{"id":"tremelimumab","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":"41876974","year":"2026","title":"The effect of prior transarterial chemoembolization on response to immune checkpoint inhibitor treatment in patients with hepatocellular carcinoma.","finding":"","journal":"Clinical and molecular hepatology","studyType":"Clinical Study"},{"pmid":"41870699","year":"2026","title":"A case of a patient with advanced HCC with Vp4 on hemodialysis who responded to a multimodality treatment including hepatic arterial infusion, radiation therapy, immunotherapy, and molecular-targeted drugs.","finding":"","journal":"Clinical journal of gastroenterology","studyType":"Clinical Study"},{"pmid":"41850829","year":"2026","title":"Favorable Response to Chemotherapy with Durvalumab plus Tremelimumab in Two Cases of KRAS G12C-Positive Pulmonary Sarcomatoid Carcinoma: A Case Report.","finding":"","journal":"Internal medicine (Tokyo, Japan)","studyType":"Clinical Study"},{"pmid":"41814915","year":"2026","title":"Impact of Borderline Resectable Criteria on Hepatocellular Carcinoma Treatment From the Perspective of Tumor Burden.","finding":"","journal":"World journal of surgery","studyType":"Clinical Study"}],"_fda":{"id":"390ff583-8e40-4690-ac4c-b4eaef2229d2","set_id":"6690679c-be2f-4588-a2e4-89fff74dd6be","openfda":{"nui":["N0000182635","N0000182634","N0000182157"],"unii":["QEN1X95CIX"],"route":["INTRAVENOUS"],"rxcui":["2619317","2619323","2619325","2619326"],"spl_id":["390ff583-8e40-4690-ac4c-b4eaef2229d2"],"brand_name":["IMJUDO"],"spl_set_id":["6690679c-be2f-4588-a2e4-89fff74dd6be"],"package_ndc":["0310-4505-25","0310-4535-30"],"product_ndc":["0310-4505","0310-4535"],"generic_name":["TREMELIMUMAB"],"product_type":["HUMAN PRESCRIPTION DRUG"],"pharm_class_pe":["Increased T Lymphocyte Activation [PE]"],"substance_name":["TREMELIMUMAB"],"pharm_class_epc":["CTLA-4-directed Blocking Antibody [EPC]"],"pharm_class_moa":["CTLA-4-directed Antibody Interactions [MoA]"],"manufacturer_name":["AstraZeneca Pharmaceuticals LP"],"application_number":["BLA761289"],"is_original_packager":[true]},"version":"14","pregnancy":["8.1 Pregnancy Risk summary Based on findings from animal studies and its mechanism of action, IMJUDO can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of IMJUDO in pregnant women. In animal studies, CTLA-4 blockade is associated with increased risk of immune-mediated rejection of the developing fetus and fetal death ( see Data ). Human immunoglobulin G2 (IgG2) is known to cross the placental barrier; therefore, IMJUDO has the potential to be transmitted from the mother to the developing fetus. Advise pregnant women and females of reproductive potential 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 In a reproduction study, administration of tremelimumab-actl to pregnant cynomolgus monkeys during the period of organogenesis was not associated with maternal toxicity or effects on embryo-fetal development at exposure levels approximately 4 to 31-times higher than those observed at a recommended dose range of 75 mg to 300 mg based on area under the curve (AUC). CTLA-4 plays a role in maintaining maternal immune tolerance to the fetus to preserve pregnancy and in immune regulation of the newborn. In a murine model of pregnancy, CTLA-4 blockade resulted in increased resorptions and reduced live fetuses. Mated genetically engineered mice heterozygous for CTLA-4 (CTLA-4+/-) gave birth to CTLA-4+/- offspring and offspring deficient in CTLA-4 (homozygous negative, CTLA-4-/-) that appeared healthy at birth. The CTLA-4-/- homozygous negative offspring developed signs of a lymphoproliferative disorder and died by 3 to 4 weeks of age with multiorgan tissue destruction. Based on its mechanism of action, fetal exposure to tremelimumab-actl may increase the risk of developing immune-mediated disorders or altering the normal immune response."],"description":["11 DESCRIPTION Tremelimumab-actl, a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blocking human IgG2 monoclonal antibody, is produced by recombinant DNA technology in NS0 cell suspension culture and has a molecular weight of 149 kDa. IMJUDO (tremelimumab-actl) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution, in a single-dose vial for intravenous infusion after dilution. IMJUDO contains tremelimumab-actl at a concentration of 20 mg/mL in either a 25 mg/1.25 mL or a 300 mg/15 mL single-dose vial. Each mL contains 20 mg of tremelimumab-actl, and edetate disodium (0.09 mg), histidine (0.68 mg), L‑histidine hydrochloride monohydrate (3.3 mg), polysorbate 80 (0.2 mg), trehalose (76 mg), and Water for Injection, USP. The pH is approximately 5.5."],"how_supplied":["16 HOW SUPPLIED/STORAGE AND HANDLING IMJUDO (tremelimumab-actl) injection is a clear to slightly opalescent, colorless to slightly yellow solution supplied in a carton containing one single-dose vial in the following concentrations: • 25 mg/1.25 mL (20 mg/mL) (NDC 0310-4505-25) • 300 mg/15 mL (20 mg/mL) (NDC 0310-4535-30) 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."],"spl_medguide":["MEDICATION GUIDE IMJUDO ® (im-JEW-doh) (tremelimumab-actl) injection What is the most important information I should know about IMJUDO? IMJUDO is a medicine that may treat certain cancers by working with your immune system. IMJUDO in combination with durvalumab 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 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 IMJUDO. 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 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 IMJUDO. 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 IMJUDO, if you have severe side effects. What is IMJUDO? IMJUDO is a prescription medicine used to treat adults with: • a type of liver cancer called unresectable hepatocellular carcinoma (uHCC). IMJUDO may be used in combination with durvalumab when your uHCC cannot be removed by surgery. • a type of lung cancer called non-small cell lung cancer (NSCLC). IMJUDO may be used in combination with durvalumab and chemotherapy that contains platinum when your NSCLC: o has spread to other part of your body (metastatic), and o your tumor does not have an abnormal “EGFR” or “ALK” gene. It is not known if IMJUDO is safe and effective in children. Before you receive IMJUDO, 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 a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome • are pregnant or plan to become pregnant. IMJUDO can harm your unborn baby. Females who are able to become pregnant o Your healthcare provider should do a pregnancy test before you start treatment with IMJUDO. o You should use an effective method of birth control during your treatment and for 3 months after your last dose of IMJUDO. Talk to your healthcare provider about birth control methods that you can use during this time. o Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with IMJUDO. • are breastfeeding or plan to breastfeed. It is not known if IMJUDO passes into your breast milk. Do not breastfeed during treatment and for 3 months after your last dose of IMJUDO. 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 IMJUDO? • Your healthcare provider will determine your treatment schedule and cycles of treatment. • Your healthcare provider will give you IMJUDO into your vein through an intravenous (IV) line over 60 minutes. • For the treatment of uHCC: o On the same day you receive IMJUDO, you will receive durvalumab through an intravenous (IV) line over 60 minutes. o IMJUDO is given to you as a single dose. o You will then receive durvalumab every 4 weeks • For the treatment of NSCLC: o On the same day you receive IMJUDO, you will receive durvalumab followed by platinum-containing chemotherapy. You will receive combination chemotherapy every 3 weeks for four cycles (Cycle 1 to 4). o You will then receive durvalumab for one cycle (Cycle 5), and then IMJUDO in combination with durvalumab for one cycle only (Cycle 6). o You will then receive durvalumab every 4 weeks. o Your healthcare provider will decide if you will also receive additional chemotherapy with each cycle. • Your healthcare provider will test your blood to check you for certain side effects. • If you miss your appointment, call your healthcare provider as soon as possible to reschedule your appointment. What are the possible side effects of IMJUDO? IMJUDO can cause serious side effects, including: See “What is the most important information I should know about IMJUDO?” The most common side effects of IMJUDO when used in combination with durvalumab in adults with uHCC include: • rash • diarrhea • feeling tired • itchiness • muscle or bone pain • stomach area (abdominal) pain The most common side effects of IMJUDO when used in combination with durvalumab and platinum-containing chemotherapy in adults with metastatic NSCLC include: • nausea • feeling tired or weak • muscle or bone pain • decreased appetite • rash • diarrhea Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of IMJUDO. 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 IMJUDO. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. If you would like more information about IMJUDO, talk with your healthcare provider. You can ask your healthcare provider for information about IMJUDO that is written for health professionals. What are the ingredients in IMJUDO? Active ingredient: tremelimumab-actl Inactive ingredients: edetate disodium, histidine, L-histidine hydrochloride monohydrate, polysorbate 80, trehalose, and Water for Injection, USP. Manufactured for: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850 Manufactured by: AstraZeneca AB, Södertälje, Sweden SE-15185 US License No. 2059 IMJUDO ® is a registered trademark of AstraZeneca group of companies. For more information, call 1-800-236-9933 or go to www.IMJUDO.com © AstraZeneca 2024 This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 01/2024"],"geriatric_use":["8.5 Geriatric Use Of the 393 patients with uHCC treated with IMJUDO in combination with durvalumab, 50% of patients were 65 years or older and 13% of patients were 75 years or older. No overall differences in safety or efficacy of IMJUDO have been observed between patients 65 years or older and younger adult patients. Of the 330 patients with metastatic NSCLC treated with IMJUDO in combination with durvalumab and platinum-based chemotherapy, 143 (43%) patients were 65 years or older and 35 (11%) patients were 75 years or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects."],"pediatric_use":["8.4 Pediatric Use The safety and effectiveness of IMJUDO have not been established in pediatric patients. Safety and efficacy were assessed but not established in a multi-center, open-label study (NCT03837899) in which 41 pediatric patients aged 1 to < 17 years with advanced solid tumors received IMJUDO in combination with durvalumab. No new safety signals were observed in pediatric patients in this study. Tremelimumab-actl systemic exposure in pediatric patients ≥ 35 kg was within the range of the values previously observed in adults given the same weight-based dose, whereas the systemic exposure in pediatric patients < 35 kg was lower than that of adults."],"effective_time":"20240724","clinical_studies":["14 CLINICAL STUDIES 14.1 Hepatocellular Carcinoma (HCC) Unresectable HCC - HIMALAYA The efficacy of IMJUDO in combination with durvalumab 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 (IMJUDO plus durvalumab or durvalumab) or sorafenib. Study treatment consisted of IMJUDO as a one-time single intravenous infusion of 300 mg in combination with durvalumab 1,500 mg on the same day, followed by durvalumab every 4 weeks; durvalumab 1,500 mg every 4 weeks; or sorafenib 400 mg given orally twice daily, until disease progression or unacceptable toxicity. The efficacy assessment of IMJUDO is based on patients randomized to the IMJUDO plus durvalumab 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 a 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 was deriving clinical benefit as determined by the investigator. The major efficacy outcome measure was overall survival (OS) between the IMJUDO plus durvalumab 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 IMJUDO plus durvalumab 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%), uninfected (42%). Efficacy results are presented in Table 9 and Figure 1. Table 9. Efficacy Results for HIMALAYA Study Endpoint IMJUDO and Durvalumab (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 (IMJUDO and durvalumab 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 IMJUDO and durvalumab vs. sorafenib was 0.0398 (Lan and DeMets 1983). 0.0035 PFS Number of events (%) 335 (85.2) 327 (84.1) Median PFS (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 1. Kaplan-Meier curve of OS Figure 1 14.2 Metastatic NSCLC Metastatic NSCLC – POSEIDON The efficacy of IMJUDO in combination with durvalumab 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 trial (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 IMJUDO in combination with durvalumab and platinum-based chemotherapy according to the regimens listed below, durvalumab 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: • IMJUDO 75 mg (or 1mg/kg for patients < 30kg) with durvalumab 1,500 mg and platinum-based chemotherapy every 3 weeks for 4 cycles, followed by durvalumab 1,500 mg every 4 weeks as a single agent. A fifth dose of IMJUDO 75 mg (or 1mg/kg for patients < 30kg) was given at Week 16 in combination with durvalumab 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 IMJUDO and durvalumab in combination 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 IMJUDO was given up to a maximum of 5 doses. Durvalumab and histology-based pemetrexed continued every 4 weeks until disease progression or unacceptable toxicity. Administration of durvalumab 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 durvalumab monotherapy were given the option to be retreated with 4 additional cycles of IMJUDO in combination with durvalumab. 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 IMJUDO and durvalumab 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 IMJUDO with durvalumab 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 10 and Figure 2. Table 10. Efficacy Results for POSEIDON IMJUDO with durvalumab 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 intervals. 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 2. Kaplan-Meier curves of OS in POSEIDON Figure 2 figure_2_data"],"pharmacokinetics":["12.3 Pharmacokinetics The pharmacokinetics of tremelimumab-actl was studied in patients with other solid tumors following administration of doses 1 mg/kg, 3 mg/kg, and 10 mg/kg (1- to 10-times the approved recommended dosage) administered once every 4 weeks for 4 doses. The pharmacokinetics of tremelimumab-actl as a single dose of 300 mg were evaluated in patients with HCC. The AUC of tremelimumab-actl increased proportionally from 1 mg/kg to 10 mg/kg every 4 weeks (1 to 10-times the approved recommended dosage) and steady state was achieved at approximately 12 weeks. Distribution The geometric mean (% coefficient of variation [CV%]) of tremelimumab-actl for central (V1) and peripheral (V2) volume of distribution was 3.45 (24%) and 2.66 (34%) L, respectively. Elimination The geometric mean (CV%) terminal half-life of tremelimumab-actl was 16.9 days (19%) after a single dose and 18.2 days (19%) during steady state. The geometric mean (CV%) clearance of tremelimumab-actl was 0.286 L/day (32%) after a single dose and 0.263 L/day (32%) during steady state. Specific Populations There were no clinically significant differences in the pharmacokinetics of tremelimumab-actl based on body weight (34 to149 kg), age (18 to 87 years), sex, race (White, Black, Asian, Native Hawaiian, Pacific Islander, or American Indian), serum albumin levels (0.3 to 396 g/L), lactate dehydrogenase levels (12 to 5570 U/L), soluble PD-L1 (67 to 349 pg/mL), tumor type (NSCLC, HCC), organ dysfunction including mild to moderate renal impairment (CLcr 30 to 89 mL/min), and mild to moderate hepatic impairment (bilirubin < 3 x ULN and any AST). The effect of severe renal impairment (CLcr 15 to 29 mL/min) or severe hepatic impairment (bilirubin > 3 x ULN and any AST) on the pharmacokinetics of tremelimumab-actl 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) ]. Most common adverse reactions (≥ 20%) of patients with uHCC are rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain. Most common laboratory abnormalities (≥ 40%) of patients with uHCC are AST increased, ALT increased, hemoglobin decreased, sodium decreased, bilirubin increased, alkaline phosphatase increased, and lymphocytes decreased. ( 6.1 ) Most common adverse reactions (≥ 20%) of patients with metastatic NSCLC were nausea, fatigue, musculoskeletal pain, decreased appetite, rash, and diarrhea. ( 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 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 reflect exposure to IMJUDO 300 mg in combination with durvalumab 1,500 mg in 388 patients in HIMALAYA. In the HIMALAYA study patients received IMJUDO 300 mg administered as a single intravenous infusion in combination with durvalumab 1,500 mg on the same day, followed by durvalumab every 4 weeks. The data also reflects exposure to IMJUDO 75 mg in combination with durvalumab 1,500 mg and histology-based platinum chemotherapy regimens in the pooled safety population (N=596) of 330 patients in POSEIDON [see Clinical Studies (14.1) ] , and 266 patients in CASPIAN who received up to four cycles of platinum-etoposide plus durvalumab 1,500 mg with tremelimumab-actl 75 mg every 3 weeks, followed by durvalumab 1,500 mg every 4 weeks (an unapproved regimen for extensive-stage small cell lung cancer). Of these patients, 64% received the maximum of 5 doses of IMJUDO and 79% received at least 4 doses. In this pooled safety population, the most common (> 20%) adverse reactions were nausea (37%), decreased appetite (25%), and fatigue (22%). In this pooled safety population, the most common Grade 3 or 4 (> 10%) laboratory abnormalities were neutropenia (39%), leukopenia (21%), lymphocytopenia (20%), anemia (20%), hyponatremia (14%), lipase increased (12%), and thrombocytopenia (11%). The data described in this section reflect exposure to IMJUDO in patients with uHCC included in the HIMALAYA study and in patients with metastatic NSCLC enrolled in the POSEIDON study. Hepatocellular Carcinoma Unresectable HCC - HIMALAYA The safety of IMJUDO administered in combination with durvalumab 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 IMJUDO 300 mg administered as a single intravenous infusion in combination with durvalumab 1,500 mg on the same day, followed by durvalumab every 4 weeks or sorafenib 400 mg given orally twice daily. Serious adverse reactions occurred in 41% of patients who received IMJUDO in combination with durvalumab. 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 IMJUDO in combination with durvalumab, 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 the 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 5 summarizes the adverse reactions that occurred in patients treated with IMJUDO in combination with durvalumab in the HIMALAYA study. Table 5. Adverse Reactions Occurring in ≥ 10% Patients in the HIMALAYA study IMJUDO and Durvalumab (N=388) Sorafenib (N=374) Adverse Reaction All Grades (%) Grade 3-4 (%) All Grades (%) Grade 3-4 (%) Gastrointestinal disorders Diarrhea Represents a composite of multiple related terms. 