifications for Adverse Reactions No dose reduction for IMFINZI is recommended. In general, withhold IMFINZI for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue IMFINZI for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating corticosteroids. Dosage modifications for IMFINZI or IMFINZI in combination with tremelimumab-actl or chemotherapy for adverse reactions that require management different from these general guidelines are summarized in Table 4. Table 4. Recommended Dosage Modifications for Adverse Reactions Adverse Reaction Severity Based on National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. Dosage Modification Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1) ] Pneumonitis Grade 2 Withhold Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids or an inability to reduce corticosteroid dose to 10 mg of prednisone or less per day (or equivalent) within 12 weeks of initiating corticosteroids. Grade 3 or 4 Permanently discontinue Colitis Grade 2 Withhold Grade 3 Withhold or permanently discontinue Permanently discontinue IMFINZI for Grade 3 colitis when administered as part of a tremelimumab-actl containing regimen. Grade 4 Permanently discontinue Intestinal perforation Any grade Permanently discontinue Hepatitis with no tumor involvement of the liver ALT or AST increases to more than 3 and up to 8 times the ULN or total bilirubin increases to more than 1.5 and up to 3 times ULN Withhold ALT or AST increases to more than 8 times ULN or total bilirubin increases to more than 3 times the ULN Permanently discontinue Hepatitis with tumor involvement of the liver If AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue IMFINZI based on recommendations for hepatitis with no liver involvement. AST or ALT is more than 1 and up to 3 times ULN at baseline and increases to more than 5 and up to 10 times ULN or AST or ALT is more than 3 and up to 5 times ULN at baseline and increases to more than 8 and up to 10 times ULN Withhold AST or ALT increases to more than 10 times ULN or total bilirubin increases to more than 3 times ULN Permanently discontinue Endocrinopathies Grade 3 or 4 Withhold until clinically stable or permanently discontinue depending on severity Nephritis with Renal Dysfunction Grade 2 or 3 increased blood creatinine Withhold Grade 4 increased blood creatinine Permanently discontinue Exfoliative Dermatologic Conditions Suspected SJS, TEN, or DRESS Withhold Confirmed SJS, TEN, or DRESS Permanently discontinue Myocarditis Grade 2, 3, or 4 Permanently discontinue Neurological Toxicities Grade 2 Withhold Grade 3 or 4 Permanently discontinue Other Adverse Reactions Infusion-related reactions [see Warnings and Precautions (5.2) ] Grade 1 or 2 Interrupt or slow the rate of infusion Grade 3 or 4 Permanently discontinue ALT = alanine aminotransferase, AST = aspartate aminotransferase, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson Syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit normal. 2.4 Preparation and Administration Preparation • Visually inspect drug product for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard the vial if the solution is cloudy, discolored, or visible particles are observed. • Do not shake the vial. • Withdraw the required volume from the vial(s) of IMFINZI and transfer into an intravenous bag containing 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Mix diluted solution by gentle inversion. Do not shake the solution. The final concentration of the diluted solution should be between 1 mg/mL and 15 mg/mL. • Discard partially used or empty vials of IMFINZI. Storage of Infusion Solution • IMFINZI does not contain a preservative. • Administer infusion solution immediately once prepared. If the infusion solution is not administered immediately and needs to be stored, the time from preparation until the completion of the infusion should not exceed: ∘ 28 days in a refrigerator at 2°C to 8°C (36°F to 46°F) ∘ 8 hours at room temperature up to 25°C (77°F) • Do not freeze. • Do not shake. Administration • Administer infusion solution intravenously over 60 minutes through an intravenous line containing a sterile, low-protein binding 0.2 or 0.22 micron in-line filter. • Use separate infusion bags and filters for each drug product. IMFINZI in Combination with Other Products • Administer all intravenous drug products as separate infusions. • Do not co-administer other intravenous drugs through the same infusion line. • For platinum-based chemotherapy, refer to Prescribing Information for administration information. • For pemetrexed therapy, refer to Prescribing Information for administration information. Combination Regimens: Order of Infusions IMFINZI in Combination with Tremelimumab-actl • Infuse tremelimumab-actl first, followed by IMFINZI on the same day of dosing. IMFINZI in Combination with Tremelimumab-actl and Platinum-Based Chemotherapy • Infuse tremelimumab-actl first, followed by IMFINZI and then platinum-based chemotherapy on the day of dosing. IMFINZI in Combination with Tremelimumab-actl and Pemetrexed Therapy • Infuse tremelimumab-actl first, followed by IMFINZI and then pemetrexed therapy on the day of dosing. IMFINZI in Combination with Chemotherapy • Infuse IMFINZI first and then chemotherapy on the same day of dosing. Combination Regimens: Infusion Instructions IMFINZI in Combination with Tremelimumab-actl • Administer tremelimumab-actl over 60 minutes followed by a 60 minute observation period. Then administer IMFINZI as a separate intravenous infusion over 60 minutes. IMFINZI in Combination with Tremelimumab-actl and Platinum-Based Chemotherapy/ Pemetrexed Therapy Cycle 1 • Infuse tremelimumab-actl over 60 minutes. One to two hours after completion of tremelimumab-actl infusion, infuse IMFINZI over 60 minutes. One to two hours after completion of IMFINZI infusion, administer platinum-based chemotherapy. Subsequent Cycles • If there are no infusion reactions during cycle 1, subsequent cycles of IMFINZI can be given immediately after tremelimumab-actl. The time between the end of the IMFINZI infusion and the start of chemotherapy can be reduced to 30 minutes."],"spl_product_data_elements":["IMFINZI Durvalumab DURVALUMAB DURVALUMAB HISTIDINE HISTIDINE MONOHYDROCHLORIDE MONOHYDRATE POLYSORBATE 80 TREHALOSE DIHYDRATE WATER IMFINZI Durvalumab DURVALUMAB DURVALUMAB HISTIDINE HISTIDINE MONOHYDROCHLORIDE MONOHYDRATE POLYSORBATE 80 TREHALOSE DIHYDRATE WATER"],"dosage_forms_and_strengths":["3 DOSAGE FORMS AND STRENGTHS Injection: 120 mg/2.4 mL (50 mg/mL) and 500 mg/10 mL (50 mg/mL) clear to opalescent, colorless to slightly yellow solution in a single-dose vial. • Injection: 500 mg/10 mL (50 mg/mL) solution in a single-dose vial. ( 3 ) • Injection: 120 mg/2.4 mL (50 mg/mL) solution in a single-dose vial. ( 3 )"],"use_in_specific_populations":["8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, IMFINZI can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of IMFINZI in pregnant women. In animal reproduction studies, administration of durvalumab to pregnant cynomolgus monkeys from the confirmation of pregnancy through delivery at exposure levels approximately 6 to 20 times higher than those observed at the clinical dose of 10 mg/kg based on area under the curve (AUC), resulted in an increase in premature delivery, fetal loss, and premature neonatal death ( see Data ). Human immunoglobulin G1 (IgG1) is known to cross the placental barrier; therefore, durvalumab has the potential to be transmitted from the mother to the developing fetus. Apprise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data As reported in the literature, the PD-1/PD-L1 pathway plays a central role in preserving pregnancy by maintaining maternal immune tolerance to the fetus. In mouse allogeneic pregnancy models, disruption of PD-L1 signaling was shown to result in an increase in fetal loss. The effects of durvalumab on prenatal and postnatal development were evaluated in reproduction studies in cynomolgus monkeys. Durvalumab was administered from the confirmation of pregnancy through delivery at exposure levels approximately 6 to 20 times higher than those observed at a clinical dose of 10 mg/kg (based on AUC). Administration of durvalumab resulted in premature delivery, fetal loss (abortion and stillbirth), and increase in neonatal deaths. Durvalumab was detected in infant serum on postpartum Day 1, indicating the presence of placental transfer of durvalumab. Based on its mechanism of action, fetal exposure to durvalumab may increase the risk of developing immune-mediated disorders or altering the normal immune response and immune-mediated disorders have been reported in PD-1 knockout mice. 8.2 Lactation Risk Summary There are no data on the presence of durvalumab in human milk, its effects on the breastfed child, or the effects on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to IMFINZI are unknown. Durvalumab was present in the milk of lactating cynomolgus monkeys and was associated with premature neonatal death (see Data). Because of the potential for adverse reactions in a breastfed child, advise women not to breastfeed during treatment with IMFINZI and for 3 months after the last dose. Refer to the Prescribing Information for the agents administered in combination with IMFINZI for recommended duration to not breastfeed, as appropriate. Data In lactating cynomolgus monkeys, durvalumab was present in breast milk at about 0.15% of maternal serum concentrations after administration of durvalumab from the confirmation of pregnancy through delivery at exposure levels approximately 6 to 20 times higher than those observed at the recommended clinical dose of 10 mg/kg (based on AUC). Administration of durvalumab resulted in premature neonatal death . 8.3 Females and Males of Reproductive Potential Pregnancy testing Verify pregnancy status of females of reproductive potential prior to initiating treatment with IMFINZI. Contraception Females IMFINZI can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment with IMFINZI and for 3 months following the last dose of IMFINZI. Refer to the Prescribing Information for the agents administered in combination with IMFINZI for recommended contraception duration, as appropriate. 8.4 Pediatric Use The safety and effectiveness of IMFINZI have not been established in pediatric patients. Safety and efficacy were assessed but not established in a multi-center, open-label study (NCT03837899) in 45 pediatric patients aged 1 to < 17 years with advanced solid tumors. All 45 patients received at least a single dose of IMFINZI, and 41 patients received IMFINZI in combination with tremelimumab-actl. No new safety signals were observed in pediatric patients in this study. Durvalumab systemic exposure in pediatric patients weighing ≥ 35 kg was within the range of values previously observed in adults given the same weight-based dose, whereas the systemic exposure in pediatric patients weighing < 35 kg was lower than that observed in adults. 