NCT02864251: CheckMate722

A Study of Nivolumab + Chemotherapy or Nivolumab + Ipilimumab Versus Chemotherapy in Non-Small Cell Lung Cancer (NSCLC) Participants With Epidermal Growth Factor Receptor (EGFR) Mutation Who Failed 1L or 2L EGFR Tyrosine Kinase Inhibitor (TKI) Therapy

Completed Phase 3 Results posted Last updated 28 September 2023

What this trial tests

Phase 3 trial testing Nivolumab in Non-Small-Cell Lung Carcinoma in 367 participants. Completed in 17 October 2022.

Timeline

17 March 2017

Primary endpoint
20 January 2022

17 October 2022

Quick facts

Lead sponsor	Bristol-Myers Squibb
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	367
Start date	17 March 2017
Primary completion	20 January 2022
Estimated completion	17 October 2022
Sites	109 locations across France, Hong Kong, Japan, Taiwan, South Korea, Canada, China, Singapore

Drugs / interventions tested

• Nivolumab
• Ipilimumab — full drug profile →
• Pemetrexed — full drug profile →
• Cisplatin (cisplatin) — full drug profile →
• Carboplatin (Carboplatin) — full drug profile →

Conditions studied

• Non-Small-Cell Lung Carcinoma — all drugs for Non-Small-Cell Lung Carcinoma →

Sponsor

Bristol-Myers Squibb — full company profile →

Who can join

18 and older, any sex, with Non-Small-Cell Lung Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival (PFS) by Blinded Independent Centralized Review (BICR) Primary · From randomization to the date of first documented tumor progression or death (approximately 58 months)

PFS is defined as the time between the date of randomization and the date of first documented tumor progression, as determined by BICR (per RECIST v1.1 criteria), or death due to any cause, whichever occurs first. Participants who died without reported progression will be considered to have progressed on the date of their death. Subsequent therapy was accounted for by censoring at the last evaluable tumor assessment on or prior to the date of subsequent therapy. Progression is the appearance of one or more new lesions. RECIST - "response evaluation criteria in solid tumors" is a standard sys

Group	Value	95% CI
Arm A: Nivolumab Plus Platinum-doublet Chemotherapy	5.59	4.47 – 6.80
Arm B: Nivolumab Plus Ipilimumab	1.54	1.41 – 2.63
Arm C: Platinum Doublet Chemotherapy	5.45	4.40 – 5.65

Overall Survival (OS) Secondary · From randomization to the date of death due to any cause (up to approximately 67 months)

Overall Survival (OS) is defined as the time between the date of randomization and the date of death due to any cause. OS will be censored on the last date a participant was known to be alive. Median based on Kaplan-Meier Estimates

Group	Value	95% CI
Arm A: Nivolumab Plus Platinum-doublet Chemotherapy	19.35	16.13 – 20.99
Arm B: Nivolumab Plus Ipilimumab	17.12	13.67 – 23.59
Arm C: Platinum Doublet Chemotherapy	15.90	14.00 – 18.79

Objective Response Rate (ORR) by Blinded Independent Centralized Review (BICR) Secondary · From randomization to the date of objectively documented progression, date of death, or the date of subsequent therapy (up to approximately 67 months)

ORR is number of randomized participants who have confirmed best overall response (BOR) of complete response (CR) or partial response (PR) using RECIST v1.1 criteria by BICR assessment. BOR is the best response designation, between randomization and objectively documented progression per RECIST v1.1 criteria by BICR or the date of subsequent anti-cancer therapy, whichever occurs first. PR is at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as reference. CR is disappearance of all target lesions and a reduction in the short axis of pathologic

Group	Value	95% CI
Arm A: Nivolumab Plus Platinum-doublet Chemotherapy	30.6	23.2 – 38.8
Arm B: Nivolumab Plus Ipilimumab	13.7	6.8 – 23.8
Arm C: Platinum Doublet Chemotherapy	26.7	19.8 – 34.5