27 6 45 4.3 Abdominal pain 20 1.8 24 4 Nausea 12 0 14 0 Skin and subcutaneous tissue disorders Rash 32 2.8 57 12 Pruritus 23 0 6 0.3 Metabolism and nutrition disorders Decreased appetite 17 1.3 18 0.8 General disorders and administration site conditions Fatigue 26 3.9 30 6 Pyrexia 13 0.3 9 0.3 Psychiatric disorders Insomnia 10 0.3 4.3 0 Endocrine disorders Hypothyroidism 14 0 6 0 Musculoskeletal and Connective Tissue Disorders Musculoskeletal pain 22 2.6 17 0.8 Table 6 summarizes the laboratory abnormalities that occurred in patients treated with IMJUDO in combination with durvalumab in the HIMALAYA study. Table 6. Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20% of Patients in the HIMALAYA study IMJUDO and Durvalumab Sorafenib Laboratory Abnormality Any grade (%) 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 Non-Small Cell Lung Cancer Metastatic NSCLC – POSEIDON The safety of IMJUDO in combination with durvalumab and platinum-based chemotherapy in patients with metastatic NSCLC was evaluated in POSEIDON (NCT03164616), a randomized, open-label, multicenter, active-controlled trial. A total of 330 patients received IMJUDO (≥ 30 kg body weight received 75 mg and ≤ 30kg body weight received 1 mg/kg) in combination with durvalumab 1,500 mg and histology-based platinum chemotherapy regimens [see Clinical Studies (14.2) ] . Of these patients, 66% received up to the maximum 5 doses of IMJUDO and 79% received at least 4 doses. Treatment was continued with durvalumab as a single agent (or with durvalumab and histology-based pemetrexed for non-squamous patients, based on the investigator’s decision) until disease progression or unacceptable toxicity. The trial excluded patients with active or prior autoimmune disease or with medical conditions that required systemic corticosteroids or immunosuppressants [see Clinical Studies (14.2) ] . The median age of patients who received IMJUDO in combination with durvalumab 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 IMJUDO in combination with durvalumab 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 IMJUDO in combination with durvalumab 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 (1 patient), dyspnea (1 patient), sudden death (1 patient), and ischemic stroke (1 patient). Permanent discontinuation of IMJUDO or durvalumab due to an adverse reaction occurred in 17% of the patients. Adverse reactions which resulted in permanent discontinuation of IMJUDO or durvalumab in > 2% of patients included pneumonia. Dosage interruptions or delay of IMJUDO and durvalumab due to an adverse reaction occurred in 41% of patients. Adverse reactions which required dosage interruption or delay of IMJUDO and durvalumab 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 7 summarizes the adverse reactions in POSEIDON. Table 7. Adverse Reactions (≥ 10%) in Patients with NSCLC Who Received IMJUDO in the POSEIDON Study IMJUDO with durvalumab 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 (%) Respiratory, thoracic and mediastinal disorders Cough/Productive Cough Includes cough and productive cough. 12 0 8 0.3 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 Endocrine disorders Hypothyroidism Includes blood thyroid stimulating hormone increased and hypothyroidism. 13 0 2.1 0 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 Alopecia 10 0 6 0 Pruritus 11 0 4.5 0 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, spinal pain. 29 0.6 22 1.5 Metabolism and nutrition disorders Decreased appetite 28 1.5 25 1.2 Infections and Infestations Pneumonia Includes lower respiratory tract infection, pneumocystis jirovecii pneumonia, pneumonia, pneumonia aspiration, 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 Nervous system disorders Headache Includes headache, migraine. 11 0 8 0.6 Table 8 summarizes the laboratory abnormalities in POSEIDON. Table 8: Select Laboratory Abnormalities (≥ 10%) That Worsened from Baseline in Patients with NSCLC Who Received IMJUDO in the POSEIDON Study Laboratory Abnormality IMJUDO with Durvalumab and Platinum-based chemotherapy Platinum-based chemotherapy All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Chemistry Lipase increased 35 14 25 5 Hyponatremia 55 13 50 11 Hypernatremia 15 0 14 0 Amylase increased 41 9 25 6 Hypokalemia 21 7 17 2.8 Hyperglycemia 42 6 37 3.1 Increased ALT 64 6 56 4.7 Increased AST 63 5 55 2.2 Blood creatinine increased 89 4.0 83 1.9 Increased Alkaline Phosphatase 33 3.4 26 1.2 Gamma Glutamyl Transferase increased 38 2.2 35 4.7 Hyperkalemia 49 2.2 35 2.8 Albumin decreased 27 1.9 18 0.9 Hypocalcemia 58 0.9 49 0.9 Hypomagnesemia 12 4 23 0 Bilirubinemia 16 0.9 8 0.3 Hematology Neutropenia 71 37 69 32 Anemia 84 24 84 25 Leukopenia 77 21 81 18 Lymphocytopenia 67 20 60 19 Thrombocytopenia 53 11 54 12"],"contraindications":["4 CONTRAINDICATIONS None. None. ( 4 )"],"spl_medguide_table":["<table width=\"100%\"><col width=\"47%\"/><col width=\"30%\"/><col width=\"22%\"/><tbody><tr><td align=\"center\" colspan=\"3\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">MEDICATION GUIDE</content> IMJUDO<sup>&#xAE;</sup> (im-JEW-doh)</paragraph><paragraph>(tremelimumab-actl)</paragraph><paragraph>injection</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">What is the most important information I should know about IMJUDO?</content></paragraph><paragraph>IMJUDO is a medicine that may treat certain cancers by working with your immune system.</paragraph><paragraph>IMJUDO in combination with durvalumab 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><paragraph><content styleCode=\"bold\">Lung problems.</content></paragraph></td></tr><tr><td styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption> </caption><list listType=\"unordered\"><item><caption>&#x2022;</caption>cough</item></list></item></list></td><td valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>shortness of breath</item></list></td><td styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>chest pain</item></list></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Intestinal problems.</content></paragraph></td></tr><tr><td styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>diarrhea (loose stools) or more frequent bowel movements than usual</item><item><caption>&#x2022;</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>&#x2022;</caption>severe stomach-area (abdomen) pain or tenderness</item></list></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Liver problems.</content></paragraph></td></tr><tr><td styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>yellowing of your skin or the whites of your eyes</item><item><caption>&#x2022;</caption>severe nausea or vomiting</item><item><caption>&#x2022;</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>&#x2022;</caption>dark urine (tea colored)</item><item><caption>&#x2022;</caption>bleeding or bruising more easily than normal</item></list></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Hormone gland problems.</content></paragraph></td></tr><tr><td styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>headaches that will not go away or unusual headaches</item><item><caption>&#x2022;</caption>eye sensitivity to light</item><item><caption>&#x2022;</caption>eye problems</item><item><caption>&#x2022;</caption>rapid heartbeat</item><item><caption>&#x2022;</caption>increase sweating</item><item><caption>&#x2022;</caption>extreme tiredness</item><item><caption>&#x2022;</caption>weight gain or weight loss</item><item><caption>&#x2022;</caption>feeling more hungry or thirsty than usual</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>urinating more often than usual</item><item><caption>&#x2022;</caption>hair loss</item><item><caption>&#x2022;</caption>feeling cold</item><item><caption>&#x2022;</caption>constipation</item><item><caption>&#x2022;</caption>your voice gets deeper</item><item><caption>&#x2022;</caption>dizziness or fainting</item><item><caption>&#x2022;</caption>changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness</item></list></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Kidney problems.</content></paragraph></td></tr><tr><td styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>decrease in your amount of urine</item><item><caption>&#x2022;</caption>blood in your urine</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>swelling of your ankles</item><item><caption>&#x2022;</caption>loss of appetite</item></list></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Skin problems.</content></paragraph></td></tr><tr><td styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>rash</item><item><caption>&#x2022;</caption>itching</item><item><caption>&#x2022;</caption>skin blistering or peeling</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>painful sores or ulcers in mouth or nose, throat, or genital area</item><item><caption>&#x2022;</caption>fever or flu-like symptoms</item><item><caption>&#x2022;</caption>swollen lymph nodes</item></list></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Pancreas problems.</content></paragraph></td></tr><tr><td styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>pain in your upper stomach-area (abdomen)</item><item><caption>&#x2022;</caption>severe nausea or vomiting</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>loss of appetite</item></list></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><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 IMJUDO. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include:</content></paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption>chest pain, irregular heartbeats, shortness of breath or swelling of ankles</item><item><caption>&#x2022;</caption>confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems</item><item><caption>&#x2022;</caption>tingling, numbness or weakness of the arms or legs</item><item><caption>&#x2022;</caption>double vision, blurry vision, sensitivity to light, eye pain, changes in eye sight</item><item><caption>&#x2022;</caption>persistent or severe muscle pain or weakness, muscle cramps, joint pain, joint stiffness or swelling</item><item><caption>&#x2022;</caption>low red blood cells, bruising</item></list></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Infusion reactions that can sometimes be severe or life-threatening</content>. Signs and symptoms of infusion reactions may include:</paragraph></td></tr><tr><td styleCode=\"Lrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>chills or shaking</item><item><caption>&#x2022;</caption>itching or rash</item><item><caption>&#x2022;</caption>flushing</item><item><caption>&#x2022;</caption>shortness of breath or wheezing</item></list></td><td colspan=\"2\" styleCode=\"Rrule \" valign=\"top\"><list listType=\"unordered\"><item><caption>&#x2022;</caption>dizziness</item><item><caption>&#x2022;</caption>feel like passing out</item><item><caption>&#x2022;</caption>fever</item><item><caption>&#x2022;</caption>back or neck pain</item></list></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><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 IMJUDO. 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 IMJUDO, if you have severe side effects.</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">What is IMJUDO?</content></paragraph><paragraph>IMJUDO is a prescription medicine used to treat adults with:</paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">a type of liver cancer</content> called unresectable hepatocellular carcinoma (uHCC). IMJUDO may be used in combination with durvalumab when your uHCC cannot be removed by surgery.</item><item><caption>&#x2022;</caption><content styleCode=\"bold\">a type of lung cancer</content> called non-small cell lung cancer (NSCLC). IMJUDO may be used in combination with durvalumab and chemotherapy that contains platinum when your NSCLC:</item><item><caption>o</caption>has spread to other part of your body (metastatic), <content styleCode=\"bold\">and</content></item><item><caption>o</caption>your tumor does not have an abnormal &#x201C;EGFR&#x201D; or &#x201C;ALK&#x201D; gene.</item></list><paragraph>It is not known if IMJUDO is safe and effective in children.</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Before you receive IMJUDO, 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 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. IMJUDO 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>o</caption>Your healthcare provider should do a pregnancy test before you start treatment with IMJUDO.</item><item><caption>o</caption>You should use an effective method of birth control during your treatment and for 3 months after your last dose of IMJUDO. Talk to your healthcare provider about birth control methods that you can use during this time.</item><item><caption>o</caption>Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with IMJUDO.</item></list></item><item><caption>&#x2022;</caption>are breastfeeding or plan to breastfeed. It is not known if IMJUDO passes into your breast milk. Do not breastfeed during treatment and for 3 months after your last dose of IMJUDO.</item></list><paragraph><content styleCode=\"bold\">Tell your healthcare provider about all the medicines you take,</content> including prescription and over-the-counter medicines, vitamins, and herbal supplements.</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">How will I receive IMJUDO?</content></paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption>Your healthcare provider will determine your treatment schedule and cycles of treatment.</item><item><caption>&#x2022;</caption>Your healthcare provider will give you IMJUDO into your vein through an intravenous (IV) line over 60 minutes.</item><item><caption>&#x2022;</caption><content styleCode=\"bold\">For the treatment of uHCC:</content><list listType=\"unordered\"><item><caption>o</caption>On the same day you receive IMJUDO, you will receive durvalumab through an intravenous (IV) line over 60 minutes.</item><item><caption>o</caption>IMJUDO is given to you as a single dose.</item><item><caption>o</caption>You will then receive durvalumab every 4 weeks</item></list></item><item><caption>&#x2022;</caption><content styleCode=\"bold\">For the treatment of NSCLC:</content><list listType=\"unordered\"><item><caption>o</caption>On the same day you receive IMJUDO, you will receive durvalumab followed by platinum-containing chemotherapy. You will receive combination chemotherapy every 3 weeks for four cycles (Cycle 1 to 4).</item><item><caption>o</caption>You will then receive durvalumab for one cycle (Cycle 5), and then IMJUDO in combination with durvalumab for one cycle only (Cycle 6).</item><item><caption>o</caption>You will then receive durvalumab every 4 weeks.</item><item><caption>o</caption>Your healthcare provider will decide if you will also receive additional chemotherapy with each cycle.</item></list></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 your appointment, call your healthcare provider as soon as possible to reschedule your appointment.</item></list></td></tr><tr><td colspan=\"3\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">What are the possible side effects of IMJUDO?</content></paragraph><paragraph><content styleCode=\"bold\">IMJUDO can cause serious side effects, including:</content></paragraph><paragraph><content styleCode=\"bold\">See &#x201C;What is the most important information I should know about IMJUDO?&#x201D;</content></paragraph><paragraph>The most common side effects of IMJUDO when used in combination with durvalumab in adults with uHCC include:</paragraph></td></tr></tbody></table>","<table width=\"100%\"><col width=\"47%\"/><col width=\"53%\"/><tbody><tr><td 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 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 area (abdominal) pain</item></list></td></tr><tr><td colspan=\"2\" styleCode=\"Rrule Lrule \" valign=\"top\"><paragraph>The most common side effects of IMJUDO when used in combination with durvalumab and platinum-containing chemotherapy in adults with metastatic NSCLC include:</paragraph></td></tr><tr><td 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 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></tbody></table>","<table width=\"100%\"><col width=\"100%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule \" valign=\"top\"><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 the possible side effects of IMJUDO. 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 styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">General information about the safe and effective use of IMJUDO.</content></paragraph><paragraph>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. If you would like more information about IMJUDO, talk with your healthcare provider. You can ask your healthcare provider for information about IMJUDO that is written for health professionals.</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">What are the ingredients in IMJUDO?</content></paragraph><paragraph><content styleCode=\"bold\">Active ingredient: </content>tremelimumab-actl</paragraph><paragraph><content styleCode=\"bold\">Inactive ingredients: </content>edetate disodium, histidine, L-histidine hydrochloride monohydrate, polysorbate 80, trehalose, and Water for Injection, USP.</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule \" valign=\"top\"><paragraph>Manufactured for: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850</paragraph><paragraph>Manufactured by: AstraZeneca AB, S&#xF6;dert&#xE4;lje, Sweden SE-15185</paragraph><paragraph>US License No. 2059</paragraph><paragraph>IMJUDO<sup>&#xAE;</sup> is a registered trademark of AstraZeneca group of companies.</paragraph><paragraph>For more information, call 1-800-236-9933 or go to www.IMJUDO.com</paragraph><paragraph>&#xA9; AstraZeneca 2024</paragraph></td></tr></tbody></table>"],"mechanism_of_action":["12.1 Mechanism of Action CTLA-4 is a negative regulator of T-cell activity. Tremelimumab-actl is a monoclonal antibody that binds to CTLA-4 and blocks the interaction with its ligands CD80 and CD86, releasing CTLA-4-mediated inhibition of T-cell activation. In synergistic mouse tumor models, blocking CTLA-4 activity resulted in decreased tumor growth and increased proliferation of T cells in tumors."],"clinical_pharmacology":["12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action CTLA-4 is a negative regulator of T-cell activity. Tremelimumab-actl is a monoclonal antibody that binds to CTLA-4 and blocks the interaction with its ligands CD80 and CD86, releasing CTLA-4-mediated inhibition of T-cell activation. In synergistic mouse tumor models, blocking CTLA-4 activity resulted in decreased tumor growth and increased proliferation of T cells in tumors. 12.2 Pharmacodynamics The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of tremelimumab-actl have not been fully characterized. 