8.5 Geriatric Use Of the 401 patients with resectable NSCLC treated with IMFINZI in combination with chemotherapy in the AEGEAN study, 209 (52%) patients were 65 years or older and 49 (12%) patients were 75 years or older. There were no overall clinically meaningful differences in safety or efficacy between patients ≥ 65 years of age and younger patients. Of the 476 patients with unresectable, Stage III NSCLC treated with IMFINZI in the PACIFIC study, 45% were 65 years or older, while 7.6% were 75 years or older. No overall differences in safety or effectiveness were observed between patients 65 years or older and younger patients. The PACIFIC study did not include sufficient numbers of patients aged 75 years and over to determine whether they respond differently from younger patients. Of the 330 patients with metastatic NSCLC treated with IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy, 143 (43%) patients were 65 years or older and 35 (11%) patients were 75 years or older. There were no clinically meaningful differences in safety or efficacy between patients 65 years or older and younger patients. Of the 262 patients with LS-SCLC treated with IMFINZI, 103 (39%) patients were 65 years or older and 15 (6%) patients were 75 years or older. There were no clinically meaningful differences in safety and efficacy between patients 65 years or older and younger patients. Of the 265 patients with ES-SCLC treated with IMFINZI in combination with chemotherapy 101 (38%) patients were 65 years or older and 19 (7.2%) patients were 75 years or older. There were no clinically meaningful differences in safety or efficacy between patients 65 years or older and younger patients. Of the 338 patients with BTC treated with IMFINZI in combination with chemotherapy in the TOPAZ-1 study, 158 (47%) patients were 65 years or older and 38 (11%) patients were 75 years or older. No overall differences in safety or effectiveness of IMFINZI have been observed between patients 65 years of age and older and younger adult patients. Of the 393 patients with uHCC treated with IMFINZI in combination with tremelimumab-actl, 50% of patients were 65 years of age or older and 13% of patients were 75 years of age or older. No overall differences in safety or effectiveness of IMFINZI have been observed between patients 65 years of age and older and younger adult patients. Of the 235 patients with endometrial cancer treated with IMFINZI with carboplatin and paclitaxel, 49% of patients were 65 years of age or older and 12% of patients were 75 years of age or older. No overall differences in safety or effectiveness of IMFINZI have been observed between patients 65 years of age and older and younger adult patients. Of the 530 patients with MIBC treated with IMFINZI in combination with gemcitabine and cisplatin in the NIAGARA study, 272 (51%) patients were 65 years or older, and 57 (11%) patients were 75 years or older. No overall differences in safety or effectiveness of IMFINZI have been observed between patients 65 years of age and older and younger adult patients. Of the 475 patients with resectable GC/GEJC treated with IMFINZI in combination with FLOT chemotherapy in the MATTERHORN study, 184 (39%) patients were 65 years or older and 37 (8%) patients were 75 years or older. No overall differences in safety or effectiveness were observed between patients ≥ 65 years of age and younger adult patients."],"spl_unclassified_section_table":["<table width=\"100%\"><col width=\"33%\"/><col width=\"17%\"/><col width=\"17%\"/><col width=\"33%\"/><tbody><tr><td align=\"center\" colspan=\"4\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">MEDICATION GUIDE</content></paragraph><paragraph>IMFINZI<sup>&#xAE; </sup>(im-FIN-zee)</paragraph><paragraph>(durvalumab)</paragraph><paragraph>injection</paragraph></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">What is the most important information I should know about IMFINZI?</content></paragraph><paragraph>IMFINZI is a medicine that may treat certain cancers by working with your immune system. </paragraph><paragraph>IMFINZI can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended. </paragraph><paragraph><content styleCode=\"bold\">Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including:</content></paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">Lung problems</content>.</item></list></td></tr><tr><td styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>cough</item></list></td><td colspan=\"2\" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>shortness of breath</item></list></td><td styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>chest pain</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">Intestinal problems.</content></item></list></td></tr><tr><td colspan=\"2\" styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>diarrhea (loose stools) or more frequent bowel movements than usual </item><item><caption>&#x2218;</caption>stools that are black, tarry, sticky, or have blood or mucus</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>severe stomach-area (abdomen) pain or tenderness</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">Liver problems.</content></item></list></td></tr><tr><td colspan=\"2\" styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>yellowing of your skin or the whites of your eyes </item><item><caption>&#x2218;</caption>severe nausea or vomiting </item><item><caption>&#x2218;</caption>pain on the right side of your stomach-area (abdomen)</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>dark urine (tea colored) </item><item><caption>&#x2218;</caption>bleeding or bruising more easily than normal</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">Hormone and gland problems.</content></item></list></td></tr><tr><td colspan=\"2\" styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>headaches that will not go away or unusual headaches </item><item><caption>&#x2218;</caption>eye sensitivity to light </item><item><caption>&#x2218;</caption>eye problems </item><item><caption>&#x2218;</caption>rapid heartbeat </item><item><caption>&#x2218;</caption>increase sweating </item><item><caption>&#x2218;</caption>extreme tiredness </item><item><caption>&#x2218;</caption>weight gain or weight loss </item><item><caption>&#x2218;</caption>feeling more hungry or thirsty than usual</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>urinating more often than usual </item><item><caption>&#x2218;</caption>hair loss </item><item><caption>&#x2218;</caption>feeling cold </item><item><caption>&#x2218;</caption>constipation </item><item><caption>&#x2218;</caption>your voice gets deeper </item><item><caption>&#x2218;</caption>dizziness or fainting </item><item><caption>&#x2218;</caption>changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">Kidney problems.</content></item></list></td></tr><tr><td colspan=\"2\" styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>decrease in your amount of urine </item><item><caption>&#x2218;</caption>blood in your urine</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>swelling of your ankles </item><item><caption>&#x2218;</caption>loss of appetite</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">Skin problems.</content></item></list></td></tr><tr><td colspan=\"2\" styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>rash</item><item><caption>&#x2218;</caption>itching</item><item><caption>&#x2218;</caption>skin blistering or peeling</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>painful sores or ulcers in mouth or nose, throat, or genital area</item><item><caption>&#x2218;</caption>fever or flu-like symptoms</item><item><caption>&#x2218;</caption>swollen lymph nodes</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">Pancreas problems.</content></item></list></td></tr><tr><td colspan=\"2\" styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>pain in your upper stomach area (abdomen)</item><item><caption>&#x2218;</caption>severe nausea or vomiting</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>loss of appetite</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with IMFINZI. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include:</content></item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>chest pain, irregular heartbeats, shortness of breath or swelling of ankles</item><item><caption>&#x2218;</caption>confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems </item><item><caption>&#x2218;</caption>tingling, numbness or weakness of the arms or legs</item><item><caption>&#x2218;</caption>double vision, blurry vision, sensitivity to light, eye pain, changes in eye-sight</item><item><caption>&#x2218;</caption>persistent or severe muscle pain or weakness, muscle cramps, joint pain, joint stiffness or swelling</item><item><caption>&#x2218;</caption>low red blood cells, bruising</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">Infusion reactions that can sometimes be severe or life-threatening.</content> Signs and symptoms of infusion reactions may include:</item></list></td></tr><tr><td colspan=\"2\" styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>chills or shaking </item><item><caption>&#x2218;</caption>itching or rash </item><item><caption>&#x2218;</caption>flushing </item><item><caption>&#x2218;</caption>shortness of breath or wheezing</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2218;</caption>dizziness </item><item><caption>&#x2218;</caption>feel like passing out </item><item><caption>&#x2218;</caption>fever </item><item><caption>&#x2218;</caption>back or neck pain</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">Rejection of a transplanted organ or tissue.</content> Your healthcare provider should tell you what signs and symptoms you should report and monitor you depending on the type of organ or tissue transplant that you have had.</item><item><caption>&#x2022;</caption><content styleCode=\"bold\">Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). </content>These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with IMFINZI. Your healthcare provider will monitor you for these complications.</item></list><paragraph><content styleCode=\"bold\">Getting medical treatment right away may help keep these problems from becoming more serious.