Duration of Response (DOR) by Blinded Independent Centralized Review (BICR) Secondary · From randomization to the date of first documented disease progression or death due to any cause (approximately 67 months)

DOR is the time between the date of first response (CR or PR) and the date of first documented disease progression as determined by Response Evaluation Criteria In Solid Tumors (RECIST 1.1) or death due to any cause (death occurring after re-treatment or randomization to new combination treatment was not included), whichever occurred first. PR is at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as reference. CR is disappearance of all target lesions and a reduction in the short axis of pathological lymph nodes to \<10 mm (whether target or no

Group	Value	95% CI
Arm A: Nivolumab Plus Platinum-doublet Chemotherapy	6.67	4.17 – 12.45
Arm B: Nivolumab Plus Ipilimumab	50.04	2.86 – NA
Arm C: Platinum Doublet Chemotherapy	5.55	4.07 – 9.92

9 Month Progression Free Survival Rates (PFSR) by Blinded Independent Centralized Review (BICR) Secondary · 9 months after first treatment dose

The PFSR at 9 months is defined as the percent of treated participants remaining progression free and surviving at 9 months since the first dosing date. Progression is the appearance of one or more new lesions. Point estimates are derived from Kaplan-Meier analyses.

Group	Value	95% CI
Arm A: Nivolumab Plus Platinum-doublet Chemotherapy	25.9	18.4 – 34.0
Arm B: Nivolumab Plus Ipilimumab	12.2	5.5 – 21.7
Arm C: Platinum Doublet Chemotherapy	19.8	12.6 – 28.1

12 Month Progression Free Survival Rates (PFSR) by Blinded Independent Centralized Review (BICR) Secondary · 12 Months after first treatment dose

The PFSR at 12 months is defined as the percent of treated participants remaining progression free and surviving at 12 months since the first dosing date. Progression is the appearance of one or more new lesions. Point estimates are derived from Kaplan-Meier analyses.

Group	Value	95% CI
Arm A: Nivolumab Plus Platinum-doublet Chemotherapy	21.2	14.3 – 29.1
Arm B: Nivolumab Plus Ipilimumab	12.2	5.5 – 21.7
Arm C: Platinum Doublet Chemotherapy	15.9	9.3 – 24.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Participants were assessed for all-cause mortality from their randomization to study completion (up to approximately 67 months.) SAEs and Other AEs was assessed from first dose to 100 days post the last dose of study therapy (up to approximately an average of 11 months and a maximum of 51 months).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A: Nivolumab Plus Platinum-doublet Chemotherapy

Serious: 77/141 (55%)

Deaths: 92/144

Arm B: Nivolumab Plus Ipilimumab

Serious: 46/71 (65%)

Deaths: 55/73

Arm C: Platinum Doublet Chemotherapy

Serious: 55/143 (38%)

Deaths: 105/150

Serious adverse events (132 terms)

Reaction	System	Arm A: Nivolumab Plus Plat…	Arm B: Nivolumab Plus Ipil…	Arm C: Platinum Doublet Ch…
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Pneumonia	Infections and infestations	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Pyrexia	General disorders	—	—	—
Hepatic function abnormal	Hepatobiliary disorders	—	—	—
Cellulitis	Infections and infestations	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—
Deep vein thrombosis	Vascular disorders	—	—	—
Pancytopenia	Blood and lymphatic system disorders	—	—	—
Pericardial effusion	Cardiac disorders	—	—	—
Colitis	Gastrointestinal disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Immune-mediated hepatitis	Hepatobiliary disorders	—	—	—
Influenza	Infections and infestations	—	—	—
Pneumonia aspiration	Infections and infestations	—	—	—
Neutrophil count decreased	Investigations	—	—	—
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Metastases to meninges	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—

Other adverse events (61 terms — click to expand)