12.3 Pharmacokinetics The pharmacokinetics of tremelimumab-actl was studied in patients with other solid tumors following administration of doses 1 mg/kg, 3 mg/kg, and 10 mg/kg (1- to 10-times the approved recommended dosage) administered once every 4 weeks for 4 doses. The pharmacokinetics of tremelimumab-actl as a single dose of 300 mg were evaluated in patients with HCC. The AUC of tremelimumab-actl increased proportionally from 1 mg/kg to 10 mg/kg every 4 weeks (1 to 10-times the approved recommended dosage) and steady state was achieved at approximately 12 weeks. Distribution The geometric mean (% coefficient of variation [CV%]) of tremelimumab-actl for central (V1) and peripheral (V2) volume of distribution was 3.45 (24%) and 2.66 (34%) L, respectively. Elimination The geometric mean (CV%) terminal half-life of tremelimumab-actl was 16.9 days (19%) after a single dose and 18.2 days (19%) during steady state. The geometric mean (CV%) clearance of tremelimumab-actl was 0.286 L/day (32%) after a single dose and 0.263 L/day (32%) during steady state. Specific Populations There were no clinically significant differences in the pharmacokinetics of tremelimumab-actl based on body weight (34 to149 kg), age (18 to 87 years), sex, race (White, Black, Asian, Native Hawaiian, Pacific Islander, or American Indian), serum albumin levels (0.3 to 396 g/L), lactate dehydrogenase levels (12 to 5570 U/L), soluble PD-L1 (67 to 349 pg/mL), tumor type (NSCLC, HCC), organ dysfunction including mild to moderate renal impairment (CLcr 30 to 89 mL/min), and mild to moderate hepatic impairment (bilirubin < 3 x ULN and any AST). The effect of severe renal impairment (CLcr 15 to 29 mL/min) or severe hepatic impairment (bilirubin > 3 x ULN and any AST) on the pharmacokinetics of tremelimumab-actl 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 comparisons of the incidence of ADA in the studies described below with the incidence of ADA in other studies, including those of tremelimumab-actl. In the HIMALAYA study, of the 182 patients who were treated with a single dose of tremelimumab-actl in combination with durvalumab once in every 4 weeks therapy and evaluable for the presence of ADAs against tremelimumab-actl at predose week 0 and week 4, 11% (20/182) of patients tested positive for anti-tremelimumab-actl antibodies. Among the 20 patients who tested positive for ADAs 40% (8/20) tested positive for neutralizing antibodies against tremelimumab-actl. There was no identified clinically significant effect of anti-tremelimumab-actl antibodies on the pharmacokinetics or safety of tremelimumab-actl; however, the effect of ADAs and neutralizing antibodies on the effectiveness of tremelimumab-actl is unknown. In the POSEIDON study, of the 278 ADA-evaluable patients who were treated with IMJUDO 75 mg for up to five doses in combination with durvalumab 1,500 mg and platinum-based chemotherapy every 3 weeks and evaluated for presence of ADAs against tremelimumab-actl at pre-dose week 0, week 3, and week 12, 14% (38/278) of patients tested positive for anti-tremelimumab-actl antibodies. Among the 38 patients who tested positive for ADAs, 82% (31/38) tested positive for neutralizing antibodies against tremelimumab-actl. There was no identified clinically significant effect of anti-tremelimumab-actl antibodies on pharmacokinetics or safety of tremelimumab-actl, however, the effect of ADAs on effectiveness of tremelimumab-actl is unknown."],"indications_and_usage":["1 INDICATIONS AND USAGE IMJUDO is a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blocking antibody indicated: • in combination with durvalumab, for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). ( 1.1 ) • in combination with durvalumab and platinum-based chemotherapy for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with no sensitizing epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations. ( 1.2 ) 1.1 Hepatocellular Carcinoma IMJUDO, in combination with durvalumab, is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). 1.2 Non-Small Cell Lung Cancer (NSCLC) IMJUDO, in combination with durvalumab and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) genomic tumor aberrations."],"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 nephritis with renal dysfunction, immune-mediated dermatologic adverse reactions and immune-mediated pancreatitis. o Monitor for early identification and management. Evaluate liver enzymes, creatinine, adrenocorticotropic hormone level and thyroid function at baseline and before each dose. o Withhold or permanently discontinue based on severity and type of reaction. • Infusion-Related Reactions: Interrupt, slow the rate of infusion, or permanently discontinue treatment based on the severity of the reaction. ( 5.2 ) • Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception. ( 5.3 , 8.1 , 8.3 ) 5.1 Severe and Fatal Immune-Mediated Adverse Reactions IMJUDO is a monoclonal antibody that blocks T-cell inhibitory signals induced by the CTLA-4 pathway, thereby removing inhibition of the immune response. In combination with durvalumab, a PD-L1 inhibitor, these drugs have the potential for induction of immune-mediated adverse reactions. Immune-mediated adverse reactions listed herein may not be inclusive of all possible severe and fatal immune-mediated reactions. 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 IMJUDO in combination with durvalumab. While immune-mediated adverse reactions usually manifest during treatment, immune-mediated adverse reactions can also manifest after discontinuation of IMJUDO and/or durvalumab. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of IMJUDO in combination with durvalumab. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and before each dose. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMJUDO and durvalumab depending on severity [see Dosage and Administration (2.2) ] . In general, if combination of IMJUDO and durvalumab requires interruption or discontinuation, administer systemic corticosteroid therapy (1 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 IMJUDO in combination with durvalumab can cause immune-mediated pneumonitis, which may be fatal. IMJUDO with Durvalumab Immune-mediated pneumonitis occurred in 1.3% (5/388) of patients receiving IMJUDO in combination with durvalumab, 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. IMJUDO with Durvalumab and Platinum-Based Chemotherapy Immune-mediated pneumonitis occurred in 3.5% (21/596) of patients receiving IMJUDO in combination with durvalumab 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 IMJUDO in combination with durvalumab and platinum-based chemotherapy can cause immune-mediated colitis, which may be fatal. IMJUDO in combination with durvalumab 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. IMJUDO with Durvalumab Immune-mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving IMJUDO in combination with durvalumab, 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 IMJUDO in combination with durvalumab. IMJUDO with Durvalumab and Platinum-Based Chemotherapy Immune-mediated colitis occurred in 6.5% (39/596) of patients receiving IMJUDO in combination with durvalumab and platinum-based chemotherapy, including fatal (0.2%) and Grade 3 (2.5%) adverse reactions. Events resolved in 33 of the 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 immunosuppressants. Intestinal perforation and large intestine perforation were reported in 0.1% of patients receiving IMJUDO in combination with durvalumab. Immune-Mediated Hepatitis IMJUDO in combination with durvalumab can cause immune-mediated hepatitis, which may be fatal. IMJUDO with Durvalumab Immune-mediated hepatitis occurred in 7.5% (29/388) of patients receiving IMJUDO in combination with durvalumab, 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. IMJUDO with Durvalumab and Platinum-Based Chemotherapy Immune-mediated hepatitis occurred in 3.9% (23/596) of patients receiving IMJUDO in combination with durvalumab and platinum-based chemotherapy, including fatal (0.3%), Grade 4 (0.5%), and Grade 3 (2%) adverse reactions. Events resolved in 12 of the 23 patients and resulted in permanent discontinuation in 27 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 : IMJUDO in combination with durvalumab 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 IMJUDO in combination with durvalumab based on the severity [see Dosage and Administration (2.2) ]. IMJUDO with Durvalumab Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMJUDO in combination with durvalumab, 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). IMJUDO with Durvalumab and Platinum-Based Chemotherapy Immune-mediated adrenal insufficiency occurred in 2.2% (13/596) of patients receiving IMJUDO in combination with durvalumab and platinum-based chemotherapy, 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: IMJUDO in combination with durvalumab 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 IMJUDO in combination with durvalumab depending on severity [see Dosage and Administration (2.2) ]. IMJUDO with Durvalumab Immune-mediated hypophysitis/hypopituitarism occurred in 1% (4/388) of patients receiving IMJUDO in combination with durvalumab. 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. IMJUDO with Durvalumab and Platinum-Based Chemotherapy Immune-mediated hypophysitis occurred in 1.3% (8/596) of patients receiving IMJUDO in combination with durvalumab and platinum-based chemotherapy, 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 : IMJUDO in combination with durvalumab 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 IMJUDO in combination with durvalumab based on the severity [see Dosage and Administration (2.2) ]. Thyroiditis: IMJUDO with Durvalumab Immune-mediated thyroiditis occurred in 1.5% (6/388) of patients receiving IMJUDO in combination with durvalumab. 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. IMJUDO with Durvalumab and Platinum-Based Chemotherapy Immune-mediated thyroiditis occurred in 1.2% (7/596) of patients receiving IMJUDO in combination with durvalumab and platinum-based chemotherapy. 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: IMJUDO with Durvalumab Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of patients receiving IMJUDO in combination with durvalumab, 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). IMJUDO with Durvalumab and Platinum-Based Chemotherapy Immune-mediated hyperthyroidism occurred in 5% (30/596) of patients receiving IMJUDO in combination with durvalumab and platinum-based chemotherapy, 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: IMJUDO with Durvalumab Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving IMJUDO in combination with durvalumab. 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). IMJUDO with Durvalumab and Platinum-Based Chemotherapy Immune-mediated hypothyroidism occurred in 8.6% (51/596) of patients receiving IMJUDO in combination with durvalumab and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions. Systemic corticosteroids were required in 2 patients (2/51) and all patients required endocrine therapy. 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 IMJUDO in combination with durvalumab based on the severity [see Dosage and Administration (2.2) ]. IMJUDO with Durvalumab Two patients (0.5%, 2/388) had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up. IMJUDO with Durvalumab and Platinum-Based Chemotherapy Immune-mediated Type 1 Diabetes Mellitus occurred in 0.5% (3/596) of patients receiving IMJUDO in combination with durvalumab and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions. All patients required endocrine therapy. Immune-Mediated Nephritis with Renal Dysfunction IMJUDO in combination with durvalumab can cause immune-mediated nephritis. IMJUDO with Durvalumab Immune-mediated nephritis occurred in 1% (4/388) of patients receiving IMJUDO in combination with durvalumab, 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). IMJUDO with Durvalumab and Platinum-Based Chemotherapy Immune-mediated nephritis occurred in 0.7% (4/596) of patients receiving IMJUDO in combination with durvalumab and platinum-based chemotherapy, 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 IMJUDO in combination with durvalumab 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 CTLA-4 and 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 IMJUDO in combination with durvalumab depending on severity [see Dosage and Administration (2.2) ]. IMJUDO with Durvalumab Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of patients receiving IMJUDO in combination with durvalumab, 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. IMJUDO with Durvalumab and Platinum-Based Chemotherapy Immune-mediated rash or dermatitis occurred in 7.2% (43/596) of patients receiving IMJUDO in combination with durvalumab and platinum-based chemotherapy, 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 IMJUDO in combination with durvalumab can cause immune-mediated pancreatitis. IMJUDO with Durvalumab Immune-mediated pancreatitis occurred in 2.3% (9/388) of patients receiving IMJUDO in combination with durvalumab, 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 IMJUDO in combination with durvalumab or were reported with the use of other immune-checkpoint inhibitors. 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: Gastritis, duodenitis. Musculoskeletal and connective tissue disorders: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica. Endocrine: Hypoparathyroidism. Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, and immune thrombocytopenia. 5.2 Infusion-Related Reactions IMJUDO in combination with durvalumab 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 IMJUDO and durvalumab based on the severity [see Dosage and Administration (2.2) ] . For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. IMJUDO with Durvalumab Infusion-related reactions occurred in 10 (2.6%) patients receiving IMJUDO in combination with durvalumab. IMJUDO with Durvalumab and Platinum-Based Chemotherapy Infusion-related reactions occurred in 2.9% (17/596) of patients receiving IMJUDO in combination with durvalumab and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions. 5.3 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, IMJUDO can cause fetal harm when administered to a pregnant woman. In animal studies, CTLA-4 blockade is associated with higher incidence of pregnancy loss. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMJUDO and for 3 months after the last dose of IMJUDO [see Use in Specific Populations (8.1 , 8.3 )]."],"clinical_studies_table":["<table width=\"100%\"><caption>Table 9. Efficacy Results for HIMALAYA Study</caption><col width=\"46%\"/><col width=\"26%\"/><col width=\"28%\"/><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\">IMJUDO and Durvalumab</content></paragraph><paragraph><content styleCode=\"bold\">(N=393)</content></paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Sorafenib</content></paragraph><paragraph><content styleCode=\"bold\">(N=389)</content></paragraph></td></tr><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 align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>262 (66.7)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>293 (75.3)</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 Lrule Toprule Botrule \" valign=\"top\"><paragraph>16.4</paragraph><paragraph>(14.2, 19.6)</paragraph></td><td align=\"center\" 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=\"_Ref117252005\">HR (IMJUDO and durvalumab vs. sorafenib) based on the stratified Cox proportional hazard model.</footnote></paragraph></td><td align=\"center\" 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\"><list listType=\"ordered\"><item><caption> </caption>p-value<footnote ID=\"_Ref117251886\">Based on a stratified log-rank test.</footnote><footnote ID=\"_Ref117251901\">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 IMJUDO and durvalumab vs. sorafenib was 0.0398 (Lan and DeMets 1983).</footnote></item></list></td><td align=\"center\" 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 align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>335 (85.2)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>327 (84.1)</paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph> Median PFS (months) </paragraph><paragraph> (95% CI)</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>3.8 </paragraph><paragraph>(3.7, 5.3)</paragraph></td><td align=\"center\" 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=\"_Ref117252005\"/></paragraph></td><td align=\"center\" 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\"><list listType=\"ordered\"><item><caption> </caption>ORR % (95% CI)<footnote ID=\"_Ref117252028\">Confirmed complete response or partial response.</footnote><footnote ID=\"_Ref117252045\">Based on Clopper-Pearson method.</footnote></item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>20.1 (16.3, 24.4)</paragraph></td><td align=\"center\" 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\"><list listType=\"ordered\"><item><caption> </caption>Complete Response n (%)</item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>12 (3.1)</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\"><list listType=\"ordered\"><item><caption> </caption>Partial Response n (%)</item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>67 (17.0)</paragraph></td><td align=\"center\" 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><content styleCode=\"bold\">DoR</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>Median DoR (months) </item><item><caption> </caption>(95% CI)</item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>22.3 (13.7, NR)</paragraph></td><td align=\"center\" 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\"><list listType=\"ordered\"><item><caption> </caption>% with duration &#x2265; 6 months</item></list></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>82.3</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>78.9</paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><list listType=\"ordered\"><item><caption> </caption>% with duration &#x2265; 12 months</item></list></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>65.8</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>63.2</paragraph></td></tr></tbody></table>","<table cellpadding=\"0pt\" width=\"100%\"><caption>Table 10. Efficacy Results for POSEIDON</caption><col width=\"41%\"/><col width=\"30%\"/><col width=\"30%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"/><td align=\"center\" styleCode=\"Rrule Botrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMJUDO with durvalumab 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=\"_Ref119394422\">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\"><paragraph> HR (95% CI) </paragraph></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=\"_Ref119394493\">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=\"_Ref119394422\"/></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 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\"><paragraph> HR (95% CI) </paragraph></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=\"_Ref119394493\"/> </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=\"_Ref119394529\">Confirmed responses with 95% Clopper-Pearson confidence intervals.