</content></paragraph><paragraph>Your healthcare provider will check you for these problems during your treatment with IMFINZI. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with IMFINZI, if you have severe side effects.</paragraph></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">What is IMFINZI?</content></paragraph><paragraph><content styleCode=\"bold\">IMFINZI </content>is a prescription medicine used to treat adults with: </paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">a type of lung cancer called non-small cell lung cancer (NSCLC). </content><list listType=\"unordered\"><item><caption>&#x2218;</caption>IMFINZI may be used in combination with chemotherapy that contains platinum prior to surgery and alone after surgery when your NSCLC:<list listType=\"unordered\"><item><caption>&#x25AA;</caption>can be removed by surgery, and</item><item><caption>&#x25AA;</caption>is not known to have an abnormal &#x201C;EGFR&#x201D; or &#x201C;ALK&#x201D; gene.</item></list></item><item><caption>&#x2218;</caption>IMFINZI may be used alone when your NSCLC:<list listType=\"unordered\"><item><caption>&#x25AA;</caption>has not spread outside your chest </item><item><caption>&#x25AA;</caption>cannot be removed by surgery, <content styleCode=\"bold\">and</content></item><item><caption>&#x25AA;</caption>has responded or stabilized with initial treatment with chemotherapy that contains platinum, given at the same time as radiation therapy.</item></list></item><item><caption>&#x2218;</caption>IMFINZI may be used in combination with tremelimumab-actl and chemotherapy that contains platinum when your NSCLC:<list listType=\"unordered\"><item><caption>&#x25AA;</caption>has spread to other parts of your body (metastatic), <content styleCode=\"bold\">and </content></item><item><caption>&#x25AA;</caption>does not have an abnormal &#x201C;EGFR&#x201D; or &#x201C;ALK&#x201D; gene.</item></list></item></list></item><item><caption>&#x2022;</caption><content styleCode=\"bold\">a type of lung cancer called small cell lung cancer (SCLC).</content><list listType=\"unordered\"><item><caption>&#x2218;</caption>for limited-stage small cell lung cancer (LS-SCLC), IMFINZI may be used alone when your LS-SCLC cannot be removed by surgery, <content styleCode=\"bold\">and</content></item><item><caption>&#x2218;</caption>has responded or stabilized after initial treatment with chemotherapy that contains platinum, given at the same time as radiation therapy.</item><item><caption>&#x2218;</caption>for extensive-stage small cell lung cancer (ES-SCLC), IMFINZI may be used with the chemotherapy medicines etoposide and either carboplatin or cisplatin as your first treatment when your ES-SCLC has spread within your lungs or to other parts of the body. </item></list></item><item><caption>&#x2022;</caption><content styleCode=\"bold\">a type of cancer called biliary tract cancer (BTC),</content> including cancer of the bile ducts (cholangiocarcinoma) and gallbladder cancer. IMFINZI may be used in combination with chemotherapy medicines gemcitabine and cisplatin when your BTC:<list listType=\"unordered\"><item><caption>&#x2218;</caption>has spread to nearby tissues (locally advanced), or</item><item><caption>&#x2218;</caption>has spread to other parts of the body (metastatic).</item></list></item><item><caption>&#x2022;</caption><content styleCode=\"bold\">a type of liver cancer that cannot be removed by surgery (unresectable hepatocellular carcinoma or uHCC</content>). IMFINZI is used in combination with tremelimumab-actl to treat uHCC. </item><item><caption>&#x2022;</caption><content styleCode=\"bold\">a type of uterine cancer called endometrial cancer</content>. IMFINZI may be used in combination with chemotherapy medicines carboplatin and paclitaxel followed by IMFINZI alone when your endometrial cancer:<list listType=\"unordered\"><item><caption>&#x2218;</caption>has spread (advanced) or has come back (recurrent), <content styleCode=\"bold\">and</content></item><item><caption>&#x2218;</caption>a laboratory test shows that your tumor is mismatch repair deficient (dMMR).</item></list></item><item><caption>&#x2022;</caption><content styleCode=\"bold\">a type of bladder cancer called muscle invasive bladder cancer (MIBC) that has spread into the muscle layer of the bladder but not to other parts of the body.</content> IMFINZI may be used in combination with gemcitabine and cisplatin (neoadjuvant treatment) prior to the surgical removal of your bladder followed by IMFINZI alone after surgery (adjuvant treatment).</item><item><caption>&#x2022;</caption><content styleCode=\"bold\">A type of stomach cancer called gastric cancer (GC) or gastro-esophageal junction adenocarcinoma (GEJC) that can be removed by surgery. </content>IMFINZI is used in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) prior to and after surgery followed by IMFINZI alone.</item></list><paragraph>It is not known if IMFINZI is safe and effective in children.</paragraph></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Before you receive IMFINZI, tell your healthcare provider about all of your medical conditions, including if you:</content></paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption>have immune system problems such as Crohn&apos;s disease, ulcerative colitis, or lupus</item><item><caption>&#x2022;</caption>have received an organ or tissue transplant, including corneal transplant</item><item><caption>&#x2022;</caption>have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)</item><item><caption>&#x2022;</caption>have received radiation treatment to your chest area</item><item><caption>&#x2022;</caption>have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barr&#xE9; syndrome </item><item><caption>&#x2022;</caption>are pregnant or plan to become pregnant. IMFINZI can harm your unborn baby </item></list><paragraph><content styleCode=\"bold\">Females who are able to become pregnant:</content></paragraph><list listType=\"unordered\"><item><caption> </caption><list listType=\"unordered\"><item><caption>&#x2218;</caption>Your healthcare provider will give you a pregnancy test before you start treatment with IMFINZI.</item><item><caption>&#x2218;</caption>You should use an effective method of birth control during your treatment and for 3 months after the last dose of IMFINZI. Talk to your healthcare provider about birth control methods that you can use during this time.</item><item><caption>&#x2218;</caption>Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with IMFINZI.</item></list></item><item><caption>&#x2022;</caption>are breastfeeding or plan to breastfeed. It is not known if IMFINZI passes into your breast milk. Do not breastfeed during treatment and for 3 months after the last dose of IMFINZI.</item></list><paragraph>Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.</paragraph></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">How will I receive IMFINZI?</content></paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption>Your healthcare provider will give you IMFINZI into your vein through an intravenous (IV) line over 60 minutes.</item><item><caption>&#x2022;</caption>IMFINZI is usually given every 2, 3 or 4 weeks.</item><item><caption>&#x2022;</caption>Your healthcare provider will decide how many treatments you need.</item><item><caption>&#x2022;</caption>Your healthcare provider will test your blood to check you for certain side effects.</item><item><caption>&#x2022;</caption>If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">What are the possible side effects of IMFINZI?</content></paragraph><paragraph>IMFINZI can cause serious side effects, including:</paragraph><paragraph><content styleCode=\"bold\">See &#x201C;What is the most important information I should know about IMFINZI?&#x201D;</content></paragraph><paragraph><content styleCode=\"bold\">The most common side effects of IMFINZI when used with platinum-containing chemotherapy in adults with NSCLC that can be removed by surgery include:</content></paragraph></td></tr><tr><td colspan=\"2\" styleCode=\"Lrule Botrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>low red blood cells (anemia)</item><item><caption>&#x2022;</caption>nausea</item><item><caption>&#x2022;</caption>constipation</item></list></td><td colspan=\"2\" styleCode=\"Rrule Botrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>feeling tired</item><item><caption>&#x2022;</caption>muscle or bone pain </item><item><caption>&#x2022;</caption>rash</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">The most common side effects of IMFINZI when used alone in adults with NSCLC that cannot be removed by surgery include:</content></paragraph></td></tr><tr><td colspan=\"2\" styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>cough</item><item><caption>&#x2022;</caption>feeling tired</item><item><caption>&#x2022;</caption>inflammation in the lungs</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>upper respiratory tract infections</item><item><caption>&#x2022;</caption>shortness of breath</item><item><caption>&#x2022;</caption>rash</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">The most common side effects of IMFINZI when used with tremelimumab-actl and platinum-containing chemotherapy in adults with metastatic NSCLC include:</content></paragraph></td></tr><tr><td colspan=\"2\" styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>nausea</item><item><caption>&#x2022;</caption>feeling tired or weak</item><item><caption>&#x2022;</caption>muscle or bone pain</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>decreased appetite</item><item><caption>&#x2022;</caption>rash</item><item><caption>&#x2022;</caption>diarrhea</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">The most common side effects of IMFINZI when used alone in adults with LS-SCLC include:</content></paragraph></td></tr><tr><td colspan=\"2\" styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>inflammation in the lungs</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>feeling tired or weak</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">The most common side effects of IMFINZI when used with etoposide and either carboplatin or cisplatin in adults with ES-SCLC include:</content></paragraph></td></tr><tr><td colspan=\"2\" styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>nausea</item><item><caption>&#x2022;</caption>hair loss</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>feeling tired or weak</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">The most common side