Reaction	System	Arm A: Nivolumab Plus Plat…	Arm B: Nivolumab Plus Ipil…	Arm C: Platinum Doublet Ch…
Anaemia	Blood and lymphatic system disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—
Neutrophil count decreased	Investigations	—	—	—
White blood cell count decreased	Investigations	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—
Fatigue	General disorders	—	—	—
Pyrexia	General disorders	—	—	—
Platelet count decreased	Investigations	—	—	—
Oedema peripheral	General disorders	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Insomnia	Psychiatric disorders	—	—	—
Malaise	General disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Blood creatinine increased	Investigations	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—
Hypothyroidism	Endocrine disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Amylase increased	Investigations	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—
Asthenia	General disorders	—	—	—
Hiccups	Respiratory, thoracic and mediastinal disorders	—	—	—
Rash pruritic	Skin and subcutaneous tissue disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—
Productive cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—
Non-cardiac chest pain	General disorders	—	—	—
Conjunctivitis	Infections and infestations	—	—	—
Dysgeusia	Nervous system disorders	—	—	—
Face oedema	General disorders	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—

Most-reported serious reactions: Malignant neoplasm progression, Pneumonia, Dyspnoea, Pneumonitis, Vomiting, Decreased appetite, Anaemia, Nausea.

Data from ClinicalTrials.gov NCT02864251 adverse events section.

Sponsor's own description

The main purpose of this study is to determine whether nivolumab + chemotherapy is effective as compared to chemotherapy in the treatment of patients with EGFR mutation, NSCLC who failed first line (1L) or second-line (2L) EGFR TKI therapy.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Current landscape and future of dual anti-CTLA4 and PD-1/PD-L1 blockade immunotherapy in cancer; lessons learned from clinical trials with melanoma and non-small cell lung cancer (NSCLC).
   Chae YK, Arya A, Iams W, Cruz MR, et al · · 2018 · cited 336× · PMID 29769148 · DOI 10.1186/s40425-018-0349-3
2. Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance.
   Fu K, Xie F, Wang F, Fu L. · · 2022 · cited 271× · PMID 36482474 · DOI 10.1186/s13045-022-01391-4
3. Mechanisms and management of 3rd‑generation EGFR‑TKI resistance in advanced non‑small cell lung cancer (Review).
   He J, Huang Z, Han L, Gong Y, et al · · 2021 · cited 232× · PMID 34558640 · DOI 10.3892/ijo.2021.5270
4. Targeted therapy in advanced non-small cell lung cancer: current advances and future trends.
   Majeed U, Manochakian R, Zhao Y, Lou Y. · · 2021 · cited 193× · PMID 34238332 · DOI 10.1186/s13045-021-01121-2
5. The cutting-edge progress of immune-checkpoint blockade in lung cancer.
   Zhou F, Qiao M, Zhou C. · · 2021 · cited 177× · PMID 33177696 · DOI 10.1038/s41423-020-00577-5
6. Epidermal Growth Factor Receptor (EGFR) Pathway, Yes-Associated Protein (YAP) and the Regulation of Programmed Death-Ligand 1 (PD-L1) in Non-Small Cell Lung Cancer (NSCLC).
   Hsu PC, Jablons DM, Yang CT, You L. · · 2019 · cited 146× · PMID 31387256 · DOI 10.3390/ijms20153821
7. Nivolumab Plus Chemotherapy in Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small-Cell Lung Cancer After Disease Progression on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Final Results of CheckMate 722.
   Mok T, Nakagawa K, Park K, Ohe Y, et al · · 2024 · cited 131× · PMID 38252907 · DOI 10.1200/jco.23.01017
8. Immunotherapy in Treating EGFR-Mutant Lung Cancer: Current Challenges and New Strategies.
   To KKW, Fong W, Cho WCS. · · 2021 · cited 116× · PMID 34113560 · DOI 10.3389/fonc.2021.635007