</footnote></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 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 Botrule \" valign=\"top\"><paragraph>9.5</paragraph><paragraph>(7.2, NR)</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule \" valign=\"top\"><paragraph>5.1</paragraph><paragraph>(4.4, 6.0)</paragraph></td></tr><tr><td colspan=\"3\" styleCode=\"Toprule \" valign=\"top\"><paragraph>NR=Not Reached, CI=Confidence Interval</paragraph></td></tr></tbody></table>"],"nonclinical_toxicology":["13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenic and genotoxic potential of tremelimumab-actl have not been evaluated. Animal fertility studies have not been conducted with tremelimumab-actl."],"adverse_reactions_table":["<table styleCode=\"Noautorules\" width=\"100%\"><caption>Table 5. Adverse Reactions Occurring in &#x2265; 10% Patients in the HIMALAYA study</caption><col width=\"38%\"/><col width=\"15%\"/><col width=\"15%\"/><col width=\"15%\"/><col width=\"17%\"/><thead><tr><th align=\"left\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"/><th align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">IMJUDO and Durvalumab</content> <content styleCode=\"bold\">(N=388)</content></th><th align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><content styleCode=\"bold\">Sorafenib</content> <content styleCode=\"bold\">(N=374)</content></th></tr><tr><th align=\"left\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><content styleCode=\"bold\">Adverse Reaction</content></th><th align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">All Grades (%)</content></th><th align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">Grade 3-4 (%)</content></th><th align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">All Grades (%)</content></th><th align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">Grade 3-4 (%)</content></th></tr></thead><tbody><tr><td colspan=\"3\" styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Gastrointestinal disorders </content></paragraph></td><td colspan=\"2\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"/></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Diarrhea<footnote ID=\"_Ref117246862\">Represents a composite of multiple related terms.</footnote></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=\"_Ref117246862\"/></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\">Skin and subcutaneous tissue disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Rash<footnoteRef IDREF=\"_Ref117246862\"/></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=\"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=\"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=\"_Ref117246862\"/></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=\"_Ref117246862\"/></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=\"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 Lrule Botrule \" valign=\"top\"><paragraph>Insomnia</paragraph></td><td align=\"center\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"bottom\"><paragraph>10</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>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 Lrule Botrule \" valign=\"middle\"><paragraph>Hypothyroidism<footnoteRef IDREF=\"_Ref117246862\"/></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=\"5\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">Musculoskeletal and Connective Tissue Disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><paragraph>Musculoskeletal pain<footnoteRef IDREF=\"_Ref117246862\"/></paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"bottom\"><paragraph>22</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>2.6</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"bottom\"><paragraph>17</paragraph></td><td align=\"center\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>0.8</paragraph></td></tr></tbody></table>","<table width=\"100%\"><caption>Table 6. 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\">IMJUDO and Durvalumab</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></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\">Any grade</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=\"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=\"top\"><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 7. Adverse Reactions (&#x2265; 10%) in Patients with NSCLC Who Received IMJUDO 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\">IMJUDO with durvalumab 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=\"middle\"><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\">Respiratory, thoracic and mediastinal disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Cough/Productive Cough<footnote ID=\"_Ref119323944\">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\">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=\"_Ref119324151\">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\">Endocrine disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Hypothyroidism<footnote ID=\"_Ref119324169\">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\">Skin and subcutaneous tissue disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Rash<footnote ID=\"_Ref119324192\">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>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 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 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=\"_Ref119324216\">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=\"_Ref119324233\">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=\"_Ref119324254\">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=\"_Hlk118647807\">Includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, 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\">Infections and Infestations</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>Pneumonia<footnote ID=\"_Ref119324284\">Includes lower respiratory tract infection, pneumocystis jirovecii pneumonia, pneumonia, pneumonia aspiration, 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=\"_Ref119324405\">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\">Nervous system disorders</content></paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Headache<footnote ID=\"_Ref119324426\">Includes headache, 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=\"100%\"><caption>Table 8: Select Laboratory Abnormalities (&#x2265; 10%) That Worsened from Baseline in Patients with NSCLC Who Received IMJUDO in the POSEIDON Study</caption><col width=\"29%\"/><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></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMJUDO with Durvalumab and Platinum-based chemotherapy</content></paragraph></td><td align=\"center\" colspan=\"2\" styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Platinum-based chemotherapy</content></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 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>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>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>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>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>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>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>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>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>4.0</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 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>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>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>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>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>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>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><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>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>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>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>"],"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 IMJUDO in combination with durvalumab, including [see Warnings and Precautions (5.1) ] : • Pneumonitis: Advise patients to contact their healthcare provider immediately for any new or worsening cough, chest pain, or shortness of breath. • Colitis: Advise patients to contact their healthcare provider immediately for diarrhea, blood or mucus in stools, or severe abdominal pain. • 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. • 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 aseptic meningitis, 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) ] . Embryo-Fetal Toxicity: • Advise females of reproductive potential that IMJUDO can cause harm to a fetus and to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.3) 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 IMJUDO [see Use in Specific Populations (8.3) ]. Lactation: • Advise female patients not to breastfeed while taking IMJUDO and for 3 months after the last dose [see Warnings and Precautions (5.3 ) and Use in Specific Populations (8.2) ] . Manufactured for: AstraZeneca Pharmaceuticals LP Wilmington, DE 19850 Manufactured By: AstraZeneca AB Södertälje, Sweden SE-15185 US License No. 2059 IMJUDO ® is a registered trademark of AstraZeneca group of companies. © AstraZeneca 2022"],"dosage_and_administration":["2 DOSAGE AND ADMINISTRATION • Administer IMJUDO as an intravenous infusion over 60 minutes after dilution. ( 2.3 ) • uHCC: Weight 30 kg and more: IMJUDO 300 mg as a single dose in combination with durvalumab 1,500 mg at Cycle 1/Day 1, followed by durvalumab as a single agent every 4 weeks ( 2.1 ) Weight less than 30 kg: IMJUDO 4 mg/kg as a single dose in combination with durvalumab 20 mg/kg at Cycle 1/Day 1, followed by durvalumab as a single agent every 4 weeks ( 2.1 ) • Metastatic NSCLC: Weight 30 kg and more: 75 mg every 3 weeks in combination with durvalumab 1,500 mg and platinum-based chemotherapy for 4 cycles, and then administer durvalumab 1,500 mg every 4 weeks as a single agent with histology-based pemetrexed therapy every 4 weeks, and a fifth dose of IMJUDO 75 mg in combination with durvalumab dose 6 at week 16 ( 2.1 ) Weight less than 30 kg: 1 mg/kg every 3 weeks in combination with durvalumab 20 mg/kg and platinum-based chemotherapy for 4 cycles, and then administer durvalumab 20 mg/kg every 4 weeks as a single agent with histology-based pemetrexed therapy every 4 weeks, and a fifth dose of IMJUDO 1 mg/kg in combination with durvalumab dose 6 at week 16 ( 2.1 ) • See full Prescribing Information for preparation and administration instructions and dosage modifications for adverse reactions. 2.1 Recommended Dosage The recommended dosages of IMJUDO are presented in Tables 1, 2 and 3. Administer IMJUDO as an intravenous infusion after dilution as recommended [see Dosage and Administration (2.3) ]. IMJUDO in Combination with Durvalumab Table 1. Recommended dosage of IMJUDO Indication Recommended IMJUDO Dosage Duration of Therapy uHCC Patients with a body weight of 30 kg and more : • A single dose of IMJUDO Administer IMJUDO prior to durvalumab on the same day. 300 mg followed by durvalumab Refer to the Prescribing Information for durvalumab dosing information. 1,500 mg at Day 1 of Cycle 1; • Continue durvalumab 1,500 mg as a single agent every 4 weeks Patients with a body weight of less than 30 kg: • A single dose of IMJUDO 4 mg/kg followed by durvalumab 20 mg/kg at Day 1 of Cycle 1; • Continue durvalumab 20 mg/kg as a single agent every 4 weeks After Cycle 1 of combination therapy, administer durvalumab as a single agent every 4 weeks until disease progression or unacceptable toxicity IMJUDO in Combination with Durvalumab and Platinum-Based Chemotherapy The recommended dosage schedule and regimens for IMJUDO for the treatment of metastatic non-small cell lung cancer (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 Week continue durvalumab until disease progression or intolerable toxicity. , 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 IMJUDO intravenous infusion over 60 minutes [see Dosage and Administration (2.3) ]. , if patients receive fewer than 4 cycles of platinum-based chemotherapy, the remaining cycles of IMJUDO (up to a total of 5) should be given after the platinum-based chemotherapy phase, in combination with durvalumab, every 4 weeks. X X X X X Durvalumab , X X X 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 Tumor Histology Patient Weight IMJUDO Dosage Durvalumab Refer to the Prescribing Information for dosing information. Dosage Platinum-based Chemotherapy Regimen Non-Squamous ≥ 30 kg 75 mg 1,500 mg • carboplatin & nab-paclitaxel OR • carboplatin or cisplatin & pemetrexed < 30 kg 1 mg/kg 20 mg/kg Squamous ≥ 30 kg 75 mg 1,500 mg • carboplatin & nab-paclitaxel OR • carboplatin or cisplatin & gemcitabine < 30 kg 1 mg/kg 20 mg/kg 2.2 Dosage Modifications for Adverse Reactions No dose reduction for treatment is recommended. In general, withhold treatment regimen for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue treatment regimen 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. Recommended treatment modifications are presented 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 steroids 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 or 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 durvalumab 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 2.3 Preparation and Administration Preparation • Visually inspect drug product for particulate matter and discoloration. Discard 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 IMJUDO and discard the vial with any unused portion. • Transfer into an intravenous bag containing 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP and dilute to a concentration between 0.1 mg/mL and 10 mg/mL. Mix diluted solution by gentle inversion. Do not shake the solution. Storage of Diluted IMJUDO Infusion Solution • IMJUDO does not contain a preservative. Administer infusion solution immediately once prepared. If infusion solution is not administered immediately and needs to be stored, the total time from preparation to the start of administration should not exceed: 24 hours in a refrigerator at 2°C to 8°C (36°F to 46°F) 24 hours at room temperature up to 30°C (86°F) • Do not freeze. • Do not shake. Administration • Administer IMJUDO infusion solution intravenously over 60 minutes through an intravenous line containing a sterile, low-protein binding 0.2 or 0.22 micron filter. • Use separate infusion bags and filters for each drug product. IMJUDO In Combination with Other Products • Administer all drug products as separate intravenous infusions. • Do not co-administer other drugs through the same infusion line. • For platinum-based chemotherapy, refer to Prescribing Information for administration information. • For pemetrexed treatment, refer to Prescribing Information for administration information. Combination Regimens: Order of Infusions IMJUDO in Combination with Durvalumab • Infuse IMJUDO, followed by durvalumab on the same day of dosing. IMJUDO in Combination with Durvalumab and Platinum-based Chemotherapy • Infuse IMJUDO first, followed by durvalumab and then platinum-based chemotherapy on the day of dosing. IMJUDO in Combination with Durvalumab and Pemetrexed Therapy • Infuse IMJUDO first, followed by durvalumab and then pemetrexed treatment on the day of dosing. Combination Regimens: Infusion Instructions IMJUDO in Combination with Durvalumab • Observe patient for 60 minutes following completion of IMJUDO infusion [see Warnings and Precautions (5.2) ] . Then administer durvalumab as a separate intravenous infusion over 60 minutes IMJUDO in Combination with Durvalumab and Platinum-based Chemotherapy/ Pemetrexed Therapy Cycle 1: Infuse IMJUDO over one hour. One to two hours after completion of IMJUDO infusion, infuse durvalumab over one hour. One to two hours after completion of durvalumab infusion, administer platinum-based chemotherapy. Subsequent Cycles: If there are no infusion reactions during cycle 1, subsequent cycles of durvalumab can be given immediately after IMJUDO. The time between the end of the durvalumab infusion and the start of chemotherapy can be reduced to 30 minutes."],"spl_product_data_elements":["IMJUDO tremelimumab TREMELIMUMAB TREMELIMUMAB EDETATE DISODIUM HISTIDINE HISTIDINE MONOHYDROCHLORIDE MONOHYDRATE POLYSORBATE 80 TREHALOSE WATER IMJUDO tremelimumab TREMELIMUMAB TREMELIMUMAB EDETATE DISODIUM HISTIDINE HISTIDINE MONOHYDROCHLORIDE MONOHYDRATE POLYSORBATE 80 TREHALOSE WATER"],"dosage_forms_and_strengths":["3 DOSAGE FORMS AND STRENGTHS Injection: 25 mg/1.25 mL (20 mg/mL) or 300 mg/15 mL (20 mg/mL) clear to slightly opalescent, colorless to slightly yellow solution in a single-dose vial. • Injection: 25 mg/1.25 mL (20 mg/mL) solution in a single-dose vial. ( 3 ) • Injection: 300 mg/15 mL (20 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, IMJUDO can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of IMJUDO in pregnant women. In animal studies, CTLA-4 blockade is associated with increased risk of immune-mediated rejection of the developing fetus and fetal death ( see Data ). Human immunoglobulin G2 (IgG2) is known to cross the placental barrier; therefore, IMJUDO has the potential to be transmitted from the mother to the developing fetus. Advise pregnant women and females of reproductive potential 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 In a reproduction study, administration of tremelimumab-actl to pregnant cynomolgus monkeys during the period of organogenesis was not associated with maternal toxicity or effects on embryo-fetal development at exposure levels approximately 4 to 31-times higher than those observed at a recommended dose range of 75 mg to 300 mg based on area under the curve (AUC). CTLA-4 plays a role in maintaining maternal immune tolerance to the fetus to preserve pregnancy and in immune regulation of the newborn. In a murine model of pregnancy, CTLA-4 blockade resulted in increased resorptions and reduced live fetuses. Mated genetically engineered mice heterozygous for CTLA-4 (CTLA-4+/-) gave birth to CTLA-4+/- offspring and offspring deficient in CTLA-4 (homozygous negative, CTLA-4-/-) that appeared healthy at birth. The CTLA-4-/- homozygous negative offspring developed signs of a lymphoproliferative disorder and died by 3 to 4 weeks of age with multiorgan tissue destruction. Based on its mechanism of action, fetal exposure to tremelimumab-actl may increase the risk of developing immune-mediated disorders or altering the normal immune response. 8.2 Lactation Risk Summary There are no data on the presence of tremelimumab-actl in human milk, its effects on a breastfed child, or 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 IMJUDO are unknown. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with IMJUDO and for 3 months after the last dose. Refer to the Prescribing Information for agents administered in combination with IMJUDO for breastfeeding recommendations, as appropriate. 8.3 Females and Males of Reproductive Potential IMJUDO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify pregnancy status of females of reproductive potential prior to initiating treatment with IMJUDO. Contraception Advise females of reproductive potential to use effective contraception during treatment with IMJUDO and for 3 months after the last dose. Refer to the Prescribing Information for the agents administered in combination with IMJUDO for recommended contraception duration, as appropriate. 8.4 Pediatric Use The safety and effectiveness of IMJUDO have not been established in pediatric patients. Safety and efficacy were assessed but not established in a multi-center, open-label study (NCT03837899) in which 41 pediatric patients aged 1 to < 17 years with advanced solid tumors received IMJUDO in combination with durvalumab. No new safety signals were observed in pediatric patients in this study. Tremelimumab-actl systemic exposure in pediatric patients ≥ 35 kg was within the range of the values previously observed in adults given the same weight-based dose, whereas the systemic exposure in pediatric patients < 35 kg was lower than that of adults. 