{"entity":{"id":"checkmate-649","kind":"trial","name":"CheckMate 649","aka":[],"tldr":"The trial that added immunotherapy to first-line stomach cancer chemotherapy; at five years, 16% of patients with PD-L1-rich tumours were alive versus 6%.","summary":"CheckMate 649, trial NCT02872116 sponsored by Bristol Myers Squibb and reported in 2020, is the largest phase 3 in gastric cancer and the trial that added immunotherapy to first-line chemotherapy, with a durable minority of long-term survivors among patients with PD-L1-rich tumours at five years. It randomised 1,581 patients with HER2-negative gastric, gastro-oesophageal junction or oesophageal adenocarcinoma to nivolumab plus chemotherapy or chemotherapy and met its primary overall survival endpoint in the PD-L1 CPS 5 or higher population, with a smaller benefit in all randomised patients; the FDA approved it for all patients in 2021 while the EMA and many guidelines restrict it to CPS 5 or higher. Whether PD-L1-low patients gain anything is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02872116","url":"https://clinicaltrials.gov/study/NCT02872116"},{"label":"5-year follow-up, Annals of Oncology 2026","url":"https://www.annalsofoncology.org/article/S0923-7534(26)00059-1/fulltext"}],"tags":[],"related":[],"cancers":["gastric","gastric-pdl1-high","gastric-msi-high","esophageal"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1","pdl1"],"drugs":["nivolumab","capox","folfox"],"companies":[],"institutions":[],"pathways":[],"terms":["cps"],"trials":[],"people":["kang-won-ki","jaffer-ajani","yelena-janjigian"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02872116","phase":"3","setting":"First-line HER2-negative advanced gastric/GEJ/oesophageal adenocarcinoma: nivolumab + chemotherapy vs chemotherapy","sponsor":"BMS","result":"CPS ≥5: OS 14.4 vs 11.1 months (HR 0.71); 5-year OS 16% vs 6%.","started":"2016-10-12","startedType":"actual","yearReported":2020,"enrolled":1581,"enrolledBasis":"randomised","enrolledNote":"ClinicalTrials.gov lists 2,031 participants (actual) across all three arms; the Lancet 2021 primary analysis concurrently randomised 1,581 patients to nivolumab plus chemotherapy or chemotherapy alone, leaving out the nivolumab plus ipilimumab arm.","outcomes":[{"endpoint":"Overall survival, PD-L1 CPS ≥5","primary":true,"unit":"months","arms":[{"name":"Nivolumab + chemotherapy","n":473,"value":14.4},{"name":"Chemotherapy","n":482,"value":11.1}],"hr":0.71,"ci":[0.61,0.81],"source":"https://www.annalsofoncology.org/article/S0923-7534(26)00059-1/fulltext"},{"endpoint":"Overall survival at 5 years, CPS ≥5","unit":"percent","arms":[{"name":"Nivolumab + chemotherapy","value":16},{"name":"Chemotherapy","value":6}],"source":"https://www.annalsofoncology.org/article/S0923-7534(26)00059-1/fulltext"}],"replication":"Replicated by KEYNOTE-859 (pembrolizumab), RATIONALE-305 (tislelizumab), and ORIENT-16 (sintilimab)."},"route":"/trials/checkmate-649/","neighbours":{"cancer":[{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"gastric-msi-high","kind":"cancer","name":"Microsatellite-unstable (MSI-high) gastric cancer","route":"/cancers/gastric-msi-high/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"gastric-pdl1-high","kind":"cancer","name":"PD-L1-high gastric cancer","route":"/cancers/gastric-pdl1-high/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"drug":[{"id":"capox","kind":"drug","name":"CAPOX (capecitabine, oxaliplatin)","route":"/drugs/capox/"},{"id":"folfox","kind":"drug","name":"FOLFOX (5-FU, leucovorin, oxaliplatin)","route":"/drugs/folfox/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}],"term":[{"id":"cps","kind":"term","name":"Combined positive score (CPS)","route":"/terms/cps/"}],"person":[{"id":"jaffer-ajani","kind":"person","name":"Jaffer A. Ajani","route":"/people/jaffer-ajani/"},{"id":"kang-won-ki","kind":"person","name":"Won Ki Kang","route":"/people/kang-won-ki/"},{"id":"yelena-janjigian","kind":"person","name":"Yelena Y. Janjigian","route":"/people/yelena-janjigian/"}],"idea":[{"id":"idea-biomarker-quadruplet-gastric","kind":"idea","name":"Biomarker-directed first-line quadruplets in gastric cancer","route":"/ideas/idea-biomarker-quadruplet-gastric/"}],"roadmap":[{"id":"chemotherapy-roadmap","kind":"roadmap","name":"Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs","route":"/roadmaps/chemotherapy-roadmap/"}]}}