effects of IMFINZI when used with gemcitabine and cisplatin in adults with BTC include:</content></paragraph></td></tr><tr><td colspan=\"2\" styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>feeling tired</item><item><caption>&#x2022;</caption>nausea</item><item><caption>&#x2022;</caption>constipation</item><item><caption>&#x2022;</caption>decreased appetite</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>stomach (abdominal) pain</item><item><caption>&#x2022;</caption>rash</item><item><caption>&#x2022;</caption>fever</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">The most common side effects of IMFINZI when used with tremelimumab-actl in adults with uHCC include:</content></paragraph></td></tr><tr><td colspan=\"2\" styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>rash</item><item><caption>&#x2022;</caption>diarrhea</item><item><caption>&#x2022;</caption>feeling tired</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>itchiness</item><item><caption>&#x2022;</caption>muscle or bone pain</item><item><caption>&#x2022;</caption>stomach (abdominal) pain</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">The most common side effects of IMFINZI when used with carboplatin and paclitaxel in adults with endometrial cancer include:</content></paragraph></td></tr><tr><td colspan=\"2\" styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>inflammation of the nerves causing numbness, weakness, tingling or burning pain of the arms and legs</item><item><caption>&#x2022;</caption>muscle or bone pain</item><item><caption>&#x2022;</caption>nausea</item><item><caption>&#x2022;</caption>hair loss</item><item><caption>&#x2022;</caption>feeling tired</item><item><caption>&#x2022;</caption>stomach (abdominal) pain</item><item><caption>&#x2022;</caption>constipation</item><item><caption>&#x2022;</caption>rash</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>decreased level of magnesium in the blood </item><item><caption>&#x2022;</caption>increased liver function tests</item><item><caption>&#x2022;</caption>diarrhea</item><item><caption>&#x2022;</caption>vomiting</item><item><caption>&#x2022;</caption>cough</item><item><caption>&#x2022;</caption>decreased level of potassium in the blood</item><item><caption>&#x2022;</caption>shortness of breath</item><item><caption>&#x2022;</caption>headache</item><item><caption>&#x2022;</caption>increased level of alkaline phosphatase in the blood</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">The most common side effects of IMFINZI when used with gemcitabine and cisplatin in adults with MIBC include:</content></paragraph></td></tr><tr><td colspan=\"2\" styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>decreased red blood cells (anemia)</item><item><caption>&#x2022;</caption>decreased white blood cells</item><item><caption>&#x2022;</caption>increased level of creatinine in the blood</item><item><caption>&#x2022;</caption>decreased level of sodium in the blood</item><item><caption>&#x2022;</caption>nausea</item><item><caption>&#x2022;</caption>increased liver function tests</item><item><caption>&#x2022;</caption>decreased level of calcium in the blood</item><item><caption>&#x2022;</caption>decreased blood platelet counts</item><item><caption>&#x2022;</caption>feeling tired</item><item><caption>&#x2022;</caption>increased level of potassium in the blood</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>decreased lymphocyte counts </item><item><caption>&#x2022;</caption>constipation</item><item><caption>&#x2022;</caption>decreased level of magnesium in the blood</item><item><caption>&#x2022;</caption>decreased appetite</item><item><caption>&#x2022;</caption>increased level of alkaline phosphatase in the blood</item><item><caption>&#x2022;</caption>rash</item><item><caption>&#x2022;</caption>fever</item><item><caption>&#x2022;</caption>diarrhea</item><item><caption>&#x2022;</caption>vomiting</item><item><caption>&#x2022;</caption>stomach (abdominal) pain</item></list></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">The most common side effects of IMFINZI when used with FLOT in adults with GC or GEJC include: </content></paragraph><paragraph>Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</paragraph><paragraph>These are not all of the possible side effects of IMFINZI. Ask your healthcare provider or pharmacist for more information.</paragraph><paragraph>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</paragraph></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">General information about the safe and effective use of IMFINZI.</content></paragraph><paragraph>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. If you would like more information about IMFINZI, talk with your healthcare provider. You can ask your healthcare provider for information about IMFINZI that is written for health professionals.</paragraph></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">What are the ingredients in IMFINZI?</content></paragraph><paragraph><content styleCode=\"bold\">Active ingredient:</content> durvalumab</paragraph><paragraph><content styleCode=\"bold\">Inactive ingredients: </content>L-histidine, L-histidine hydrochloride monohydrate, &#x3B1;,&#x3B1;-trehalose dihydrate, polysorbate 80, Water for Injection, USP.</paragraph></td></tr><tr><td colspan=\"4\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Manufactured for: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850</paragraph><paragraph>By: AstraZeneca UK Limited, 1 Francis Crick Ave. Cambridge, England CB2 0AA US License No. 2043</paragraph><paragraph>IMFINZI is a registered trademark of AstraZeneca group of companies.</paragraph><paragraph>For more information, call 1-800-236-9933 or go to <linkHtml href=\"https://www.imfinzi.com/\">www.IMFINZI.com</linkHtml></paragraph><paragraph>&#xA9; AstraZeneca 2025</paragraph></td></tr></tbody></table>"],"dosage_and_administration_table":["<table styleCode=\"Noautorules\" width=\"100%\"><caption>Table 1. Recommended Dosages of IMFINZI</caption><col width=\"34%\"/><col width=\"34%\"/><col width=\"31%\"/><thead><tr><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Indication</content></th><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Recommended IMFINZI Dosage</content></th><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Duration of Therapy</content></th></tr></thead><tbody><tr><th align=\"left\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><content styleCode=\"xmChange\">Neoadjuvant and Adjuvant Treatment of Resectable NSCLC</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"xmChange\">Patients with a body weight of &#x2265; 30 kg:</content> <content styleCode=\"xmChange\">Neoadjuvant: IMFINZI 1,500 mg in combination with chemotherapy</content><footnote ID=\"_Ref175035855\">Administer IMFINZI prior to chemotherapy on the same day. Refer to the Prescribing Information for the agent administered in combination with IMFINZI for recommended dosage information, as appropriate.</footnote><content styleCode=\"xmChange\"> every 3 weeks for up to 4 cycles prior to surgery </content> <content styleCode=\"xmChange\">Adjuvant: IMFINZI 1,500 mg as a single agent every 4 weeks for up to 12 cycles after surgery.</content> Patients with a body weight of &lt; 30 kg: Neoadjuvant: IMFINZI 20 mg/kg every 3 weeks in combination with chemotherapy<footnoteRef IDREF=\"_Ref175035855\"/> for up to 4 cycles prior to surgery. Adjuvant: IMFINZI 20 mg/kg every 4 weeks for up to 12 cycles as a single agent after surgery.</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"xmChange\">Until disease progression that precludes definitive surgery, recurrence, unacceptable toxicity, or a maximum of 12 cycles after surgery</content></th></tr><tr><th align=\"left\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\">Unresectable Stage III NSCLC</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">Following concurrent platinum-based chemotherapy and radiation therapy: Patients with a body weight of &#x2265; 30 kg: 10 mg/kg every 2 weeks  or  1,500 mg every 4 weeks Patients with a body weight of &lt; 30 kg: 10 mg/kg every 2 weeks</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">Until disease progression, unacceptable toxicity, or a maximum of 12 months</th></tr><tr><th align=\"left\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\">Limited Stage SCLC</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">Following concurrent platinum-based chemotherapy and radiation therapy:  Patients with a body weight of &#x2265; 30 kg: <content styleCode=\"xmChange\">1,500 mg every 4 weeks</content> Patients with a body weight of &lt; 30 kg: <content styleCode=\"xmChange\">20 mg/kg every 4 weeks</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">Until disease progression, unacceptable toxicity, or a maximum of 24 months</th></tr><tr><th align=\"left\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\">Extensive Stage SCLC</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">Patients with a body weight of &#x2265; 30 kg: 1,500 mg in combination with chemotherapy<footnoteRef IDREF=\"_Ref175035855\"/> every 3 weeks (21 days) for 4 cycles, followed by 1,500 mg every 4 weeks as a single agent Patients with a body weight of &lt; 30 kg: 20 mg/kg in combination with chemotherapy<footnoteRef IDREF=\"_Ref175035855\"/> every 3 weeks (21 days) for 4 cycles, followed by 10 mg/kg every 2 weeks as a single agent</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">Until disease progression or until unacceptable toxicity</th></tr><tr><th align=\"left\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\">BTC</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">Patients with a body weight of &#x2265; 30 kg: 1,500 mg in combination with chemotherapy<footnoteRef IDREF=\"_Ref175035855\"/> every 3 weeks (21 days) up to 8 cycles followed by 1,500 mg every 4 weeks as a single agent Patients with a body weight of &lt; 30 kg: 20 mg/kg in combination with chemotherapy<footnoteRef IDREF=\"_Ref175035855\"/> every 3 weeks (21 days) up to 8 cycles, followed by 20 mg/kg every 4 weeks as a single agent</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">Until disease progression or until unacceptable toxicity</th></tr><tr><th align=\"left\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\">uHCC</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">Patients with a body weight of &#x2265; 30 kg: IMFINZI 1,500 mg following a single dose of tremelimumab-actl<footnote ID=\"_Ref175036061\">Administer tremelimumab-actl prior to IMFINZI on the same day. When tremelimumab-actl is administered in combination with IMFINZI, refer to the Prescribing Information for tremelimumab-actl dosing information.