8.5 Geriatric Use Of the 393 patients with uHCC treated with IMJUDO in combination with durvalumab, 50% of patients were 65 years or older and 13% of patients were 75 years or older. No overall differences in safety or efficacy of IMJUDO have been observed between patients 65 years or older and younger adult patients. Of the 330 patients with metastatic NSCLC treated with IMJUDO in combination with durvalumab and platinum-based chemotherapy, 143 (43%) patients were 65 years or older and 35 (11%) patients were 75 years or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects."],"dosage_and_administration_table":["<table styleCode=\"Noautorules\" width=\"100%\"><caption>Table 1. Recommended dosage of IMJUDO</caption><col width=\"33%\"/><col width=\"33%\"/><col width=\"33%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Indication</content></paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Recommended IMJUDO Dosage</content></paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Duration of Therapy</content></paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>uHCC</paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"underline\">Patients with a body weight of 30 kg and more</content>:</paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption>A single dose of IMJUDO<footnote ID=\"_Ref216257787\">Administer IMJUDO prior to durvalumab on the same day.</footnote> 300 mg followed by durvalumab<footnote ID=\"_Ref216257942\">Refer to the Prescribing Information for durvalumab dosing information.</footnote> 1,500 mg at Day 1 of Cycle 1;</item><item><caption>&#x2022;</caption>Continue durvalumab 1,500 mg as a single agent every 4 weeks</item></list><paragraph><content styleCode=\"underline\">Patients with a body weight of less than 30 kg:</content></paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption>A single dose of IMJUDO<footnoteRef IDREF=\"_Ref216257787\"/> 4 mg/kg followed by durvalumab 20 mg/kg at Day 1 of Cycle 1;</item><item><caption>&#x2022;</caption>Continue durvalumab 20 mg/kg as a single agent every 4 weeks</item></list></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>After Cycle 1 of combination therapy, administer durvalumab as a single agent every 4 weeks until disease progression or unacceptable toxicity</paragraph></td></tr></tbody></table>","<table styleCode=\"Noautorules\" width=\"100%\"><caption>Table 2: Recommended Dosage Schedule</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<footnote ID=\"_Ref119310912\">continue durvalumab until disease progression or intolerable toxicity.</footnote>,<footnote ID=\"_Ref119311125\">dosing interval change from every 3 weeks to every 4 weeks starting at cycle 5.</footnote></content></th></tr><tr><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">0</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">1</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">2</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">3</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">4</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">5</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">6</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">7</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">8</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">9</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">10</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">11</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">12</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">13</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">14</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">15</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">16</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">17</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">18</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">19</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">20</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">21</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">22</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">23</content></th><th align=\"left\" styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><content styleCode=\"bold\">24</content></th></tr></thead><tbody><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Cycle:</content></paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">1</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\"><paragraph><content styleCode=\"bold\">2</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\"><paragraph><content styleCode=\"bold\">3</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\"><paragraph><content styleCode=\"bold\">4</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\"><paragraph><content styleCode=\"bold\">5</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\"><paragraph><content styleCode=\"bold\">6</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\"><paragraph><content styleCode=\"bold\">7</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\"><paragraph><content styleCode=\"bold\">8</content></paragraph></td></tr><tr><td styleCode=\"Rrule Lrule Botrule \" valign=\"top\"><paragraph>IMJUDO<footnote ID=\"_Ref119311150\">intravenous infusion over 60 minutes <content styleCode=\"italics\">[see <linkHtml href=\"#ID_aa1efdae-e7a9-452f-ad05-c22daabf50b0\">Dosage and Administration (2.3)</linkHtml>].</content></footnote>,<footnote ID=\"_Ref119311162\">if patients receive fewer than 4 cycles of platinum-based chemotherapy, the remaining cycles of IMJUDO (up to a total of 5) should be given after the platinum-based chemotherapy phase, in combination with durvalumab, every 4 weeks.</footnote></paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">X</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\"><paragraph><content styleCode=\"bold\">X</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\"><paragraph><content styleCode=\"bold\">X</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\"><paragraph><content styleCode=\"bold\">X</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\"/><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><content styleCode=\"bold\">X</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\"/><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>Durvalumab<footnoteRef IDREF=\"_Ref119310912\"/>,<footnoteRef IDREF=\"_Ref119311150\"/></paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph><content styleCode=\"bold\">X</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\"><paragraph><content styleCode=\"bold\">X</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\"><paragraph><content styleCode=\"bold\">X</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\"><paragraph><content styleCode=\"bold\">X</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\"><paragraph><content styleCode=\"bold\">X</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\"><paragraph><content styleCode=\"bold\">X</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\"><paragraph><content styleCode=\"bold\">X</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\"><paragraph><content styleCode=\"bold\">X</content></paragraph></td></tr><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>Chemotherapy</paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">X</content></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><content styleCode=\"bold\">X</content></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><content styleCode=\"bold\">X</content></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><content styleCode=\"bold\">X</content></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><content styleCode=\"bold\">X<footnote ID=\"_Ref119311209\">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></content></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><content styleCode=\"bold\">X<footnoteRef IDREF=\"_Ref119311209\"/></content></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><content styleCode=\"bold\">X<footnoteRef IDREF=\"_Ref119311209\"/></content></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><content styleCode=\"bold\">X<footnoteRef IDREF=\"_Ref119311209\"/></content></paragraph></td></tr></tbody></table>","<table styleCode=\"Noautorules\" width=\"100%\"><caption>Table 3: Recommended Regimen and Dosage</caption><col width=\"20%\"/><col width=\"17%\"/><col width=\"14%\"/><col width=\"16%\"/><col width=\"33%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Tumor Histology</content></paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Patient Weight</content></paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">IMJUDO</content></paragraph><paragraph><content styleCode=\"bold\">Dosage</content></paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Durvalumab</content><footnote ID=\"_Ref216267430\">Refer to the Prescribing Information for dosing information.</footnote></paragraph><paragraph><content styleCode=\"bold\">Dosage</content></paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph><content styleCode=\"bold\">Platinum-based</content></paragraph><paragraph><content styleCode=\"bold\">Chemotherapy Regimen</content><footnoteRef IDREF=\"_Ref216267430\"/></paragraph></td></tr><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>75 mg</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1,500 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>1 mg/kg</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>20 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>75 mg</paragraph></td><td styleCode=\"Rrule Lrule Toprule Botrule \" valign=\"top\"><paragraph>1,500 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>1 mg/kg</paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"top\"><paragraph>20 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=\"21%\"/><col width=\"46%\"/><tbody><tr><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">Adverse Reaction</content></paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">Severity</content><footnote ID=\"_Ref83981218\">Based on National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03.</footnote></paragraph></td><td styleCode=\"Rrule Botrule Lrule Toprule \" valign=\"middle\"><paragraph><content styleCode=\"bold\">Dosage Modification</content></paragraph></td></tr><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_699d0321-40fd-4962-9807-abb816567b14\">Warnings and Precautions (5.1)</linkHtml>]</content></content></paragraph></td></tr><tr><td rowspan=\"2\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph>Pneumonitis </paragraph></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=\"_Ref119312382\">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 steroids 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=\"2\" styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph>Colitis </paragraph></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=\"_Ref119312382\"/></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 styleCode=\"Rrule Lrule Botrule \" valign=\"middle\"><paragraph>Intestinal perforation</paragraph></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\"><paragraph>Hepatitis with no tumor involvement of the liver</paragraph></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=\"_Ref119312382\"/></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\"><paragraph>Hepatitis with tumor involvement of the liver<footnote ID=\"_Ref119312455\">If AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue durvalumab based on recommendations for hepatitis with no liver involvement.</footnote></paragraph></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=\"_Ref119312382\"/></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\"><paragraph>Endocrinopathies </paragraph></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\"><paragraph>Nephritis with Renal Dysfunction </paragraph></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=\"_Ref119312382\"/></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\"><paragraph>Exfoliative Dermatologic Conditions</paragraph></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=\"_Ref119312382\"/></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\"><paragraph>Myocarditis</paragraph></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\"><paragraph>Neurological Toxicities</paragraph></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=\"_Ref119312382\"/></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\"><paragraph>Infusion-related reactions <content styleCode=\"italics\">[see <linkHtml href=\"#ID_e8b27574-33f7-46ed-8eeb-fa003e0b6f7a\">Warnings and Precautions (5.2)</linkHtml>]</content></paragraph></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>"],"package_label_principal_display_panel":["PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 0310-4535-30 Rx only IMJUDO® 300 mg/15 mL (tremelimumab-actl) (20 mg/mL) Injection For Intravenous Infusion After Dilution Single-dose vial. Discard unused portion. Attention Pharmacist: Dispense the accompanying Medication Guide to each patient. AstraZeneca 300_mg","PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 0310-4505-25 Rx only IMJUDO® 25 mg/1.25 mL (tremelimumab-actl) (20 mg/mL) Injection For Intravenous Infusion After Dilution Single-dose vial. Discard unused portion. Attention Pharmacist: Dispense the accompanying Medication Guide to each patient. AstraZeneca 25_mg"],"carcinogenesis_and_mutagenesis_and_impairment_of_fertility":["13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenic and genotoxic potential of tremelimumab-actl have not been evaluated. Animal fertility studies have not been conducted with tremelimumab-actl."]},"tags":[{"label":"Monoclonal Antibody","category":"modality"},{"label":"Cytotoxic T-lymphocyte protein 4","category":"target"},{"label":"CTLA4","category":"gene"},{"label":"L01FX20","category":"atc"},{"label":"Intravenous","category":"route"},{"label":"Injection","category":"form"},{"label":"Active","category":"status"},{"label":"Liver cell carcinoma","category":"indication"},{"label":"Metastatic non-small cell lung cancer with no anaplastic lymphoma kinase genomic tumor aberrations","category":"indication"},{"label":"Non-small cell lung cancer, negative for epidermal growth factor receptor expression","category":"indication"},{"label":"Astrazeneca Ab","category":"company"},{"label":"Approved 2020s","category":"decade"},{"label":"Antineoplastic Agents","category":"pharmacology"}],"phase":"marketed","safety":{"boxedWarnings":[],"safetySignals":[{"date":"","signal":"DEATH","source":"FDA FAERS","actionTaken":"279 reports"},{"date":"","signal":"DIARRHOEA","source":"FDA FAERS","actionTaken":"255 reports"},{"date":"","signal":"PYREXIA","source":"FDA FAERS","actionTaken":"206 reports"},{"date":"","signal":"MALIGNANT NEOPLASM PROGRESSION","source":"FDA FAERS","actionTaken":"193 reports"},{"date":"","signal":"COLITIS","source":"FDA FAERS","actionTaken":"164 reports"},{"date":"","signal":"CYTOKINE RELEASE SYNDROME","source":"FDA FAERS","actionTaken":"152 reports"},{"date":"","signal":"IMMUNE-MEDIATED ENTEROCOLITIS","source":"FDA FAERS","actionTaken":"126 reports"},{"date":"","signal":"RASH","source":"FDA FAERS","actionTaken":"123 reports"},{"date":"","signal":"LIVER DISORDER","source":"FDA FAERS","actionTaken":"112 reports"},{"date":"","signal":"PNEUMONIA","source":"FDA FAERS","actionTaken":"106 reports"}],"commonSideEffects":[{"effect":"Nausea","drugRate":"37%","severity":"common","_validated":true},{"effect":"Diarrhea","drugRate":"","severity":"common","_validated":false,"_confidence":0.3},{"effect":"Fatigue","drugRate":"22%","severity":"common","_validated":true},{"effect":"Decreased appetite","drugRate":"25%","severity":"common","_validated":true},{"effect":"Rash","drugRate":"","severity":"common","_validated":false,"_confidence":0.3},{"effect":"Abdominal pain","drugRate":"","severity":"serious","_validated":false,"_confidence":0.3},{"effect":"Musculoskeletal pain","drugRate":"","severity":"common","_validated":false,"_confidence":0.3},{"effect":"Pruritus","drugRate":"23%","severity":"common","_validated":true},{"effect":"Hemorrhage","drugRate":"6%","severity":"serious","_validated":true},{"effect":"Neutropenia","drugRate":"39%","severity":"serious","_validated":true},{"effect":"Leukopenia","drugRate":"21%","severity":"serious","_validated":true},{"effect":"Lymphocytopenia","drugRate":"20%","severity":"serious","_validated":true},{"effect":"Anemia","drugRate":"20%","severity":"serious","_validated":true},{"effect":"Hyponatremia","drugRate":"14%","severity":"mild","_validated":true},{"effect":"Lipase increased","drugRate":"12%","severity":"mild","_validated":true},{"effect":"Thrombocytopenia","drugRate":"11%","severity":"mild","_validated":true},{"effect":"ALT increased","drugRate":"","severity":"mild","_validated":false,"_confidence":0.3},{"effect":"AST increased","drugRate":"","severity":"mild","_validated":false,"_confidence":0.3},{"effect":"Pneumonia","drugRate":"2.1%","severity":"serious","_validated":true},{"effect":"Sepsis","drugRate":"2.1%","severity":"serious","_validated":true},{"effect":"Pyrexia","drugRate":"1.3%","severity":"mild","_validated":true},{"effect":"Vomiting","drugRate":"1.3%","severity":"mild","_validated":true},{"effect":"Acute kidney injury","drugRate":"1.3%","severity":"serious","_validated":true},{"effect":"Hepatitis","drugRate":"1%","severity":"serious","_validated":true},{"effect":"Insomnia","drugRate":"1%","severity":"unknown","_validated":true},{"effect":"Hypothyroidism","drugRate":"1%","severity":"unknown","_validated":true},{"effect":"Pneumonitis","drugRate":"0.5%","severity":"serious","_validated":true},{"effect":"Cardiac arrest","drugRate":"0.5%","severity":"serious","_validated":true},{"effect":"Hepatic failure","drugRate":"0.5%","severity":"serious","_validated":true}],"specialPopulations":{"Lactation":"There are no data on the presence of tremelimumab-actl in human milk, its effects on breastfed child, or 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 IMJUDO are unknown. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with IMJUDO and for months after the last dose.","Pregnancy":"IMJUDO can cause fetal harm when administered to pregnant woman. There are no available data on the use of IMJUDO in pregnant women. In animal studies, CTLA-4 blockade is associated with increased risk of immune-mediated rejection of the developing fetus and fetal death. Human immunoglobulin G2 (IgG2) is known to cross the placental barrier; therefore, IMJUDO has the potential to be transmitted from the mother to the developing fetus. Advise pregnant women and females of reproductive potential of the potential risk to fetus.","Geriatric use":"No overall differences in safety or efficacy of IMJUDO have been observed between patients 65 years or older and younger adult patients.","Paediatric use":"The safety and effectiveness of tremelimumab-actl have not been established in pediatric patients."