{"entity":{"id":"checkmate-648","kind":"trial","name":"CheckMate 648","aka":[],"tldr":"Showed two immunotherapy options for squamous oesophageal cancer, including one with no chemotherapy at all, both extending survival.","summary":"CheckMate 648, trial NCT03143153 sponsored by Bristol Myers Squibb and reported in 2021, showed two immunotherapy options for first-line advanced oesophageal squamous cell carcinoma, nivolumab plus chemotherapy and a chemotherapy-free doublet of nivolumab plus ipilimumab, both extending survival. It randomised 970 patients across three arms and met its primary overall survival endpoint in PD-L1-positive patients for both regimens, with benefit in all randomised patients and durable separation confirmed at five-year follow-up in 2026, leading to FDA approval of both regimens in May 2022. OnCo links it to oesophageal cancer, PD-1 and CTLA-4 as targets, nivolumab, ipilimumab and Jaffer A. Ajani. Which patients are best served by avoiding chemotherapy altogether is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03143153","url":"https://clinicaltrials.gov/study/NCT03143153"},{"label":"5-year follow-up","url":"https://pubmed.ncbi.nlm.nih.gov/42575473/"}],"tags":[],"related":[],"cancers":["esophageal","oesophageal-squamous-cell-carcinoma"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1","ctla4"],"drugs":["nivolumab","ipilimumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["jaffer-ajani"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03143153","phase":"3","setting":"First-line advanced oesophageal squamous cell carcinoma: nivolumab + chemotherapy, or nivolumab + ipilimumab (chemotherapy-free), vs chemotherapy","sponsor":"BMS","result":"PD-L1 ≥1%: OS 15.4 vs 9.1 months (nivo + chemo, HR 0.54); 13.7 vs 9.1 months (nivo + ipi, HR 0.64).","started":"2017-06-29","startedType":"actual","yearReported":2021,"enrolled":970,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival, PD-L1 ≥1% (nivolumab + chemotherapy)","primary":true,"unit":"months","arms":[{"name":"Nivolumab + chemotherapy","value":15.4},{"name":"Chemotherapy","value":9.1}],"hr":0.54,"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2111380"},{"endpoint":"Overall survival, PD-L1 ≥1% (nivolumab + ipilimumab)","unit":"months","arms":[{"name":"Nivolumab + ipilimumab","value":13.7},{"name":"Chemotherapy","value":9.1}],"hr":0.64,"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2111380"}],"replication":"Consistent with KEYNOTE-590 and RATIONALE-306; the chemotherapy-free doublet is unique to this trial."},"route":"/trials/checkmate-648/","neighbours":{"cancer":[{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"oesophageal-squamous-cell-carcinoma","kind":"cancer","name":"Oesophageal squamous cell carcinoma","route":"/cancers/oesophageal-squamous-cell-carcinoma/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"ctla4","kind":"target","name":"CTLA-4","route":"/targets/ctla4/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}],"person":[{"id":"jaffer-ajani","kind":"person","name":"Jaffer A. Ajani","route":"/people/jaffer-ajani/"}],"paper":[{"id":"paper-checkmate-648-nejm-2022","kind":"paper","name":"CheckMate 648: nivolumab combination therapy in advanced oesophageal squamous cell carcinoma","route":"/key-papers/paper-checkmate-648-nejm-2022/"}]}}