</footnote> 300 mg at Day 1 of Cycle 1; Continue IMFINZI 1,500 mg as a single agent every 4 weeks Patients with a body weight of &lt; 30 kg: IMFINZI 20 mg/kg following a single dose of tremelimumab-actl<footnoteRef IDREF=\"_Ref175036061\"/> 4 mg/kg at Day 1 of Cycle 1; Continue IMFINZI 20 mg/kg as a single agent every 4 weeks</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">After Cycle 1 of combination therapy, administer IMFINZI as a single agent every 4 weeks until disease progression or unacceptable toxicity</th></tr><tr><th align=\"left\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><content styleCode=\"xmChange\">dMMR endometrial cancer</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"xmChange\">Patients with a body weight of &#x2265; 30 kg:</content> <content styleCode=\"xmChange\">IMFINZI 1,120 mg in combination with carboplatin and paclitaxel</content><footnoteRef IDREF=\"_Ref175035855\"/><content styleCode=\"xmChange\"> every 3 weeks (21 days) for 6 cycles, followed by IMFINZI 1,500 mg every 4 weeks as a single agent</content> <content styleCode=\"xmChange\">Patients with a body weight of &lt; 30 kg:</content> <content styleCode=\"xmChange\">IMFINZI 15 mg/kg in combination with carboplatin and paclitaxel</content><footnoteRef IDREF=\"_Ref175035855\"/><content styleCode=\"xmChange\"> every 3 weeks (21 days) for 6 cycles, followed by IMFINZI 20 mg/kg every 4 weeks as a single agent</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"xmChange\">Until disease progression or unacceptable toxicity</content></th></tr><tr><th align=\"left\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><content styleCode=\"xmChange\">Neoadjuvant and Adjuvant Treatment of MIBC</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"xmChange\">Patients with a body weight of &#x2265;30 kg:</content> <content styleCode=\"xmChange\">Neoadjuvant: 1,500 mg in combination with gemcitabine and cisplatin</content><footnoteRef IDREF=\"_Ref175035855\"/><content styleCode=\"xmChange\"> every 3 weeks for 4 cycles prior to surgery</content> <content styleCode=\"xmChange\">Adjuvant: IMFINZI 1,500 mg as a single agent every 4 weeks for up to 8 cycles after surgery</content> <content styleCode=\"xmChange\">Patients with a body weight of &lt; 30 kg:</content> <content styleCode=\"xmChange\">Neoadjuvant: 20 mg/kg in combination with gemcitabine and cisplatin</content><footnoteRef IDREF=\"_Ref175035855\"/><content styleCode=\"xmChange\"> every 3 weeks for 4 cycles prior to surgery</content> <content styleCode=\"xmChange\">Adjuvant: IMFINZI 20 mg/kg as a single agent every 4 weeks for up to 8 cycles after surgery</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"xmChange\">Until disease progression that precludes definitive surgery, recurrence, or unacceptable toxicity or a maximum of 8 cycles after surgery</content></th></tr><tr><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"xmChange\">Neoadjuvant and Adjuvant </content> <content styleCode=\"xmChange\">Treatment of Resectable </content> <content styleCode=\"xmChange\">GC/GEJC</content></th><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"xmChange\">Patients with a body weight of &#x2265; 30 </content> <content styleCode=\"xmChange\">kg: </content> <content styleCode=\"xmChange\">Neoadjuvant: IMFINZI 1,500 mg every 4 weeks with FLOT</content><footnoteRef IDREF=\"_Ref175035855\"/><footnote ID=\"_Ref215139877\">FLOT chemotherapy is administered on days 1 and 15 of each 4 week cycle <content styleCode=\"italics\">[See Clinical Studies (<linkHtml href=\"#ID_2283848c-062c-48a9-90ee-30ad9dfcefdc\">14.7</linkHtml>)]</content>.</footnote><content styleCode=\"xmChange\"> for up to 2 cycles prior to surgery</content> <content styleCode=\"xmChange\">Adjuvant: IMFINZI 1,500 mg every 4 weeks with FLOT</content><footnoteRef IDREF=\"_Ref175035855\"/><footnoteRef IDREF=\"_Ref215139877\"/><content styleCode=\"xmChange\"> for up to 2 cycles, followed by IMFINZI 1,500 mg as a single agent every 4 weeks for up to 10 cycles</content> <content styleCode=\"xmChange\">Patients with a body weight of &lt; 30 kg:</content> <content styleCode=\"xmChange\">Neoadjuvant: IMFINZI 20 mg/kg every 4 weeks with FLOT*&#xB1; for up to 2 cycles prior to surgery</content> <content styleCode=\"xmChange\">Adjuvant: IMFINZI 20 mg/kg every 4 weeks with FLOT</content><footnoteRef IDREF=\"_Ref175035855\"/><footnoteRef IDREF=\"_Ref215139877\"/><content styleCode=\"xmChange\"> for up to 2 cycles, followed by IMFINZI 20 mg/kg as a single agent every 4 weeks for up to 10 cycles</content></th><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"xmChange\">Neoadjuvant: Until disease progression that precludes definitive surgery or unacceptable toxicity</content></th></tr></tbody></table>","<table styleCode=\"Noautorules\" width=\"100%\"><caption>Table 2. Recommended Dosage Schedule for Metastatic NSCLC</caption><col width=\"13%\"/><col width=\"3%\"/><col width=\"3%\"/><col width=\"3%\"/><col width=\"3%\"/><col width=\"3%\"/><col width=\"3%\"/><col width=\"3%\"/><col width=\"3%\"/><col width=\"3%\"/><col width=\"3%\"/><col width=\"4%\"/><col width=\"4%\"/><col width=\"4%\"/><col width=\"4%\"/><col width=\"4%\"/><col width=\"4%\"/><col width=\"4%\"/><col width=\"4%\"/><col width=\"4%\"/><col width=\"4%\"/><col width=\"4%\"/><col width=\"4%\"/><col width=\"4%\"/><col width=\"4%\"/><col width=\"4%\"/><thead><tr><th align=\"left\" rowspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><th align=\"center\" colspan=\"25\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Week</content><footnote ID=\"_Ref170130582\">continue IMFINZI until disease progression or intolerable toxicity.</footnote><footnote ID=\"_Ref170130594\">note the dosing interval change from every 3 weeks to every 4 weeks starting at cycle 5.</footnote></th></tr><tr><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">0</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">1</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">2</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">3</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">4</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">5</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">6</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">7</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">8</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">9</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">10</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">11</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">12</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">13</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">14</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">15</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">16</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">17</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">18</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">19</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">20</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">21</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">22</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">23</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">24</th></tr><tr><th align=\"left\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><content styleCode=\"bold\">Cycle:</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">1</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">2</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">3</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">4</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">5</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">6</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">7</th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\">8</th></tr></thead><tbody><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>IMFINZI<footnoteRef IDREF=\"_Ref170130582\"/><footnote ID=\"_Ref170130623\">intravenous infusion over 60 minutes <content styleCode=\"italics\">[see </content><content styleCode=\"italics\"><linkHtml href=\"#ID_5FAE5FC7-16A6-40AA-BE1A-F9C8C5CF087B\">Dosage and Administration (2.4)</linkHtml></content><content styleCode=\"italics\">]</content>.</footnote></paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>X</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>X</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>X</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>X</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>X</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>X</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>X</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>X</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Tremelimumab-actl<footnoteRef IDREF=\"_Ref170130623\"/><footnote ID=\"_Ref170130659\">if patients receive fewer than 4 cycles of platinum-based chemotherapy, the remaining cycles of tremelimumab-actl (up to a total of 5) should be given after the platinum-based chemotherapy phase, in combination with IMFINZI, every 4 weeks.</footnote></paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>X</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>X</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>X</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>X</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>X</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Chemotherapy</paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>X</paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>X</paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>X</paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>X</paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>X<footnote ID=\"_Ref170128259\">optional pemetrexed therapy from week 12 until disease progression or intolerable toxicity for patients with non-squamous disease who received treatment with pemetrexed and carboplatin/cisplatin.