}},"trials":[],"aliases":[],"company":"AstraZeneca","patents":[{"type":"Biologic Exclusivity","filed":"October 21, 2022","source":"FDA Purple Book","status":"Active","expires":"October 21, 2029","territory":"US","patentNumber":"BLA 761289"}],"pricing":[],"_sources":{"trials":{"url":"https://clinicaltrials.gov/search?intr=TREMELIMUMAB","method":"api_direct","source":"ClinicalTrials.gov","rawText":"","confidence":1,"sourceType":"ctgov","retrievedAt":"2026-04-20T02:04:25.185907+00:00"},"patents":{"url":"","method":"deterministic","source":"FDA Orange Book","rawText":"","confidence":1,"sourceType":"fda_orange_book","retrievedAt":"2026-04-20T02:04:21.833743+00:00"},"timeline":{"url":"https://en.wikipedia.org/wiki/Tremelimumab","method":"deterministic","source":"Wikipedia","rawText":"","confidence":0.8,"sourceType":"wikipedia","retrievedAt":"2026-04-20T02:04:28.209293+00:00"},"regulatory.ca":{"url":"","method":"api_direct","source":"Health Canada DPD","rawText":"","confidence":1,"sourceType":"health_canada_dpd","retrievedAt":"2026-04-20T02:04:26.993187+00:00"},"regulatory.eu":{"url":"","method":"api_direct","source":"European Medicines Agency","rawText":"","confidence":1,"sourceType":"ema_api","retrievedAt":"2026-04-20T02:04:25.208815+00:00"},"regulatory.us":{"url":"","method":"api_direct","source":"FDA Drugs@FDA","rawText":"","confidence":1,"sourceType":"fda_drugsfda","retrievedAt":"2026-04-20T02:04:20.437209+00:00"},"publicationCount":{"url":"https://pubmed.ncbi.nlm.nih.gov/?term=TREMELIMUMAB","method":"api_direct","source":"PubMed/NCBI","rawText":"","confidence":1,"sourceType":"pubmed","retrievedAt":"2026-04-20T02:04:27.659999+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":"2026-04-20T02:04:19.286828+00:00"},"administration.route":{"url":"","method":"deterministic","source":"FDA Label","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T02:04:19.286890+00:00"},"safety.boxedWarnings":{"url":"","method":"deterministic","source":"FDA Label (no boxed warning)","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T02:04:19.286904+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":"2026-04-20T02:04:29.113435+00:00"},"mechanism.oneSentence":{"url":"","method":"ai_extraction","source":"FDA Label + AI","aiModel":"featherless","rawText":"12.1 Mechanism of Action CTLA-4 is a negative regulator of T-cell activity. Tremelimumab-actl is a monoclonal antibody that binds to CTLA-4 and blocks the interaction with its ligands CD80 and CD86, releasing CTLA-4-mediated inhibition of T-cell activation. In synergistic mouse tumor models, blocking CTLA-4 activity resulted in decreased tumor growth and increased proliferation of T cells in tumors.","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T02:04:41.759610+00:00"},"mechanism.target_chembl":{"url":"","method":"api_direct","source":"ChEMBL mechanism: Cytotoxic T-lymphocyte protein 4 inhibitor","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-20T02:04:28.208936+00:00"},"crossReferences.chemblId":{"url":"https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL2108658/","method":"api_direct","source":"ChEMBL (EMBL-EBI)","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-20T02:04:28.112961+00:00"},"regulatory.fda_application":{"url":"","method":"deterministic","source":"FDA Label","rawText":"BLA761289","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T02:04:19.286913+00:00"}},"allNames":"imjudo","offLabel":[],"synonyms":["tremelimumab","tremelimumab-actl","CP-675206","imjudo","tremelimumab (genetical recombination)"],"timeline":[{"date":"2022-10-21","type":"positive","source":"DrugCentral","milestone":"FDA approval (Astrazeneca Ab)"},{"date":"2023-02-20","type":"positive","source":"DrugCentral","milestone":"EMA approval (Astrazeneca Ab)"},{"date":"2023-12-23","type":"positive","source":"DrugCentral","milestone":"PMDA approval (AstraZeneca K.K.)"}],"approvals":[{"date":"2022-10-21","orphan":true,"company":"ASTRAZENECA AB","regulator":"FDA"},{"date":"2023-02-20","orphan":false,"company":"ASTRAZENECA AB","regulator":"EMA"},{"date":"2023-12-23","orphan":false,"company":"AstraZeneca K.K.","regulator":"PMDA"}],"brandName":"Imjudo","ecosystem":[{"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":"durvalumab","slug":"durvalumab","company":"Astrazeneca Uk Ltd"}],"globalPrevalence":null},{"indication":"Metastatic non-small cell lung cancer with no anaplastic lymphoma kinase genomic tumor aberrations","otherDrugs":[],"globalPrevalence":2200000},{"indication":"Non-small cell lung cancer, negative for epidermal growth factor receptor expression","otherDrugs":[],"globalPrevalence":2200000}],"mechanism":{"target":"CTLA-4","novelty":"Follow-on","targets":[{"gene":"CTLA4","source":"DrugCentral","target":"Cytotoxic T-lymphocyte protein 4","protein":"Cytotoxic T-lymphocyte protein 4"}],"modality":"Monoclonal antibody","drugClass":"CTLA-4-directed Blocking Antibody [EPC]","explanation":"Tremelimumab-actl is designed to bind to CTLA-4, a protein that normally inhibits T-cell activity. By blocking CTLA-4, the drug removes this inhibition, leading to increased T-cell activation and proliferation, which can help combat tumors.","oneSentence":"Tremelimumab-actl binds to CTLA-4, blocking its interaction with CD80 and CD86, thereby enhancing T-cell activation and reducing tumor growth.","technicalDetail":"CTLA-4 is a negative regulator of T-cell activity. Tremelimumab-actl is a monoclonal antibody that binds to CTLA-4 and blocks the interaction with its ligands CD80 and CD86, releasing CTLA-4-mediated inhibition of T-cell activation."},"_wikipedia":{"url":"https://en.wikipedia.org/wiki/Tremelimumab","title":"Tremelimumab","extract":"Tremelimumab, sold under the brand name Imjudo, is a fully human monoclonal antibody used for the treatment of hepatocellular carcinoma. Tremelimumab is designed to attach to and block CTLA-4, a protein that controls the activity of T cells, which are part of the immune system.","wiki_history":"== History ==\nPreviously in development by Pfizer, it is in investigation by MedImmune, a wholly owned subsidiary of AstraZeneca.\n\n=== Clinical trials ===\n\n=== Melanoma ===\nPhase I and II clinical studies in metastatic melanoma showed some responses. However, based on early interim analysis of phase III data, Pfizer designated tremelimumab as a failure and terminated the trial in April 2008.\n\nHowever, within a year, the survival curves showed separation of the treatment and control groups.\n\n=== Mesothelioma ===\nAlthough it was designated in April 2015 as orphan drug status in mesothelioma, tremelimumab failed to improve lifespan in the phase IIb DETERMINE trial, which assessed the drug as a second or third-line treatment for unresectable malignant mesothelioma.\n\n=== Non-small cell lung cancer ===\nIn a phase III trial, AstraZeneca paired tremelimumab with a PD-L1 inhibitor, durvalumab, for the first-line treatment of non-small cell lung cancer. The trial was conducted across 17 countries, and in July 2017, AstraZeneca announced that it had failed to meet its primary endpoint of progression-free survival.","wiki_society_and_culture":"== Society and culture ==\n=== Legal status ===\nOn 15 December 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Imjudo, intended for the treatment of hepatocellular carcinoma. Tremelimumab was approved for medical use in the European Union in February 2023.\n\n=== Names ===\nTremelimumab is the international nonproprietary name (INN)."},"commercial":{"launchDate":"2022","revenueYear":2024,"_launchSource":"DrugCentral (FDA 2022-10-21, ASTRAZENECA AB)","annualRevenue":400,"revenueSource":"Verified: AstraZeneca AR","revenueCurrency":"USD","revenueConfidence":"verified"},"purpleBook":{"bla":"761289","source":"FDA Purple Book","approvalDate":"October 21, 2022","licenseStatus":"Licensed","exclusivityExpiry":"October 21, 2029"},"references":[{"id":1,"url":"https://drugcentral.org/drugcard/5690","fields":["approvals","synonyms","ATC","PK","indications","contraindications","DDIs","targets","patents","FAERS"],"source":"DrugCentral"},{"id":2,"url":"https://clinicaltrials.gov/search?intr=TREMELIMUMAB","fields":["trials"],"source":"ClinicalTrials.gov"},{"id":3,"url":"https://pubmed.ncbi.nlm.nih.gov/?term=TREMELIMUMAB","fields":["publications"],"source":"PubMed/NCBI"},{"id":4,"url":"https://en.wikipedia.org/wiki/Tremelimumab","fields":["history","overview"],"source":"Wikipedia"},{"id":5,"url":"https://purplebooksearch.fda.gov/","fields":["biologicExclusivity"],"source":"FDA Purple Book"}],"_emaChecked":true,"_enrichedAt":"2026-03-30T16:04:08.485888","_validation":{"fieldsValidated":1,"lastValidatedAt":"2026-04-20T02:04:45.647691+00:00","fieldsConflicting":6,"overallConfidence":0.8},"biosimilars":[],"competitors":[{"drugName":"gemtuzumab ozogamicin","drugSlug":"gemtuzumab-ozogamicin","fdaApproval":"2000-05-17","relationship":"same-class"},{"drugName":"ipilimumab","drugSlug":"ipilimumab","fdaApproval":"2011-03-25","relationship":"same-class"},{"drugName":"brentuximab vedotin","drugSlug":"brentuximab-vedotin","fdaApproval":"2011-08-19","relationship":"same-class"},{"drugName":"blinatumomab","drugSlug":"blinatumomab","fdaApproval":"2014-12-03","relationship":"same-class"},{"drugName":"elotuzumab","drugSlug":"elotuzumab","fdaApproval":"2015-11-30","relationship":"same-class"},{"drugName":"mogamulizumab","drugSlug":"mogamulizumab","fdaApproval":"2018-08-08","relationship":"same-class"},{"drugName":"olaratumab","drugSlug":"olaratumab","fdaApproval":"2016-10-19","relationship":"same-class"},{"drugName":"tafasitamab","drugSlug":"tafasitamab","fdaApproval":"2020-07-31","relationship":"same-class"},{"drugName":"enfortumab vedotin","drugSlug":"enfortumab-vedotin","fdaApproval":"2019-12-18","relationship":"same-class"},{"drugName":"polatuzumab vedotin","drugSlug":"polatuzumab-vedotin","fdaApproval":"2019-06-10","relationship":"same-class"},{"drugName":"belantamab mafodotin","drugSlug":"belantamab-mafodotin","fdaApproval":"2020-05-08","relationship":"same-class"},{"drugName":"sacituzumab govitecan","drugSlug":"sacituzumab-govitecan","fdaApproval":"2020-04-04","relationship":"same-class"},{"drugName":"amivantamab","drugSlug":"amivantamab","fdaApproval":"2021-05-21","relationship":"same-class"},{"drugName":"naxitamab","drugSlug":"naxitamab","fdaApproval":"2020-11-25","relationship":"same-class"},{"drugName":"loncastuximab tesirine","drugSlug":"loncastuximab-tesirine","fdaApproval":"2021-04-23","relationship":"same-class"},{"drugName":"tisotumab vedotin","drugSlug":"tisotumab-vedotin","fdaApproval":"2021-09-20","relationship":"same-class"}],"genericName":"tremelimumab","indications":{"approved":[{"name":"Liver cell carcinoma","source":"DrugCentral","snomedId":109841003,"regulator":"FDA","eligibility":"unresectable hepatocellular carcinoma (uHCC)"},{"name":"Metastatic non-small cell lung cancer with no anaplastic lymphoma kinase genomic tumor aberrations","source":"DrugCentral","snomedId":830055006,"regulator":"FDA","eligibility":"adult patients with metastatic NSCLC with no sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) genomic tumor aberrations","usPrevalence":236000,"globalPrevalence":2200000,"prevalenceMethod":"curated","prevalenceSource":"IARC GLOBOCAN, 2022"},{"name":"Non-small cell lung cancer, negative for epidermal growth factor receptor expression","source":"DrugCentral","snomedId":427038005,"regulator":"FDA","eligibility":"adult patients with metastatic NSCLC with no sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) genomic tumor aberrations","usPrevalence":236000,"globalPrevalence":2200000,"prevalenceMethod":"curated","prevalenceSource":"IARC GLOBOCAN, 2022"}],"offLabel":[],"pipeline":[]},"drugCategory":"active","labelChanges":[],"relatedDrugs":[{"drugId":"gemtuzumab-ozogamicin","brandName":"gemtuzumab ozogamicin","genericName":"gemtuzumab ozogamicin","approvalYear":"2000","relationship":"same-class"},{"drugId":"ipilimumab","brandName":"ipilimumab","genericName":"ipilimumab","approvalYear":"2011","relationship":"same-class"},{"drugId":"brentuximab-vedotin","brandName":"brentuximab vedotin","genericName":"brentuximab vedotin","approvalYear":"2011","relationship":"same-class"},{"drugId":"blinatumomab","brandName":"blinatumomab","genericName":"blinatumomab","approvalYear":"2014","relationship":"same-class"},{"drugId":"elotuzumab","brandName":"elotuzumab","genericName":"elotuzumab","approvalYear":"2015","relationship":"same-class"},{"drugId":"mogamulizumab","brandName":"mogamulizumab","genericName":"mogamulizumab","approvalYear":"2018","relationship":"same-class"},{"drugId":"olaratumab","brandName":"olaratumab","genericName":"olaratumab","approvalYear":"2016","relationship":"same-class"},{"drugId":"tafasitamab","brandName":"tafasitamab","genericName":"tafasitamab","approvalYear":"2020","relationship":"same-class"},{"drugId":"enfortumab-vedotin","brandName":"enfortumab vedotin","genericName":"enfortumab vedotin","approvalYear":"2019","relationship":"same-class"},{"drugId":"polatuzumab-vedotin","brandName":"polatuzumab vedotin","genericName":"polatuzumab vedotin","approvalYear":"2019","relationship":"same-class"}],"trialDetails":[{"nctId":"NCT04034927","phase":"PHASE2","title":"Testing the Addition of an Immunotherapy Drug, Tremelimumab, to the PARP Inhibition Drug, Olaparib, for Recurrent Ovarian, Fallopian Tube or Peritoneal Cancer","status":"ACTIVE_NOT_RECRUITING","sponsor":"National Cancer Institute (NCI)","startDate":"2019-12-04","conditions":["Fallopian Tube Endometrioid Tumor","Fallopian Tube High Grade Serous Adenocarcinoma","Malignant Ovarian Endometrioid Tumor","Ovarian High Grade Serous Adenocarcinoma","Platinum-Sensitive Fallopian Tube Carcinoma","Platinum-Sensitive Ovarian Carcinoma","Platinum-Sensitive Primary Peritoneal Carcinoma","Primary Peritoneal High Grade Serous Adenocarcinoma","Recurrent Fallopian Tube Carcinoma","Recurrent Fallopian Tube Endometrioid Adenocarcinoma","Recurrent Ovarian Endometrioid Adenocarcinoma","Recurrent Ovarian Serous Adenocarcinoma","Recurrent Primary Peritoneal Carcinoma","Recurrent Primary Peritoneal Endometrioid Adenocarcinoma"],"enrollment":61,"completionDate":"2027-02-21"},{"nctId":"NCT03606967","phase":"PHASE2","title":"Testing the Addition of an Individualized Vaccine to Durvalumab and Tremelimumab and Chemotherapy in Patients With Metastatic Triple Negative Breast Cancer","status":"RECRUITING","sponsor":"National Cancer Institute (NCI)","startDate":"2021-04-13","conditions":["Anatomic Stage IV Breast Cancer AJCC v8","Invasive Breast Carcinoma","Metastatic Triple-Negative Breast Carcinoma"],"enrollment":70,"completionDate":"2026-12-30"},{"nctId":"NCT06494540","phase":"","title":"NIS to Examine the Effectiveness of TDC in Patients With Metastatic Non-squamous NSCLC and High-risk Genetic Alterations","status":"RECRUITING","sponsor":"AstraZeneca","startDate":"2024-06-28","conditions":["Non-squamous Metastatic Non-Small-Cell Lung Carcinoma"],"enrollment":600,"completionDate":"2028-06-30"},{"nctId":"NCT06008093","phase":"PHASE2","title":"A Study to Investigate the Efficacy of Durvalumab Plus Tremelimumab in Combination With Chemotherapy Compared With Pembrolizumab in Combination With Chemotherapy in Metastatic NSCLC Patients With Non-squamous Histology Who Have Mutations and/or Co-mutations in STK11, KEAP1, or KRAS","status":"ACTIVE_NOT_RECRUITING","sponsor":"AstraZeneca","startDate":"2024-04-04","conditions":["Carcinoma, Non-Small-Cell Lung"],"enrollment":100,"completionDate":"2027-12-23"},{"nctId":"NCT02888743","phase":"PHASE2","title":"Durvalumab and Tremelimumab With or Without High or Low-Dose Radiation Therapy in Treating Patients With Metastatic Colorectal or Non-small Cell Lung Cancer","status":"ACTIVE_NOT_RECRUITING","sponsor":"National Cancer Institute (NCI)","startDate":"2017-08-14","conditions":["Metastatic Colorectal Carcinoma","Metastatic Lung Non-Small Cell Carcinoma","Stage IV Colorectal Cancer AJCC v7","Stage IV Lung Non-Small Cell Cancer AJCC v7","Stage IVA Colorectal Cancer AJCC v7","Stage IVB Colorectal Cancer AJCC v7"],"enrollment":110,"completionDate":"2027-01-02"},{"nctId":"NCT07489976","phase":"PHASE2","title":"IIT2025-03-YANG-LIFT-HCC","status":"RECRUITING","sponsor":"Ju Dong Yang","startDate":"2026-04-01","conditions":["Hepato Cellular Carcinoma"],"enrollment":41,"completionDate":"2030-12-31"},{"nctId":"NCT07288034","phase":"PHASE2","title":"Immunotherapy Biomarkers to Predict First-line PD(L)1-based Immunotherapy Response and Selection of Second-line Treatment in Stage IIIB-IV Non-small Cell Lung Cancer, IMMUNO-BIOMAP Trial","status":"NOT_YET_RECRUITING","sponsor":"City of Hope Medical Center","startDate":"2026-09-21","conditions":["Lung Non-Small Cell Carcinoma","Stage IIIB Lung Cancer AJCC v8","Stage IV Lung Cancer AJCC v8"],"enrollment":535,"completionDate":"2028-09-22"},{"nctId":"NCT02537418","phase":"PHASE1","title":"Durvalumab With or Without Tremelimumab in Advanced Incurable Solid Malignancies Given With or Without Standard Chemotherapy Regimens","status":"ACTIVE_NOT_RECRUITING","sponsor":"Canadian Cancer Trials Group","startDate":"2015-10-16","conditions":["Solid Malignancies"],"enrollment":153,"completionDate":"2026-12-31"},{"nctId":"NCT05063565","phase":"PHASE2","title":"TheraSphere With Durvalumab and Tremelimumab for HCC","status":"ACTIVE_NOT_RECRUITING","sponsor":"Boston Scientific Corporation","startDate":"2023-11-03","conditions":["Hepatocellular Carcinoma"],"enrollment":100,"completionDate":"2027-06"},{"nctId":"NCT03410615","phase":"PHASE2","title":"Cisplatin + Radiotherapy vs Durvalumab + Radiotherapy Followed by Durvalumab vs Durvalumab + Radiotherapy Followed by Tremelimumab + Durvalumab in Intermediate-Risk HPV-Positive Oropharyngeal SCC","status":"ACTIVE_NOT_RECRUITING","sponsor":"Canadian Cancer Trials Group","startDate":"2018-05-28","conditions":["Oropharyngeal Squamous Cell Carcinoma"],"enrollment":129,"completionDate":"2026-07-31"},{"nctId":"NCT03937830","phase":"PHASE2","title":"Combined Treatment of Durvalumab, Bevacizumab, Tremelimumab and Transarterial Chemoembolization (TACE) in Subjects With Hepatocellular Carcinoma or Biliary Tract Carcinoma","status":"ACTIVE_NOT_RECRUITING","sponsor":"National Cancer Institute (NCI)","startDate":"2021-03-10","conditions":["Hepatocellular Cancer","Hepatocellular Carcinoma","Metastatic Hepatocellular Carcinoma"],"enrollment":27,"completionDate":"2027-12-31"},{"nctId":"NCT03298451","phase":"PHASE3","title":"Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma","status":"ACTIVE_NOT_RECRUITING","sponsor":"AstraZeneca","isPivotal":true,"startDate":"2017-10-11","conditions":["Hepatocellular Carcinoma"],"enrollment":1324,"completionDate":"2026-08-27"},{"nctId":"NCT07175441","phase":"PHASE2","title":"Evaluation of RBS2418 in Combination With Tremelimumab Plus Durvalumab in Participants With Advanced Unresectable Hepatocellular Carcinoma","status":"RECRUITING","sponsor":"Riboscience, LLC.","startDate":"2026-04","conditions":["Advanced Unresectable Hepatocellular Carcinoma"],"enrollment":220,"completionDate":"2027-08"},{"nctId":"NCT04499053","phase":"PHASE2","title":"Durvalumab and Tremelimumab in Combination With Chemotherapy in HIV-infected Patients With Non-small Cell Lung Cancer","status":"RECRUITING","sponsor":"Georgetown University","startDate":"2020-12-09","conditions":["Carcinoma, Non-Small Cell Lung"],"enrollment":18,"completionDate":"2027-12"},{"nctId":"NCT06796114","phase":"NA","title":"Identification of Innovative Biomarkers to Predict Outcomes in Hepatocellular Carcinoma Treated With Tremelimumab and Durvalumab","status":"RECRUITING","sponsor":"Centre Hospitalier Universitaire de Besancon","startDate":"2025-06-25","conditions":["Hepatocellular