</footnote></paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>X<footnoteRef IDREF=\"_Ref170128259\"/></paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>X<footnoteRef IDREF=\"_Ref170128259\"/></paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>X<footnoteRef IDREF=\"_Ref170128259\"/></paragraph></td></tr></tbody></table>","<table styleCode=\"Noautorules\" width=\"100%\"><caption>Table 3. Recommended Regimen and Dosage for Metastatic NSCLC</caption><col width=\"20%\"/><col width=\"19%\"/><col width=\"17%\"/><col width=\"17%\"/><col width=\"26%\"/><thead><tr><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Tumor Histology</content></th><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Patient Weight</content></th><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">IMFINZI Dosage</content></th><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Tremelimumab-actl Dosage<footnote ID=\"_Ref170129578\">Refer to the Prescribing Information for dosing information.</footnote></content></th><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Platinum-based Chemotherapy Regimen<footnoteRef IDREF=\"_Ref170129578\"/></content></th></tr></thead><tbody><tr><td rowspan=\"2\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Non-Squamous</content></paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>&#x2265; 30 kg</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1,500 mg</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>75 mg</paragraph></td><td rowspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>carboplatin &amp; nab-paclitaxel </item></list><paragraph>OR</paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption>carboplatin or cisplatin &amp; pemetrexed</item></list></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>&lt; 30 kg</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>20 mg/kg</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1 mg/kg</paragraph></td></tr><tr><td rowspan=\"2\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Squamous</content></paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>&#x2265; 30 kg</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1,500 mg</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>75 mg</paragraph></td><td rowspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>carboplatin &amp; nab-paclitaxel</item></list><paragraph>OR</paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption>carboplatin or cisplatin &amp; gemcitabine</item></list></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>&lt; 30 kg</paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>20 mg/kg</paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>1 mg/kg</paragraph></td></tr></tbody></table>","<table cellpadding=\"0pt\" width=\"100%\"><caption>Table 4. Recommended Dosage Modifications for Adverse Reactions</caption><col width=\"34%\"/><col width=\"27%\"/><col width=\"39%\"/><thead><tr><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Adverse Reaction</content></th><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Severity</content><footnote ID=\"_Ref215750583\">Based on National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03.</footnote></th><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Dosage Modification</content></th></tr></thead><tbody><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">Immune-Mediated Adverse Reactions <content styleCode=\"italics\">[see <linkHtml href=\"#ID_9BE33FBA-5758-4063-A020-F502CCA119D4\">Warnings and Precautions (5.1)</linkHtml>]</content></content></paragraph></td></tr><tr><td rowspan=\"2\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><list listType=\"ordered\"><item><caption> </caption>Pneumonitis </item></list></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Grade 2</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Withhold<footnote ID=\"_Ref215751040\">Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids or an inability to reduce corticosteroid dose to 10 mg of prednisone or less per day (or equivalent) within 12 weeks of initiating corticosteroids.</footnote></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Grade 3 or 4</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Permanently discontinue</paragraph></td></tr><tr><td rowspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><list listType=\"ordered\"><item><caption> </caption>Colitis</item></list></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Grade 2</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Withhold<footnoteRef IDREF=\"_Ref215751040\"/></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Grade 3</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Withhold<footnoteRef IDREF=\"_Ref215751040\"/> or permanently discontinue<footnote ID=\"_Ref215751744\">Permanently discontinue IMFINZI for Grade 3 colitis when administered as part of a tremelimumab-actl containing regimen.</footnote></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Grade 4</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Permanently discontinue</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><list listType=\"ordered\"><item><caption> </caption>Intestinal perforation</item></list></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Any grade</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Permanently discontinue</paragraph></td></tr><tr><td rowspan=\"2\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><list listType=\"ordered\"><item><caption> </caption>Hepatitis with no tumor involvement of the liver</item></list></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>ALT or AST increases to more than 3 and up to 8 times the ULN</paragraph><paragraph>or</paragraph><paragraph>total bilirubin increases to more than 1.5 and up to 3 times ULN</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Withhold<footnoteRef IDREF=\"_Ref215751040\"/></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>ALT or AST increases to more than 8 times ULN</paragraph><paragraph>or</paragraph><paragraph>total bilirubin increases to more than 3 times the ULN</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Permanently discontinue</paragraph></td></tr><tr><td rowspan=\"2\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><list listType=\"ordered\"><item><caption> </caption>Hepatitis with tumor involvement of the liver<footnote ID=\"_Ref215752243\">If AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue IMFINZI based on recommendations for hepatitis with no liver involvement.</footnote></item></list></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>AST or ALT is more than 1 and up to 3 times ULN at baseline and increases to more than 5 and up to 10 times ULN </paragraph><paragraph>or</paragraph><paragraph>AST or ALT is more than 3 and up to 5 times ULN at baseline and increases to more than 8 and up to 10 times ULN</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Withhold<footnoteRef IDREF=\"_Ref215751040\"/></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>AST or ALT increases to more than 10 times ULN</paragraph><paragraph>or</paragraph><paragraph>total bilirubin increases to more than 3 times ULN</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Permanently discontinue</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><list listType=\"ordered\"><item><caption> </caption>Endocrinopathies</item></list></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Grade 3 or 4</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Withhold until clinically stable or permanently discontinue depending on severity</paragraph></td></tr><tr><td rowspan=\"2\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><list listType=\"ordered\"><item><caption> </caption>Nephritis with Renal Dysfunction</item></list></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Grade 2 or 3 increased blood creatinine</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Withhold<footnoteRef IDREF=\"_Ref215751040\"/></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Grade 4 increased blood creatinine</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Permanently discontinue</paragraph></td></tr><tr><td rowspan=\"2\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><list listType=\"ordered\"><item><caption> </caption>Exfoliative Dermatologic Conditions</item></list></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Suspected SJS, TEN, or DRESS</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Withhold<footnoteRef IDREF=\"_Ref215751040\"/></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Confirmed SJS, TEN, or DRESS</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Permanently discontinue</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><list listType=\"ordered\"><item><caption> </caption>Myocarditis</item></list></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Grade 2, 3, or 4</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Permanently discontinue</paragraph></td></tr><tr><td rowspan=\"2\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><list listType=\"ordered\"><item><caption> </caption>Neurological Toxicities</item></list></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Grade 2</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Withhold<footnoteRef IDREF=\"_Ref215751040\"/></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Grade 3 or 4</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Permanently discontinue</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">Other Adverse Reactions</content></paragraph></td></tr><tr><td rowspan=\"2\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><list listType=\"ordered\"><item><caption> </caption>Infusion-related reactions <content styleCode=\"italics\">[see <linkHtml href=\"#_5.2_Infusion-Related_Reactions\">Warnings and Precautions (5.2)</linkHtml>]</content></item></list></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Grade 1 or 2</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Interrupt or slow the rate of infusion</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Grade 3 or 4</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"middle\"><paragraph>Permanently discontinue</paragraph></td></tr><tr><td colspan=\"3\" valign=\"middle\"><paragraph>ALT = alanine aminotransferase, AST = aspartate aminotransferase, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson Syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit normal.