Carcinoma"],"enrollment":120,"completionDate":"2030-01-31"},{"nctId":"NCT03164616","phase":"PHASE3","title":"Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON).","status":"ACTIVE_NOT_RECRUITING","sponsor":"AstraZeneca","isPivotal":true,"startDate":"2017-06-01","conditions":["Non Small Cell Lung Cancer NSCLC"],"enrollment":1186,"completionDate":"2027-11-15"},{"nctId":"NCT07391670","phase":"PHASE1","title":"A Phase I Dose Escalation and Dose Expansion Study to Investigate the Pharmacokinetics and Safety of Subcutaneous Durvalumab","status":"NOT_YET_RECRUITING","sponsor":"AstraZeneca","startDate":"2026-03-31","conditions":["Solid Tumours"],"enrollment":40,"completionDate":"2027-08-30"},{"nctId":"NCT03753919","phase":"PHASE2","title":"Durvalumab Plus Tremelimumab for the Treatment of Patients With Progressive, Refractory Advanced Thyroid Carcinoma -The DUTHY Trial","status":"TERMINATED","sponsor":"Grupo Espanol de Tumores Neuroendocrinos","startDate":"2019-04-02","conditions":["Metastatic Thyroid Papillary Carcinoma","Metastatic Thyroid Follicular Carcinoma","Metastatic Thyroid Cancer"],"enrollment":79,"completionDate":"2024-11-08"},{"nctId":"NCT01843374","phase":"PHASE2","title":"Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Subjects With Unresectable Malignant Mesothelioma","status":"ACTIVE_NOT_RECRUITING","sponsor":"MedImmune LLC","startDate":"2013-05-17","conditions":["Unresectable Pleural or Peritoneal Malignant Mesothelioma"],"enrollment":571,"completionDate":"2026-06-30"},{"nctId":"NCT02812420","phase":"EARLY_PHASE1","title":"Durvalumab and Tremelimumab in Treating Patients With Muscle-Invasive, High-Risk Urothelial Cancer That Cannot Be Treated With Cisplatin-Based Therapy Before Surgery","status":"ACTIVE_NOT_RECRUITING","sponsor":"M.D. Anderson Cancer Center","startDate":"2017-03-07","conditions":["Hydronephrosis","Infiltrating Bladder Urothelial Carcinoma Sarcomatoid Variant","Infiltrating Bladder Urothelial Carcinoma, Micropapillary Variant","Infiltrating Bladder Urothelial Carcinoma, Plasmacytoid Variant","Infiltrating Renal Pelvis Urothelial Carcinoma, Sarcomatoid Variant","Renal Pelvis Urothelial Carcinoma","Stage II Bladder Urothelial Carcinoma AJCC v6 and v7","Stage II Renal Pelvis Cancer AJCC v7","Stage II Ureter Cancer AJCC v7","Stage II Urethral Cancer AJCC v7","Stage III Bladder Urothelial Carcinoma AJCC v6 and v7","Stage III Renal Pelvis Cancer AJCC v7","Stage III Ureter Cancer AJCC v7","Stage III Urethral Cancer AJCC v7","Stage IV Renal Pelvis Cancer AJCC v7","Stage IV Ureter Cancer AJCC v7","Stage IV Urethral Cancer AJCC v7","Ureter Urothelial Carcinoma","Urethral Urothelial Carcinoma"],"enrollment":54,"completionDate":"2027-12-31"},{"nctId":"NCT03057106","phase":"PHASE2","title":"Durvalumab and Tremelimumab ± Platinum-Based Chemotherapy in Patients With Metastatic Squamous or Non-Squamous NSCLC","status":"ACTIVE_NOT_RECRUITING","sponsor":"Canadian Cancer Trials Group","startDate":"2017-03-28","conditions":["Lung Cancer Metastatic"],"enrollment":301,"completionDate":"2026-06-30"},{"nctId":"NCT02453282","phase":"PHASE3","title":"Phase III Open Label First Line Therapy Study of MEDI 4736 (Durvalumab) With or Without Tremelimumab Versus SOC in Non Small-Cell Lung Cancer (NSCLC)","status":"ACTIVE_NOT_RECRUITING","sponsor":"AstraZeneca","startDate":"2015-07-21","conditions":["Non-Small-Cell Lung Carcinoma NSCLC"],"enrollment":1118,"completionDate":"2026-12-31"},{"nctId":"NCT04005690","phase":"EARLY_PHASE1","title":"Targeted Pathway Inhibition in Patients With Pancreatic Cancer","status":"RECRUITING","sponsor":"OHSU Knight Cancer Institute","startDate":"2019-08-01","conditions":["Locally Advanced Pancreatic Ductal Adenocarcinoma","Metastatic Pancreatic Ductal Adenocarcinoma","Stage II Pancreatic Cancer AJCC v8","Stage III Pancreatic Cancer AJCC v8","Stage IV Pancreatic Cancer AJCC v8","Unresectable Pancreatic Ductal Adenocarcinoma","Borderline Resectable Pancreatic Ductal Adenocarcinoma","Resectable Pancreatic Ductal Adenocarcinoma"],"enrollment":90,"completionDate":"2028-02-01"},{"nctId":"NCT06608940","phase":"PHASE1,PHASE2","title":"BC3402 w/ Tremelimumab + Durvalumab (STRIDE) in Hepatocellular Carcinoma","status":"WITHDRAWN","sponsor":"Case Comprehensive Cancer Center","startDate":"2025-11","conditions":["Hepato Cellular Carcinoma (HCC)"],"enrollment":0,"completionDate":"2028-01-01"},{"nctId":"NCT04522544","phase":"PHASE2","title":"Durvalumab and Tremelimumab in Combination With Y-90 SIRT for Intermediate Stage HCC","status":"RECRUITING","sponsor":"Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest","startDate":"2020-12-15","conditions":["Hepatocellular Carcinoma Non-resectable","HCC"],"enrollment":55,"completionDate":"2027-12-31"},{"nctId":"NCT05883644","phase":"PHASE3","title":"Durvalumab and Tremelimumab as First Line Treatment in Participants With Advanced Hepatocellular Carcinoma (HCC)","status":"ACTIVE_NOT_RECRUITING","sponsor":"AstraZeneca","startDate":"2023-06-27","conditions":["Advanced Hepatocellular Carcinoma"],"enrollment":111,"completionDate":"2026-09-30"},{"nctId":"NCT02519348","phase":"PHASE2","title":"A Study of Durvalumab or Tremelimumab Monotherapy, or Durvalumab in Combination With Tremelimumab or Bevacizumab in Advanced Hepatocellular Carcinoma","status":"ACTIVE_NOT_RECRUITING","sponsor":"MedImmune LLC","startDate":"2015-10-19","conditions":["Hepatocellular Carcinoma"],"enrollment":433,"completionDate":"2026-04-01"},{"nctId":"NCT02542293","phase":"PHASE3","title":"Study of Durvalumab With Tremelimumab Versus SoC as 1st Line Therapy in Metastatic Non Small-Cell Lung Cancer (NSCLC) (NEPTUNE)","status":"ACTIVE_NOT_RECRUITING","sponsor":"AstraZeneca","startDate":"2015-11-03","conditions":["Non Small Cell Lung Carcinoma NSCLC"],"enrollment":953,"completionDate":"2026-12-31"},{"nctId":"NCT02499328","phase":"PHASE1,PHASE2","title":"Study to Assess MEDI4736 With Either AZD9150 or AZD5069 in Advanced Solid Tumors & Relapsed Metastatic Squamous Cell Carcinoma of Head & Neck","status":"COMPLETED","sponsor":"AstraZeneca","startDate":"2015-08-06","conditions":["Advanced Solid Tumors & Metastatic Squamous Cell Carcinoma of the Head and Neck"],"enrollment":340,"completionDate":"2025-10-08"},{"nctId":"NCT04395079","phase":"PHASE2","title":"Brachytherapy With Durvalumab or Tremelimumab for the Treatment of Patients With Platinum-Resistant, Refractory, Recurrent, or Metastatic Gynecological Malignancies","status":"ACTIVE_NOT_RECRUITING","sponsor":"Jonsson Comprehensive Cancer Center","startDate":"2020-08-07","conditions":["Metastatic Malignant Female Reproductive System Neoplasm","Platinum-Resistant Malignant Female Reproductive System Neoplasm","Recurrent Malignant Female Reproductive System Neoplasm","Refractory Malignant Female Reproductive System Neoplasm"],"enrollment":9,"completionDate":"2026-12-01"},{"nctId":"NCT03965468","phase":"PHASE2","title":"Immunotherapy, Chemotherapy, Radiotherapy and Surgery for Synchronous Oligo-metastatic NSCLC","status":"ACTIVE_NOT_RECRUITING","sponsor":"ETOP IBCSG Partners Foundation","startDate":"2019-11-19","conditions":["Non-small Cell Lung Cancer","Stage IV","Oligometastasis"],"enrollment":96,"completionDate":"2026-12"},{"nctId":"NCT03682068","phase":"PHASE3","title":"Study of Durvalumab Given With Chemotherapy, Durvalumab in Combination With Tremelimumab Given With Chemotherapy, or Chemotherapy in Patients With Unresectable Urothelial Cancer","status":"ACTIVE_NOT_RECRUITING","sponsor":"AstraZeneca","startDate":"2018-09-27","conditions":["Unresectable Locally Advanced Urothelial Cancer","Metastatic Urothelial Cancer"],"enrollment":1246,"completionDate":"2026-04-29"},{"nctId":"NCT06904170","phase":"PHASE2,PHASE3","title":"Durvalumab and Tremelimumab With or Without Hepatic Arterial Infusion of Chemotherapy in Hepatocellular Carcinoma","status":"RECRUITING","sponsor":"UNICANCER","startDate":"2025-11-14","conditions":["Hepatocellular Carcinoma"],"enrollment":196,"completionDate":"2030-09"},{"nctId":"NCT06824363","phase":"EARLY_PHASE1","title":"ProofPrincip IntraTu TCells SinglDoseImmunCheckpoinInhib Gastro-Esophage Adenocarcinoma w/ARID1a Mu","status":"NOT_YET_RECRUITING","sponsor":"University of California, Irvine","startDate":"2026-04","conditions":["Solid Tumor, Adult","Malignant Solid Tumor","Stomach Adenocarcinoma","Esophageal Adenocarcinoma"],"enrollment":34,"completionDate":"2028-07"},{"nctId":"NCT02516241","phase":"PHASE3","title":"Study of MEDI4736 (Durvalumab) With or Without Tremelimumab Versus Standard of Care Chemotherapy in Urothelial Cancer","status":"ACTIVE_NOT_RECRUITING","sponsor":"AstraZeneca","startDate":"2015-11-02","conditions":["Urothelial Cancer"],"enrollment":1126,"completionDate":"2026-12-31"},{"nctId":"NCT07174570","phase":"PHASE2","title":"Celecoxib, Durvalumab and Tremelimumab for the Treatment of Patients With Advanced or Metastatic Liver Cancer","status":"RECRUITING","sponsor":"Emory University","startDate":"2026-01-02","conditions":["Advanced Hepatocellular Carcinoma","Metastatic Hepatocellular Carcinoma","Stage III Hepatocellular Carcinoma AJCC v8","Stage IV Hepatocellular Carcinoma AJCC v8"],"enrollment":39,"completionDate":"2027-11-13"},{"nctId":"NCT03158064","phase":"PHASE2","title":"Evaluating Immune Therapy, Duravalumab (MEDI4736) With Tremelimumab for Relapsed/Refractory Germ Cell Tumors","status":"ACTIVE_NOT_RECRUITING","sponsor":"Memorial Sloan Kettering Cancer Center","startDate":"2017-05-15","conditions":["Germ Cell Tumor","Nonseminomatous Germ Cell Tumor","Seminoma","Germinomatous Germ Cell Tumor","Dysgerminoma","Pineal Germ Cell Tumor"],"enrollment":30,"completionDate":"2026-11"},{"nctId":"NCT05154994","phase":"PHASE1","title":"Tremelimumab + Durvalumab(MEDI4736)+ Belinostat in Urothelial Carcinoma","status":"ACTIVE_NOT_RECRUITING","sponsor":"University of Utah","startDate":"2022-01-14","conditions":["Infiltrating Urothelial Carcinoma, Sarcomatoid Variant","Locally Advanced Urothelial Carcinoma","Metastatic Urothelial Carcinoma","Unresectable Urothelial Carcinoma"],"enrollment":9,"completionDate":"2027-11-30"},{"nctId":"NCT03539822","phase":"PHASE1,PHASE2","title":"Cabozantinib Plus Durvalumab With or Without Tremelimumab in Patients With Gastroesophageal Cancer and Other Gastrointestinal Malignancies","status":"RECRUITING","sponsor":"Anwaar Saeed","startDate":"2018-10-22","conditions":["Gastric Cancer","Esophageal Adenocarcinoma","Hepatocellular Carcinoma","Colorectal Cancer"],"enrollment":117,"completionDate":"2029-06-30"},{"nctId":"NCT07166406","phase":"PHASE3","title":"Testing Immunotherapy With or Without Stereotactic Body Radiation Therapy in Patients With Advanced Liver Cancer, HELIO-RT Trial","status":"RECRUITING","sponsor":"NRG Oncology","startDate":"2025-10-07","conditions":["Advanced Hepatocellular Carcinoma","Stage III Hepatocellular Carcinoma AJCC v8","Stage IV Hepatocellular Carcinoma AJCC v8"],"enrollment":252,"completionDate":"2029-03-10"},{"nctId":"NCT06855225","phase":"PHASE2","title":"A Phase II Study of Single Tremelimumab With Regular Interval Durvalumab Plus Gemcitabine and Cisplatin in Locally Advanced Unresectable/Metastatic Combined Hepatocellular-cholangiocarcinoma","status":"NOT_YET_RECRUITING","sponsor":"Mehmet Akce","startDate":"2026-03","conditions":["Combined Hepatocellular and Cholangiocarcinoma"],"enrollment":29,"completionDate":"2027-04"},{"nctId":"NCT06921785","phase":"PHASE3","title":"Phase III Study of Rilvegostomig in Combination With Bevacizumab With or Without Tremelimumab as First-line Treatment of Hepatocellular Carcinoma","status":"RECRUITING","sponsor":"AstraZeneca","startDate":"2025-05-06","conditions":["Hepatocellular Carcinoma"],"enrollment":1220,"completionDate":"2030-03-14"},{"nctId":"NCT03075527","phase":"PHASE2","title":"A Phase 2 Study of Durvalumab in Combination With Tremelimumab in Malignant Pleural Mesothelioma","status":"TERMINATED","sponsor":"Dana-Farber Cancer Institute","startDate":"2017-04-10","conditions":["Mesothelioma"],"enrollment":19,"completionDate":"2024-12-16"},{"nctId":"NCT03923270","phase":"PHASE1","title":"Radiotherapy and Durvalumab/Durvalumab Combo (Tremelimumab/Olaparid) for Small Cell Lung Cancer","status":"ACTIVE_NOT_RECRUITING","sponsor":"H. Lee Moffitt Cancer Center and Research Institute","startDate":"2019-06-06","conditions":["Small Cell Lung Cancer Extensive Stage","Small-cell Lung Cancer"],"enrollment":25,"completionDate":"2026-12"},{"nctId":"NCT06526104","phase":"PHASE2","title":"Study of Tremelimumab and Durvalumab (MEDI4736) (T300+D) in Advanced Hepatocellular Carcinomas With Child-Pugh-B Cirrhosis","status":"RECRUITING","sponsor":"The University of Texas Health Science Center at San Antonio","startDate":"2024-12-02","conditions":["Hepatocellular Carcinoma","Cirrhosis, Liver"],"enrollment":32,"completionDate":"2027-12-01"},{"nctId":"NCT07081633","phase":"PHASE2","title":"Durvalumab and Tremelimumab With Lenvatinib as First-line Treatment in Patients With Unresectable Hepatocellular Carcinoma","status":"RECRUITING","sponsor":"AstraZeneca","startDate":"2025-08-05","conditions":["Hepatocellular Carcinoma"],"enrollment":114,"completionDate":"2028-12-31"},{"nctId":"NCT07307456","phase":"PHASE2","title":"Tremelimumab Combined With BCG Perfusion for the Treatment of HR-NMIBC After TURBT Surgery Exploration","status":"RECRUITING","sponsor":"Changhai Hospital","startDate":"2025-12-08","conditions":["Bladder Cancer"],"enrollment":31,"completionDate":"2028-12-08"},{"nctId":"NCT05380713","phase":"PHASE2","title":"......SMARTEST Trial......","status":"COMPLETED","sponsor":"University Health Network, Toronto","startDate":"2022-05-03","conditions":["Mesothelioma, Malignant"],"enrollment":30,"completionDate":"2025-12-20"},{"nctId":"NCT06252753","phase":"","title":"Observational Study Protocol: LIVER-R","status":"RECRUITING","sponsor":"AstraZeneca","startDate":"2023-03-16","conditions":["Hepatobiliary Cancers"],"enrollment":4490,"completionDate":"2030-12-30"},{"nctId":"NCT04960709","phase":"PHASE3","title":"Treatment Combination of Durvalumab, Tremelimumab and Enfortumab Vedotin or Durvalumab and Enfortumab Vedotin in Patients With Muscle Invasive Bladder Cancer Ineligible to Cisplatin or Who Refuse Cisplatin","status":"ACTIVE_NOT_RECRUITING","sponsor":"AstraZeneca","startDate":"2021-08-05","conditions":["Muscle Invasive Bladder Cancer"],"enrollment":712,"completionDate":"2028-09-08"},{"nctId":"NCT06880523","phase":"PHASE2","title":"STRIDE (Durvalumab + Tremelimumab) With Lenvatinib vs STRIDE Alone in Unresectable Hepatocellular Carcinoma","status":"RECRUITING","sponsor":"Canadian Cancer Trials Group","startDate":"2025-10-21","conditions":["Hepatocellular Carcinoma"],"enrollment":140,"completionDate":"2028-12-31"},{"nctId":"NCT04430452","phase":"PHASE2","title":"Durvalumab With/Without Tremelimumab After Palliative Hypofractionated Radiotherapy for Hepatocellular Carcinoma","status":"RECRUITING","sponsor":"Mary Feng, MD","startDate":"2022-02-04","conditions":["Advanced Hepatocellular Carcinoma","Stage III Hepatocellular Carcinoma AJCC v8","Stage IIIA Hepatocellular Carcinoma AJCC v8","Stage IIIB Hepatocellular Carcinoma AJCC v8","Stage IV Hepatocellular Carcinoma AJCC v8","Stage IVA Hepatocellular Carcinoma AJCC v8","Stage IVB Hepatocellular Carcinoma AJCC v8"],"enrollment":21,"completionDate":"2029-07-31"},{"nctId":"NCT04238637","phase":"PHASE2","title":"Immunotherapy Combined With Y-90 SIRT Therapy in Advanced Stage Intrahepatic Biliary Tract Cancer (BTC)","status":"ACTIVE_NOT_RECRUITING","sponsor":"Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest","startDate":"2019-11-01","conditions":["Intrahepatic Cholangiocarcinoma"],"enrollment":50,"completionDate":"2027-12"},{"nctId":"NCT06564623","phase":"PHASE1","title":"Targeting Driver Oncogenes With a Peptide Vaccine Plus Durvalumab and Tremelimumab for Patients With Biliary Tract Cancers (BTC)","status":"RECRUITING","sponsor":"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins","startDate":"2025-05-27","conditions":["Biliary Tract Cancers"],"enrollment":25,"completionDate":"2029-05"},{"nctId":"NCT03249142","phase":"PHASE1,PHASE2","title":"Immunotherapy With Neo-adjuvant Chemotherapy for OVarian Cancer","status":"COMPLETED","sponsor":"ARCAGY/ GINECO GROUP","startDate":"2017-10-18","conditions":["Ovarian Cancer"],"enrollment":69,"completionDate":"2024-12-31"},{"nctId":"NCT02639026","phase":"PHASE1","title":"Trial Of Hypofractionated Radiotherapy In Combination With MEDI4736 And Tremelimumab For Patients With Metastatic Melanoma And Lung, Breast And Pancreatic Cancers","status":"COMPLETED","sponsor":"Abramson Cancer Center at Penn Medicine","startDate":"2016-01-26","conditions":["Metastatic","Melanoma","Non Small Cell Lung Cancer (NSCLC)","Breast Cancer","Pancreatic Cancer"],"enrollment":53,"completionDate":"2023-06-27"},{"nctId":"NCT03703297","phase":"PHASE3","title":"Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy","status":"ACTIVE_NOT_RECRUITING","sponsor":"AstraZeneca","startDate":"2018-09-27","conditions":["Small Cell Lung Cancer"],"enrollment":730,"completionDate":"2026-10-23"},{"nctId":"NCT06994299","phase":"PHASE2","title":"A Pilot Trial of Preoperative Irradiation With the STRIDE (Single Dose of Tremelimumab With Ongoing Durvalumab) Regimen (PRISM) for Resectable/Advanced Hepatocellular Carcinoma","status":"WITHDRAWN","sponsor":"Weill Medical College of Cornell University","startDate":"2025-10-01","conditions":["Hepatocellular Carcinoma (HCC)"],"enrollment":0,"completionDate":"2028-07-01"},{"nctId":"NCT06117891","phase":"","title":"An Observational Study to Learn More About How Well a Treatment Works When Given After Treatment With Atezolizumab and Bevacizumab or Another Similar Combination of Drugs in Adults With Liver Cancer That Cannot be Treated With Surgery","status":"RECRUITING","sponsor":"Bayer","startDate":"2023-11-27","conditions":["Unresectable Hepatocellular Carcinoma"],"enrollment":300,"completionDate":"2027-02-01"},{"nctId":"NCT03911557","phase":"PHASE2","title":"Durvalumab and Tremelimumab Combination in Somatically Hypermutated Recurrent Solid Tumors","status":"COMPLETED","sponsor":"John L. Villano, MD, PhD","startDate":"2019-06-08","conditions":["Tumor, Solid"],"enrollment":14,"completionDate":"2025-10-10"},{"nctId":"NCT07226063","phase":"PHASE2","title":"Maintenance Zanzalintinib and Durvalumab in Participants With Advanced Hepatocellular Cancer","status":"NOT_YET_RECRUITING","sponsor":"Amit Mahipal","startDate":"2026-02","conditions":["Hepatocellular Carcinoma","Liver Cancer"],"enrollment":16,"completionDate":"2027-08"},{"nctId":"NCT06698250","phase":"PHASE2","title":"Zanzalintinib (XL-092) Plus Durvalumab and Tremelimumab in Unresectable Hepatocellular Carcinoma (ZENOBIA)","status":"RECRUITING","sponsor":"Anwaar Saeed","startDate":"2024-12-18","conditions":["Hepatocellular Carcinoma"],"enrollment":40,"completionDate":"2027-04-30"},{"nctId":"NCT03581487","phase":"PHASE1,PHASE2","title":"Durvalumab, Tremelimumab, and Selumetinib in Treating Participants With Recurrent or Stage IV Non-small Cell Lung Cancer","status":"COMPLETED","sponsor":"M.D. Anderson Cancer Center","startDate":"2019-04-01","conditions":["Recurrent Lung Non-Small Cell Carcinoma","Stage IV Lung Cancer AJCC v8","Stage IVA Lung Cancer AJCC v8","Stage IVB Lung Cancer AJCC v8"],"enrollment":40,"completionDate":"2025-10-30"},{"nctId":"NCT03043872","phase":"PHASE3","title":"Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (CASPIAN)","status":"ACTIVE_NOT_RECRUITING","sponsor":"AstraZeneca","startDate":"2017-03-27","conditions":["Small