</paragraph></td></tr></tbody></table>"],"animal_pharmacology_and_or_toxicology":["13.2 Animal Toxicology and/or Pharmacology In animal models, inhibition of PD-L1/PD-1 signaling increased the severity of some infections and enhanced inflammatory responses. Mycobacterium tuberculosis -infected PD-1 knockout mice exhibit markedly decreased survival compared with wild-type controls, which correlated with increased bacterial proliferation and inflammatory responses in these animals. PD-1 blockade using a primate anti-PD-1 antibody was also shown to exacerbate M. tuberculosis infection in rhesus macaques. PD-L1 and PD-1 knockout mice and mice receiving PD-L1 blocking antibody have also shown decreased survival following infection with lymphocytic choriomeningitis virus."],"package_label_principal_display_panel":["PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 0310-4500-12 Rx only IMFINZI™ (durvalumab) Injection 120 mg/2.4 mL (50 mg/mL) For Intravenous Infusion After Dilution Single-dose vial. Discard unused portion. Store at 2° to 8°C (36° to 46°F). Do not freeze or shake. Keep vial in original carton to protect from light. Attention Pharmacist: Dispense the accompanying Medication Guide to each patient. Do not use if vial seal is broken or missing. Must dilute before use. See prescribing information. AstraZeneca 0310450012","PACKAGE/LABEL DISPLAY PANEL NDC 0310-4611-50 Rx only IMFINZI™ (durvalumab) Injection 500 mg/10 mL (50 mg/mL) For Intravenous Infusion After Dilution Single-dose vial. Discard unused portion. Store at 2° to 8°C (36° to 46°F). Do not freeze or shake. Keep vial in original carton to protect from light. Attention Pharmacist: Dispense the accompanying Medication Guide to each patient. Do not use if vial seal is broken or missing. Must dilute before use. See prescribing information. AstraZeneca 0310461150"],"carcinogenesis_and_mutagenesis_and_impairment_of_fertility":["13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenic and genotoxic potential of durvalumab have not been evaluated. Animal fertility studies have not been conducted with durvalumab. In repeat-dose toxicology studies with durvalumab in sexually mature cynomolgus monkeys of up to 3 months duration, there were no notable effects on the male and female reproductive organs."]},"tags":[{"label":"Programmed Death Ligand-1 Blocker","category":"class"},{"label":"Monoclonal Antibody","category":"modality"},{"label":"Programmed cell death 1 ligand 1","category":"target"},{"label":"CD274","category":"gene"},{"label":"L01FF03","category":"atc"},{"label":"Intravenous","category":"route"},{"label":"Injection","category":"form"},{"label":"Active","category":"status"},{"label":"Extensive stage primary small cell carcinoma of lung","category":"indication"},{"label":"Liver cell carcinoma","category":"indication"},{"label":"Metastatic carcinoma to biliary tract","category":"indication"},{"label":"Non-small cell lung cancer","category":"indication"},{"label":"Small cell carcinoma of lung","category":"indication"},{"label":"Transitional cell carcinoma","category":"indication"},{"label":"Astrazeneca Uk Ltd","category":"company"},{"label":"Approved 2010s","category":"decade"},{"label":"Antineoplastic Agents","category":"pharmacology"},{"label":"Antineoplastic Agents, Immunological","category":"pharmacology"}],"phase":"marketed","safety":{"boxedWarnings":[],"safetySignals":[{"date":"","signal":"DEATH","source":"FDA FAERS","actionTaken":"3167 reports"},{"date":"","signal":"MALIGNANT NEOPLASM PROGRESSION","source":"FDA FAERS","actionTaken":"1390 reports"},{"date":"","signal":"PNEUMONITIS","source":"FDA FAERS","actionTaken":"819 reports"},{"date":"","signal":"RADIATION PNEUMONITIS","source":"FDA FAERS","actionTaken":"793 reports"},{"date":"","signal":"PYREXIA","source":"FDA FAERS","actionTaken":"574 reports"},{"date":"","signal":"DIARRHOEA","source":"FDA FAERS","actionTaken":"538 reports"},{"date":"","signal":"OFF LABEL USE","source":"FDA FAERS","actionTaken":"481 reports"},{"date":"","signal":"DYSPNOEA","source":"FDA FAERS","actionTaken":"435 reports"},{"date":"","signal":"INTERSTITIAL LUNG DISEASE","source":"FDA FAERS","actionTaken":"432 reports"},{"date":"","signal":"PNEUMONIA","source":"FDA FAERS","actionTaken":"413 reports"}],"commonSideEffects":[{"effect":"Pneumonitis/Radiation Pneumonitis","drugRate":"","severity":"serious","_validated":false,"_confidence":0.3},{"effect":"Cough","drugRate":"40%","severity":"serious","_validated":true},{"effect":"Fatigue","drugRate":"34%","severity":"serious","_validated":true},{"effect":"Dyspnea","drugRate":"","severity":"serious","_validated":false,"_confidence":0.3},{"effect":"Upper respiratory tract infections","drugRate":"","severity":"serious","_validated":false,"_confidence":0.3},{"effect":"Rash","drugRate":"","severity":"serious","_validated":false,"_confidence":0.3},{"effect":"Pneumonia","drugRate":"12.6%","severity":"serious","_validated":true},{"effect":"Diarrhea","drugRate":"","severity":"common","_validated":false,"_confidence":0.3},{"effect":"Abdominal pain","drugRate":"","severity":"common","_validated":false,"_confidence":0.3},{"effect":"Hypothyroidism","drugRate":"","severity":"common","_validated":false,"_confidence":0.3},{"effect":"Pruritus","drugRate":"12%","severity":"common","_validated":true},{"effect":"Nausea","drugRate":"≥20%","severity":"serious","_validated":true},{"effect":"Alopecia","drugRate":"≥20%","severity":"serious","_validated":true},{"effect":"Pyrexia","drugRate":"9%","severity":"mild","_validated":true},{"effect":"Laryngitis","drugRate":"2.6%","severity":"mild","_validated":true},{"effect":"Nasopharyngitis","drugRate":"2.9%","severity":"mild","_validated":true},{"effect":"Peritonsillar abscess","drugRate":"2%","severity":"mild","_validated":true},{"effect":"Rhinitis","drugRate":"2.6%","severity":"mild","_validated":true},{"effect":"Sinusitis","drugRate":"2.6%","severity":"mild","_validated":true},{"effect":"Tonsillitis","drugRate":"2.6%","severity":"mild","_validated":true},{"effect":"Tracheobronchitis","drugRate":"2.6%","severity":"mild","_validated":true},{"effect":"Dysphonia","drugRate":"<5%","severity":"mild","_validated":true},{"effect":"Dysuria","drugRate":"<5%","severity":"mild","_validated":true},{"effect":"Night sweats","drugRate":"<5%","severity":"mild","_validated":true},{"effect":"Peripheral edema","drugRate":"<5%","severity":"mild","_validated":true},{"effect":"Increased susceptibility to infections","drugRate":"<5%","severity":"mild","_validated":true}],"specialPopulations":{"Pregnancy":"Based on its mechanism of action and data from animal studies, IMFINZI can cause fetal harm when administered to pregnant woman [see Clinical Pharmacology (12.1)]. There are no data on the use of IMFINZI in pregnant women.In animal reproduction studies, administration of durvalumab to pregnant cynomolgus monkeys from the confirmation of pregnancy through delivery resulted in an increase in premature delivery, fetal loss, and premature neonatal death (see Data). Human immunoglobulin G1 (IgG1) is known to cross the placental barrier; therefore, durvalumab has the potential to be transmitted from the mother to the developing fetus. Apprise pregnant women of the potential risk to fetus.In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.DataAnimal DataAs reported in the literature, the PD-1/PD-L1 pathway plays central role in preserving pregnancy by maintaining maternal immune tolerance to the fetus. In mouse allogeneic pregnancy models, disruption of PD-L1 signaling was shown to result in an increase in fetal loss. The effects of durvalumab on prenatal and postnatal development were evaluated in reproduction studies in cynomolgus monkeys. Durvalumab was administered from the confirmation of pregnancy through delivery at exposure levels approximately to 20 times hi","Geriatric use":"Of the 476 patients treated with IMFINZI in the PACIFIC study, 45% were 65 years or older, while 7.6% were 75 years or older. No overall differences in safety or effectiveness were observed between patients 65 years or older and younger patients. The PACIFIC study did not include sufficient numbers of patients aged 75 years and over to determine whether they respond differently from younger patients.Of the 265 patients with ES-SCLC treated with IMFINZI in combination with chemo","Paediatric use":"The safety and effectiveness of IMFINZI have not been established in pediatric patients."}},"trials":[],"aliases":[],"company":"AstraZeneca","patents":[],"pricing":[],"_fixedAt":"2026-03-30T11:34:53.314808","_sources":{"trials":{"url":"https://clinicaltrials.gov/search?intr=durvalumab","method":"api_direct","source":"ClinicalTrials.gov","rawText":"","confidence":1,"sourceType":"ctgov","retrievedAt":"2026-04-19T23:44:21.469283+00:00"},"timeline":{"url":"https://en.wikipedia.org/wiki/Durvalumab","method":"deterministic","source":"Wikipedia","rawText":"","confidence":0.8,"sourceType":"wikipedia","retrievedAt":"2026-04-19T23:44:29.825346+00:00"},"regulatory.ca":{"url":"","method":"api_direct","source":"Health Canada DPD","rawText":"","confidence":1,"sourceType":"health_canada_dpd","retrievedAt":"2026-04-19T23:44:28.457463+00:00"},"regulatory.eu":{"url":"","method":"api_direct","source":"European Medicines Agency","rawText":"","confidence":1,"sourceType":"ema_api","retrievedAt":"2026-04-19T23:44:21.495619+00:00"},"regulatory.us":{"url":"","method":"api_direct","source":"FDA Drugs@FDA","rawText":"","confidence":1,"sourceType":"fda_drugsfda","retrievedAt":"2026-04-19T23:44:16.741280+00:00"},"publicationCount":{"url":"https://pubmed.ncbi.nlm.nih.gov/?term=durvalumab","method":"api_direct","source":"PubMed/NCBI","rawText":"","confidence":1,"sourceType":"pubmed","retrievedAt":"2026-04-19T23:44:29.225475+00:00"},"mechanism.drugClass":{"url":"https://api.fda.gov/drug/label.json","method":"deterministic","source":"FDA Label (EPC)","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T23:44:15.261023+00:00"},"administration.route":{"url":"","method":"deterministic","source":"FDA Label","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T23:44:15.261081+00:00"},"safety.boxedWarnings":{"url":"","method":"deterministic","source":"FDA Label (no boxed warning)","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T23:44:15.261095+00:00"},"safety.safetySignals":{"url":"https://api.fda.gov/drug/event.json","method":"api_direct","source":"FDA FAERS","rawText":"","confidence":1,"sourceType":"fda_faers","retrievedAt":"2026-04-19T23:44:30.916160+00:00"},"mechanism.target_chembl":{"url":"","method":"api_direct","source":"ChEMBL mechanism: Programmed cell death 1 ligand 1 inhibitor","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-19T23:44:29.825203+00:00"},"crossReferences.chemblId":{"url":"https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL3301587/","method":"api_direct","source":"ChEMBL (EMBL-EBI)","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-19T23:44:29.721287+00:00"},"regulatory.fda_application":{"url":"","method":"deterministic","source":"FDA Label","rawText":"BLA761069","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T23:44:15.261105+00:00"}},"allNames":"imfinzi, medi4736","offLabel":[],"synonyms":["durvalumab","MEDI4736","MEDI 4736","imfinzi","durvalumab (genetical recombination)"],"timeline":[{"date":"2017-05-01","type":"positive","source":"DrugCentral","milestone":"FDA approval (Astrazeneca Uk Ltd)"},{"date":"2018-07-02","type":"positive","source":"DrugCentral","milestone":"PMDA approval (AstraZeneca KK)"},{"date":"2018-09-21","type":"positive","source":"DrugCentral","milestone":"EMA approval (Astrazeneca Ab)"}],"aiSummary":"Imfinzi (durvalumab) is a programmed death ligand-1 blocker developed by AstraZeneca UK Ltd. It targets the PD-L1 protein to prevent cancer cells from evading the immune system. Imfinzi is approved to treat various types of cancer, including non-small cell lung cancer, small cell lung cancer, and liver cell carcinoma. The drug is patented and commercially available. Key safety considerations include immune-mediated adverse reactions and infusion-related reactions.","brandName":"Imfinzi","ecosystem":[{"indication":"Extensive stage primary small cell carcinoma of lung","otherDrugs":[{"name":"atezolizumab","slug":"atezolizumab","company":"Genentech Inc"}],"globalPrevalence":null},{"indication":"Liver cell carcinoma","otherDrugs":[{"name":"atezolizumab","slug":"atezolizumab","company":"Genentech Inc"},{"name":"bevacizumab","slug":"bevacizumab","company":"Genentech"},{"name":"cabozantinib","slug":"cabozantinib","company":"Exelixis"},{"name":"lenvatinib","slug":"lenvatinib","company":"Eisai Inc"}],"globalPrevalence":null},{"indication":"Metastatic carcinoma to biliary tract","otherDrugs":[],"globalPrevalence":null},{"indication":"Non-small cell lung cancer","otherDrugs":[{"name":"alectinib","slug":"alectinib","company":"Hoffman-La Roche"},{"name":"brigatinib","slug":"brigatinib","company":"Ariad"},{"name":"ceritinib","slug":"ceritinib","company":"Novartis Pharms Corp"},{"name":"crizotinib","slug":"crizotinib","company":"Pf Prism Cv"}],"globalPrevalence":2200000},{"indication":"Small cell carcinoma of lung","otherDrugs":[{"name":"doxorubicin","slug":"doxorubicin","company":""},{"name":"etoposide","slug":"etoposide","company":""},{"name":"etoposide phosphate","slug":"etoposide-phosphate","company":"Bristol Myers Squibb"},{"name":"lurbinectedin","slug":"lurbinectedin","company":"Jazz"}],"globalPrevalence":null},{"indication":"Transitional cell carcinoma","otherDrugs":[{"name":"atezolizumab","slug":"atezolizumab","company":"Genentech Inc"},{"name":"nivolumab","slug":"nivolumab","company":"Bristol Myers Squibb"}],"globalPrevalence":null}],"mechanism":{"target":"Programmed cell death 1 ligand 1","novelty":"Follow-on","targets":[{"gene":"CD274","source":"DrugCentral","target":"Programmed cell death 1 ligand 1","protein":"Programmed cell death 1 ligand 1","isPrimary":true,"activityType":"","activityValue":null}],"moaClass":"Programmed Death Ligand-1 Antagonists","modality":"Monoclonal Antibody","drugClass":"Programmed Death Ligand-1 Blocker [EPC]","explanation":"Expression of programmed cell death ligand-1 (PD-L1) can be induced by inflammatory signals (e.g., IFN-gamma) and can be expressed on both tumor cells and tumor-associated immune cells in the tumor microenvironment. PD-L1 blocks T-cell function and activation through interaction with PD-1 and CD80 (B7.1). By binding to its receptors, PD-L1 reduces cytotoxic T-cell activity, proliferation, and cytokine production.Durvalumab is human immunoglobulin G1 kappa (IgG1) monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80 (B7.1). Blockade of PD-L1/PD-1 and PD-L1/CD80 interactions releases the inhibition of immune responses, without inducing antibody dependent cell-mediated cytotoxicity (ADCC).PD-L1 blockade with durvalumab led to increased T-cell activation in vitro and decreased tumor size in co-engrafted human tumor and immune cell xenograft mouse models.","oneSentence":"Imfinzi works by blocking the PD-L1 protein, allowing the immune system to recognize and attack cancer cells.","technicalDetail":"Imfinzi is a monoclonal antibody that binds to the PD-L1 protein, preventing its interaction with the PD-1 receptor on T-cells, thereby releasing the brakes on the immune system and allowing it to attack cancer cells."},"_wikipedia":{"url":"https://en.wikipedia.org/wiki/Durvalumab","title":"Durvalumab","extract":"Durvalumab, sold under the brand name Imfinzi, is an anti-cancer medication used for treatment of various types of cancer. It was developed by Medimmune/AstraZeneca. It is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that binds to programmed cell death ligand 1 (PD-L1) on cancer cells and blocks interactions with PD-1 and CD80 (B7.1) on T cells.","wiki_history":"== History ==\n=== Clinical trials ===\nthumb|Immunotherapy: mechanism of action for Durvalumab, Pembrolizumab, Ipilimumab, Atezolizumab.\nA phase Ib clinical trial of durvalumab and tremelimumab showed some activity in non-small cell lung cancer (NSCLC) Phase I data in advanced metastatic urothelial bladder (Study 1108) has led to FDA breakthrough therapy designation. Early results of a phase I trial combining durvalumab and gefitinib in participants with lung cancer \"showed promise\". A phase I clinical trial is currently underway using durvalumab with a TLR 7/8 agonist (MEDI 9197) for solid tumors. A phase 1b/2a trial is underway combining durvalumab with an HPV DNA vaccine (MEDI 0457) in participants with HPV-associated recurrent/metastatic head and neck cancer.\n\n==== MYSTIC ====\nIn July 2017, AstraZeneca announced that a phase III trial of durvalumab with tremelimumab as a first-line treatment of non-small cell lung cancer failed to meet its primary endpoint of progression-free survival.\n\n==== PACIFIC ====\nIn November 2017, the double-blinded phase III AstraZeneca PACIFIC clinical trial demonstrated the efficacy of durvalumab in the treatment of stage III non-small cell lung cancer. 709 participants with stage III NSCLC who did not have disease progression after two or more cycles of a platinum-based chemotherapy were randomly assigned to receive durvalumab or a placebo as consolidation therapy for their lung cancer. Durvalumab increased the median progression-free survival from 5.6 months (placebo) to 16.8 months (durvalumab); the 12 month progression-free survival rate was increased from 35.3% (placebo) to 55.9% (durvalumab), and the 18 month progression-free survival rate was increased from 27.0% (placebo) to 44.2% (durvalumab).\n\n==== CASPIAN ====\nIn March 2021, the open-label, sponsor-blind (AstraZeneca), randomised, controlled phase III trial at 209 cancer treatment centres in 23 countries worldwide (CASPIAN) demonstrated the efficacy of durvalumab in combinat"},"commercial":{"launchDate":"2017","revenueYear":2024,"_launchSource":"DrugCentral (FDA 2017-05-01, ASTRAZENECA UK LTD)","annualRevenue":4900,"revenueSource":"Verified: AstraZeneca AR","revenueCurrency":"USD","revenueConfidence":"verified"},"references":[{"id":1,"url":"https://drugcentral.org/drugcard/5234","fields":["approvals","synonyms","ATC","PK","indications","contraindications","DDIs","targets","patents","FAERS"],"source":"DrugCentral"},{"id":2,"url":"https://clinicaltrials.gov/search?intr=durvalumab","fields":["trials"],"source":"ClinicalTrials.gov"},{"id":3,"url":"https://pubmed.ncbi.nlm.nih.gov/?term=durvalumab","fields":["publications"],"source":"PubMed/NCBI"},{"id":4,"url":"https://en.wikipedia.org/wiki/Durvalumab","fields":["history","overview"],"source":"Wikipedia"}],"_emaChecked":true,"_enrichedAt":"2026-03-30T02:31:36.111018","_validation":{"fieldsValidated":0,"lastValidatedAt":"2026-04-19T23:44:35.328698+00:00","fieldsConflicting":7,"overallConfidence":0.8},"biosimilars":[],"competitors":[{"drugName":"nivolumab","drugSlug":"nivolumab","fdaApproval":"2014-12-22","relationship":"same-class"},{"drugName":"pembrolizumab","drugSlug":"pembrolizumab","fdaApproval":"2014-09-04","relationship":"same-class"},{"drugName":"avelumab","drugSlug":"avelumab","fdaApproval":"2017-03-23","relationship":"same-class"},{"drugName":"atezolizumab","drugSlug":"atezolizumab","fdaApproval":"2016-05-18","relationship":"same-class"},{"drugName":"cemiplimab","drugSlug":"cemiplimab","fdaApproval":"2018-09-28","relationship":"same-class"},{"drugName":"dostarlimab","drugSlug":"dostarlimab","fdaApproval":"2021-04-22","relationship":"same-class"},{"drugName":"retifanlimab","drugSlug":"retifanlimab","fdaApproval":"2023-03-22","relationship":"same-class"}],"genericName":"durvalumab","indications":{"approved":[{"name":"Extensive stage primary small cell carcinoma of lung","source":"DrugCentral","snomedId":"","regulator":"FDA","eligibility":"Adult patients with extensive-stage small cell lung cancer, first-line treatment in combination with etoposide and either carboplatin or cisplatin."},{"name":"Liver cell carcinoma","source":"DrugCentral","snomedId":109841003,"regulator":"FDA","eligibility":"Not specified"},{"name":"Metastatic carcinoma to biliary tract","source":"DrugCentral","snomedId":"","regulator":"FDA","eligibility":"Not specified"},{"name":"Non-small cell lung cancer","source":"DrugCentral","snomedId":254637007,"regulator":"FDA","eligibility":"Adult patients with unresectable, Stage III non-small cell lung cancer whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.","usPrevalence":236000,"globalPrevalence":2200000,"prevalenceMethod":"curated","prevalenceSource":"IARC GLOBOCAN, 2022"},{"name":"Small cell carcinoma of lung","source":"DrugCentral","snomedId":254632001,"regulator":"FDA"},{"name":"Transitional cell carcinoma","source":"DrugCentral","snomedId":27090000,"regulator":"FDA","eligibility":"Not specified"}],"offLabel":[],"pipeline":[]},"_fixedFields":["primaryTarget"],"drugCategory":"active","labelChanges":[],"relatedDrugs":[{"drugId":"nivolumab","brandName":"nivolumab","genericName":"nivolumab","approvalYear":"2014","relationship":"same-class"},{"drugId":"pembrolizumab","brandName":"pembrolizumab","genericName":"pembrolizumab","approvalYear":"2014","relationship":"same-class"},{"drugId":"avelumab","brandName":"avelumab","genericName":"avelumab","approvalYear":"2017","relationship":"same-class"},{"drugId":"atezolizumab","brandName":"atezolizumab","genericName":"atezolizumab","approvalYear":"2016","relationship":"same-class"},{"drugId":"cemiplimab","brandName":"cemiplimab","genericName":"cemiplimab","approvalYear":"2018","relationship":"same-class"},{"drugId":"dostarlimab","brandName":"dostarlimab","genericName":"dostarlimab","approvalYear":"2021","relationship":"same-class"},{"drugId":"retifanlimab","brandName":"retifanlimab","genericName":"retifanlimab","approvalYear":"2023","relationship":"same-class"}],"trialDetails":[{"nctId":"NCT02125461","phase":"PHASE3","title":"A 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