Cell Lung Carcinoma Extensive Disease"],"enrollment":987,"completionDate":"2025-12-31"},{"nctId":"NCT06058663","phase":"PHASE1","title":"Radioembolization With Tremelimumab and Durvalumab for Locally Advanced Unresectable or Oligo-Metastatic Intrahepatic Cholangiocarcinoma","status":"RECRUITING","sponsor":"Mayo Clinic","startDate":"2024-06-06","conditions":["Locally Advanced Intrahepatic Cholangiocarcinoma","Oligometastatic Intrahepatic Cholangiocarcinoma","Stage III Intrahepatic Cholangiocarcinoma AJCC v8","Stage IV Intrahepatic Cholangiocarcinoma AJCC v8","Unresectable Intrahepatic Cholangiocarcinoma"],"enrollment":16,"completionDate":"2028-11-30"},{"nctId":"NCT03237377","phase":"PHASE2","title":"Neoadjuvant Immunoradiation for Resectable Non-Small Cell Lung Cancer","status":"TERMINATED","sponsor":"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins","startDate":"2017-12-12","conditions":["Non-Small Cell Lung Cancer"],"enrollment":9,"completionDate":"2024-05-23"},{"nctId":"NCT05932199","phase":"PHASE1,PHASE2","title":"Neoadjuvant Durvalumab and Tremelimumab With and Without Chemotherapy for Mesothelioma","status":"RECRUITING","sponsor":"Baylor College of Medicine","startDate":"2024-07-03","conditions":["Mesothelioma"],"enrollment":52,"completionDate":"2028-05-31"},{"nctId":"NCT02938793","phase":"PHASE2","title":"Durvalumab in Combination With Tremelimumab in Subjects With Advanced Rare Solid Tumors","status":"TERMINATED","sponsor":"Prisma Health-Upstate","startDate":"2016-12-01","conditions":["Cancer","Rare Disease"],"enrollment":92,"completionDate":"2025-09-17"},{"nctId":"NCT03026062","phase":"PHASE2","title":"Durvalumab and Tremelimumab in Treating Participants With Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer","status":"COMPLETED","sponsor":"M.D. Anderson Cancer Center","startDate":"2017-05-18","conditions":["Platinum-Resistant Fallopian Tube Carcinoma","Platinum-Resistant Ovarian Carcinoma","Platinum-Resistant Primary Peritoneal Carcinoma","Recurrent Fallopian Tube Carcinoma","Recurrent Ovarian Carcinoma","Recurrent Primary Peritoneal Carcinoma","Refractory Fallopian Tube Carcinoma","Refractory Ovarian Carcinoma","Refractory Primary Peritoneal Carcinoma"],"enrollment":100,"completionDate":"2025-09-11"},{"nctId":"NCT03019003","phase":"PHASE1","title":"Oral Decitabine (ASTX727) and Durvalumab in Recurrent and/or Metastatic Head and Neck Cancer Patients","status":"COMPLETED","sponsor":"Massachusetts General Hospital","startDate":"2017-03-20","conditions":["Head and Neck Cancer"],"enrollment":13,"completionDate":"2024-09-24"},{"nctId":"NCT06840782","phase":"PHASE3","title":"First-line Immunotherapy-based Standard of Care and Local Ablative Treatments for Oligometastatic Non-small Cell Lung Cancer Patients.","status":"RECRUITING","sponsor":"Gustave Roussy, Cancer Campus, Grand Paris","startDate":"2025-09-09","conditions":["Oligometastatic Non-small Cell Lung Cancer (NSCLC)"],"enrollment":124,"completionDate":"2030-02"},{"nctId":"NCT07168668","phase":"PHASE2","title":"Partial Immune-boost TACE in unrEseCTable HCC Patients Under Systemic Treatment","status":"NOT_YET_RECRUITING","sponsor":"Chang Gung Memorial Hospital","startDate":"2025-09-15","conditions":["HCC","Tace","Immunotherapy"],"enrollment":90,"completionDate":"2028-05-30"},{"nctId":"NCT04605731","phase":"PHASE1","title":"Durvalumab and Tremelimumab After Radioembolization for the Treatment of Unresectable, Locally Advanced Liver Cancer","status":"ACTIVE_NOT_RECRUITING","sponsor":"City of Hope Medical Center","startDate":"2021-08-03","conditions":["BCLC Stage B Hepatocellular Carcinoma","BCLC Stage C Hepatocellular Carcinoma","Locally Advanced Hepatocellular Carcinoma","Stage III Hepatocellular Carcinoma AJCC v8","Stage IIIA Hepatocellular Carcinoma AJCC v8","Stage IIIB Hepatocellular Carcinoma AJCC v8","Stage IV Hepatocellular Carcinoma AJCC v8","Stage IVA Hepatocellular Carcinoma AJCC v8","Stage IVB Hepatocellular Carcinoma AJCC v8","Unresectable Hepatocellular Carcinoma"],"enrollment":25,"completionDate":"2026-02-25"},{"nctId":"NCT06999694","phase":"PHASE2","title":"Proton Radiotherapy Plus Tremelimumab/Durvalumab for BCLC Stage B and C HCC","status":"RECRUITING","sponsor":"Chang Gung Memorial Hospital","startDate":"2025-05-22","conditions":["HCC - Hepatocellular Carcinoma","Durvalumab","Tremelimumab","Proton Radiotherapy"],"enrollment":45,"completionDate":"2033-05-31"},{"nctId":"NCT02962063","phase":"PHASE1,PHASE2","title":"Durvalumab, an Anti-PDLI Antibody, and Tremelimumab, an Anti-CTLA4 Antibody, and Chemoradiation Before Surgery for Esophageal Cancer","status":"ACTIVE_NOT_RECRUITING","sponsor":"Memorial Sloan Kettering Cancer Center","startDate":"2016-11","conditions":["Esophageal Adenocarcinoma","Gastroesophageal Junction Adenocarcinoma"],"enrollment":64,"completionDate":"2026-11"},{"nctId":"NCT05701488","phase":"PHASE1","title":"SIRT With Tremelimumab and Durvalumab for Resectable HCC","status":"RECRUITING","sponsor":"Jiping Wang, MD, PhD","startDate":"2023-04-21","conditions":["Resectable Hepatocellular Carcinoma","Hepatocellular Carcinoma","Hepatocellular Cancer"],"enrollment":20,"completionDate":"2026-10-01"},{"nctId":"NCT03385655","phase":"PHASE2","title":"Prostate Cancer Biomarker Enrichment and Treatment Selection","status":"ACTIVE_NOT_RECRUITING","sponsor":"Canadian Cancer Trials Group","startDate":"2018-08-01","conditions":["Prostate Cancer"],"enrollment":200,"completionDate":"2025-12-31"},{"nctId":"NCT03638141","phase":"PHASE2","title":"CTLA-4 /PD-L1 Blockade Following Transarterial Chemoembolization (DEB-TACE) in Patients With Intermediate Stage of HCC (Hepatocellular Carcinoma) Using Durvalumab and Tremelimumab","status":"COMPLETED","sponsor":"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins","startDate":"2019-10-02","conditions":["Intermediate Stage of Hepatocellular Carcinoma","Hepatocellular Carcinoma"],"enrollment":21,"completionDate":"2024-08-20"},{"nctId":"NCT06109272","phase":"PHASE2,PHASE3","title":"A Study to Assess the Dose, Adverse Events, and Change in Disease Activity of Livmoniplimab as an Intravenous (IV) Solution in Combination With Budigalimab as an IV Solution in Adult Participants With Hepatocellular Carcinoma (HCC)","status":"RECRUITING","sponsor":"AbbVie","startDate":"2024-01-11","conditions":["Hepatocellular Carcinoma"],"enrollment":660,"completionDate":"2030-09"},{"nctId":"NCT07122089","phase":"PHASE2","title":"Evaluation of SIRT Followed by Immunotherapy for Treatment of Hepatocellular Carcinoma With Portal Vein Thrombosis","status":"NOT_YET_RECRUITING","sponsor":"Center Eugene Marquis","startDate":"2026-01-02","conditions":["Hepatocellular Carcinoma Non-resectable"],"enrollment":80,"completionDate":"2030-01-02"},{"nctId":"NCT02029001","phase":"PHASE2","title":"Adapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatment","status":"RECRUITING","sponsor":"Centre Leon Berard","startDate":"2014-03","conditions":["Malignant Solid Neoplasms"],"enrollment":900,"completionDate":"2027-10"},{"nctId":"NCT06841172","phase":"PHASE3","title":"Continuation of First-line Therapy With Radiotherapy Versus Early Switch to Second-line Therapy in Oligoprogressive HCC","status":"RECRUITING","sponsor":"Shandong Cancer Hospital and Institute","startDate":"2025-07-21","conditions":["OligoProgressive Metastatic Disease","Hepatocellular Carcinoma (HCC)","Radiotherapy","Systemic Therapy"],"enrollment":132,"completionDate":"2028-07-01"},{"nctId":"NCT03267589","phase":"PHASE2","title":"Trial in Patients With Relapsed Ovarian Cancer","status":"COMPLETED","sponsor":"Nordic Society of Gynaecological Oncology - Clinical Trials Unit","startDate":"2018-05-14","conditions":["Ovarian Cancer"],"enrollment":25,"completionDate":"2021-10-19"},{"nctId":"NCT03704480","phase":"PHASE2","title":"Durvalumab + Tremelimumab ± Paclitaxel in Advanced BTC After Platinum Chemotherapy.","status":"ACTIVE_NOT_RECRUITING","sponsor":"GERCOR - Multidisciplinary Oncology Cooperative Group","startDate":"2018-11-09","conditions":["Advanced Biliary Tract Carcinoma"],"enrollment":106,"completionDate":"2025-12-31"},{"nctId":"NCT05451043","phase":"PHASE2","title":"Durvalumab and Tremelimumab in Combination With Propranolol and Chemotherapy for Treatment of Advanced Hepatopancreabiliary Tumors (BLOCKED)","status":"RECRUITING","sponsor":"AHS Cancer Control Alberta","startDate":"2023-07-05","conditions":["Pancreatic Cancer","Hepatocellular Cancer","Biliary Tract Cancer","Cholangiocarcinoma"],"enrollment":62,"completionDate":"2029-10-01"},{"nctId":"NCT07027436","phase":"PHASE3","title":"Radiation Therapy Followed by Durvalumab (MEDI4736) and Tremelimumab And Surgery Versus Radiation Therapy Followed by Surgery for Resectable Hepatocellular Carcinoma.","status":"NOT_YET_RECRUITING","sponsor":"Hamilton Health Sciences Corporation","startDate":"2025-07-07","conditions":["Hepatocellular Carcinoma (HCC)"],"enrollment":30,"completionDate":"2028-10-10"},{"nctId":"NCT02815995","phase":"PHASE2","title":"Multi-Arm Study to Test the Efficacy of Immunotherapeutic Agents in Multiple Sarcoma Subtypes","status":"COMPLETED","sponsor":"M.D. Anderson Cancer Center","startDate":"2016-08-16","conditions":["Advanced and/or Metastatic Sarcoma"],"enrollment":57,"completionDate":"2024-06-17"},{"nctId":"NCT03847649","phase":"PHASE2","title":"A Phase II Study of Durvalumab Treatment - Substudy A: In Patients Who Discontinued Prior Checkpoint Therapy Due to Immune Related Toxicity - Substudy B: For Continued Treatment (+/- Tremelimumab) of Patients Previously Enrolled to Completed CCTG Studies","status":"RECRUITING","sponsor":"Canadian Cancer Trials Group","startDate":"2020-03-09","conditions":["Cancer"],"enrollment":60,"completionDate":"2031-04-30"},{"nctId":"NCT04817826","phase":"PHASE2","title":"TremelImumab aNd Durvalumab For the Non-operatIve Management (NOM) of MSI-high Resectable GC/GEJC.","status":"ACTIVE_NOT_RECRUITING","sponsor":"Gruppo Oncologico del Nord-Ovest","startDate":"2021-04-01","conditions":["Gastric Cancer","Microsatellite Instability"],"enrollment":31,"completionDate":"2026-04-30"},{"nctId":"NCT06999707","phase":"PHASE2","title":"Photon Radiotherapy Plus Tremelimumab/Durvalumab for BCLC Stage B and C HCC","status":"RECRUITING","sponsor":"Chang Gung Memorial Hospital","startDate":"2025-05-22","conditions":["HCC - Hepatocellular Carcinoma","Tremelimumab","Durvalumab","Radiotherapy"],"enrollment":45,"completionDate":"2033-05-31"},{"nctId":"NCT03277482","phase":"PHASE1","title":"Durvalumab, Tremelimumab + Radiotherapy in Gynecologic Cancer","status":"TERMINATED","sponsor":"Dana-Farber Cancer Institute","startDate":"2018-06-01","conditions":["Recurrent Gynecological Cancer","Metastatic Cervical Cancer","Metastatic Ovarian Cancer","Metastatic Vaginal Cancer","Metastatic Vulvar Cancer","Metastatic Endometrial Cancer","Recurrent Cervical Carcinoma","Recurrent Ovarian Carcinoma","Recurrent Vaginal Cancer","Recurrent Vulvar Cancer","Recurrent Endometrial Cancer"],"enrollment":16,"completionDate":"2022-07-15"},{"nctId":"NCT02571725","phase":"PHASE1,PHASE2","title":"PARP-inhibition and CTLA-4 Blockade in BRCA-deficient Ovarian Cancer","status":"ACTIVE_NOT_RECRUITING","sponsor":"New Mexico Cancer Research Alliance","startDate":"2016-02-23","conditions":["Ovarian Cancer","Fallopian Tube Cancer","Peritoneal Neoplasms"],"enrollment":50,"completionDate":"2027-07-15"},{"nctId":"NCT02788773","phase":"PHASE2","title":"Durvalumab With or Without Tremelimumab in Metastatic Castration Resistant Prostate Cancer","status":"COMPLETED","sponsor":"Canadian Cancer Trials Group","startDate":"2016-12-15","conditions":["Prostate Cancer"],"enrollment":52,"completionDate":"2025-05-01"},{"nctId":"NCT06911255","phase":"PHASE1,PHASE2","title":"Safety and Efficacy of Tremelimumab+Durvalumab(MEDI4736)+TACE in Unresectable Hepatocellular Carcinoma","status":"RECRUITING","sponsor":"Yoon Jun Kim","startDate":"2025-04-18","conditions":["Hepatocellular Carcinoma (HCC)","Unresectable Hepatocellular Carcinoma"],"enrollment":24,"completionDate":"2028-06-30"},{"nctId":"NCT03212469","phase":"PHASE1,PHASE2","title":"A Trial of Durvalumab and Tremelimumab in Combination With SBRT in Patients With Metastatic Cancer","status":"COMPLETED","sponsor":"Gustave Roussy, Cancer Campus, Grand Paris","startDate":"2017-06-20","conditions":["Head and Neck Squamous Cell Carcinoma","Lung Cancer","Oesophageal Cancer"],"enrollment":54,"completionDate":"2025-02-24"},{"nctId":"NCT04585490","phase":"PHASE3","title":"Personalized Escalation of Consolidation Treatment Following Chemoradiotherapy and Immunotherapy in Stage III NSCLC in Stage III NSCLC","status":"RECRUITING","sponsor":"Maximilian Diehn","startDate":"2021-08-25","conditions":["Non Small Cell Lung Cancer","NSCLC, Stage III","Nsclc"],"enrollment":48,"completionDate":"2028-04-01"},{"nctId":"NCT05239169","phase":"PHASE2","title":"Immunotherapy With Durva and Treme With or Without Capecitabine in Adjuvant Treatment for Biliary Tract Cancer","status":"COMPLETED","sponsor":"Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest","startDate":"2022-05-23","conditions":["Biliary Tract Cancer (CCA)","Intrahepatic Cholangiocarcinoma","Hilar Cholangiocarcinoma","Distal Cholangiocarcinoma","Gall Bladder Carcinoma"],"enrollment":40,"completionDate":"2025-02-20"},{"nctId":"NCT03601455","phase":"PHASE2","title":"Radiation Therapy and Durvalumab With or Without Tremelimumab in Treating Participants With Unresectable, Locally Advanced, or Metastatic Bladder Cancer","status":"ACTIVE_NOT_RECRUITING","sponsor":"Jonsson Comprehensive Cancer Center","startDate":"2018-10-26","conditions":["Bladder Urothelial Carcinoma","Stage IV Bladder Cancer AJCC v8","Stage IVA Bladder Cancer AJCC v8","Stage IVB Bladder Cancer AJCC v8"],"enrollment":13,"completionDate":"2027-01-31"},{"nctId":"NCT06045975","phase":"PHASE2","title":"Durvalumab/Tremelimumab in Neoadjuvant and Adjuvant Setting in Patients With HCC Treated by by Percutaneous Ablation Procedure","status":"RECRUITING","sponsor":"Assistance Publique - Hôpitaux de Paris","startDate":"2024-03-28","conditions":["HCC - Hepatocellular Carcinoma"],"enrollment":30,"completionDate":"2028-09-28"},{"nctId":"NCT02879318","phase":"PHASE2","title":"Gemcitabine and Nab-Paclitaxel vs Gemcitabine, Nab-Paclitaxel, Durvalumab and Tremelimumab as 1st Line Therapy in Metastatic Pancreatic Adenocarcinoma","status":"COMPLETED","sponsor":"Canadian Cancer Trials Group","startDate":"2016-11-07","conditions":["Pancreatic Adenocarcinoma"],"enrollment":180,"completionDate":"2025-03-14"}],"_emaApprovals":[{"date":"2023-02-20","status":"Authorised","company":"ASTRAZENECA AB"}],"genericFilers":[],"latestUpdates":[],"manufacturing":[],"pivotalTrials":["NCT03298451","NCT03164616"],"administration":{"route":"Intravenous","formulation":"Injection","formulations":[{"form":"INJECTION, SOLUTION","route":"INTRAVENOUS","productName":"IMJUDO"}]},"_patentsChecked":true,"crossReferences":{"MMSL":"362315","NDDF":"019215","UNII":"QEN1X95CIX","VANDF":"4041790","INN_ID":"8716","RXNORM":"2619312","UMLSCUI":"C2351038","chemblId":"CHEMBL2108658","ChEMBL_ID":"CHEMBL2108658","KEGG_DRUG":"D06657","DRUGBANK_ID":"DB11771","IUPHAR_LIGAND_ID":"8462","MESH_SUPPLEMENTAL_RECORD_UI":"C520704"},"formularyStatus":[],"originalProduct":{"form":"INJECTION, SOLUTION","route":"INTRAVENOUS","company":"AstraZeneca Pharmaceuticals LP","brandName":"IMJUDO","isOriginal":true,"marketingStatus":"BLA"},"_enricherVersion":"v2","developmentCodes":[],"ownershipHistory":[{"period":"2022-","companyName":"AstraZeneca","relationship":"Original Developer"},{"period":"2023","companyName":"AstraZeneca K.K.","relationship":"PMDA Licensee"}],"publicationCount":807,"therapeuticAreas":["Oncology"],"_revenueScrapedAt":"2026-04-08 13:57:45.719459+00","atcClassification":{"source":"DrugCentral","atcCode":"L01FX20","allCodes":["L01FX20"]},"biosimilarFilings":[],"originalDeveloper":"Astrazeneca Ab","recentPublications":[{"date":"2026 Feb 5","pmid":"41904890","title":"MVI-targeted carbon-ion radiotherapy combined with immunotherapy for advanced hepatocellular carcinoma: Phase Ib DEPARTURE trial.","journal":"JHEP reports : innovation in hepatology"},{"date":"2026 Mar 25","pmid":"41876974","title":"The effect of prior transarterial chemoembolization on response to immune checkpoint inhibitor treatment in patients with hepatocellular carcinoma.","journal":"Clinical and molecular hepatology"},{"date":"2026 Mar 23","pmid":"41870699","title":"A case of a patient with advanced HCC with Vp4 on hemodialysis who responded to a multimodality treatment including hepatic arterial infusion, radiation therapy, immunotherapy, and molecular-targeted drugs.","journal":"Clinical journal of gastroenterology"},{"date":"2026 Mar 17","pmid":"41850829","title":"Favorable Response to Chemotherapy with Durvalumab plus Tremelimumab in Two Cases of KRAS G12C-Positive Pulmonary Sarcomatoid Carcinoma: A Case Report.","journal":"Internal medicine (Tokyo, Japan)"},{"date":"2026 Mar 12","pmid":"41814915","title":"Impact of Borderline Resectable Criteria on Hepatocellular Carcinoma Treatment From the Perspective of Tumor Burden.","journal":"World journal of surgery"}],"companionDiagnostics":[],"genericManufacturerList":[],"status":"approved","companyName":"AstraZeneca","companyId":"astrazeneca","modality":"Monoclonal antibody","firstApprovalDate":"2022","aiSummary":"","enrichmentLevel":4,"visitCount":0,"regulatoryByCountry":[{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2022-10-21T00:00:00.000Z","mah":"ASTRAZENECA AB","brand_name_local":null,"application_number":""},{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2023-06-14T00:00:00.000Z","mah":"ASTRAZENECA AB","brand_name_local":null,"application_number":"BLA761289"},{"country_code":"JP","regulator":"PMDA","status":"approved","approval_date":"2023-12-23T00:00:00.000Z","mah":"AstraZeneca K.K.","brand_name_local":null,"application_number":""},{"country_code":"IL","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"IL","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"SG","regulator":"HSA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"SG","regulator":"HSA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AE","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AE","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"KR","regulator":"MFDS","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"KR","regulator":"MFDS","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AU","regulator":"TGA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AU","regulator":"TGA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"GB","regulator":"MHRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"GB","regulator":"MHRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"EU","regulator":"EMA","status":"pending","approval_date":null,"mah":"","brand_name_local":"","application_number":""},{"country_code":"CA","regulator":"Health Canada","status":"approved","approval_date":null,"mah":"","brand_name_local":"","application_number":""}],"trialStats":{"total":53,"withResults":17},"validation":{"fieldsValidated":1,"lastValidatedAt":"2026-04-20T02:04:45.647691+00:00","fieldsConflicting":6,"overallConfidence":0.8},"verificationStatus":"verified","dataCompleteness":{"mechanism":true,"indications":true,"safety":true,"trials":true,"score":4}}