{"entity":{"id":"checkmate-026","kind":"trial","name":"CheckMate 026","aka":[],"tldr":"The trial that showed a PD-1 antibody can fail in the first line if the PD-L1 threshold is set too low, and the reason the 50 percent cut-off exists.","summary":"KEYNOTE-024 and CheckMate 026 asked the same question at nearly the same time and got opposite answers. KEYNOTE-024 used pembrolizumab with a PD-L1 tumour proportion score threshold of 50 percent; CheckMate 026 used nivolumab with a threshold of 1 percent for entry and 5 percent for the primary analysis.\n\nAmong the 423 patients with PD-L1 expression of 5 percent or more, median progression-free survival was 4.2 months with nivolumab against 5.9 months with chemotherapy (hazard ratio 1.15, 95 percent confidence interval 0.91 to 1.45, p=0.25), and median overall survival was 14.4 against 13.2 months (hazard ratio 1.02, 0.80 to 1.30). Sixty percent of the chemotherapy arm crossed over to nivolumab. Treatment-related adverse events of any grade occurred in 71 percent on nivolumab and 92 percent on chemotherapy, and grade 3 or 4 events in 18 against 51 percent.\n\nThe failure is usually explained by the threshold and by an imbalance that put more patients with poor prognostic features in the nivolumab arm. Whatever the cause, CheckMate 026 is why single-agent PD-1 blockade in the first line is restricted to high PD-L1 expression, and why nivolumab's first-line indication came only later, with ipilimumab in CheckMate 227 and with chemotherapy in CheckMate 9LA.","status":"negative","asOf":"2026-09-25","links":[{"label":"ClinicalTrials.gov NCT02041533","url":"https://clinicaltrials.gov/study/NCT02041533"},{"label":"CheckMate 026 (New England Journal of Medicine 2017)","url":"https://doi.org/10.1056/NEJMoa1613493"}],"tags":[],"related":[],"cancers":["nsclc","pdl1-high-nsclc"],"sections":[],"technologies":["checkpoint-inhibitor","companion-diagnostic","platinum"],"targets":["pd1","pdl1"],"drugs":["nivolumab","carboplatin","cisplatin"],"companies":["bms"],"institutions":[],"pathways":[],"terms":["tps","pd-l1-testing"],"trials":["keynote-024-189","checkmate-227","checkmate-9la"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02041533","phase":"3","setting":"Untreated stage IV or recurrent non-small-cell lung cancer with PD-L1 on 1 percent or more of tumour cells: nivolumab 3 mg/kg every two weeks versus platinum-based chemotherapy, with progression-free survival in the PD-L1 5 percent or more population as the primary endpoint and crossover permitted","sponsor":"Bristol-Myers Squibb","result":"Median progression-free survival 4.2 against 5.9 months (hazard ratio 1.15, p=0.25) and overall survival 14.4 against 13.2 months (hazard ratio 1.02): the primary endpoint was not met.","yearReported":2017,"enrolled":541,"enrolledBasis":"randomised","enrolledNote":"423 patients with PD-L1 expression of 5 percent or more formed the primary analysis population; the registry figure counts all randomised patients.","outcomes":[{"endpoint":"Progression-free survival (PD-L1 5 percent or more)","primary":true,"unit":"months","arms":[{"name":"Nivolumab","value":4.2},{"name":"Platinum-based chemotherapy","value":5.9}],"hr":1.15,"ci":[0.91,1.45],"p":"0.25","source":"https://doi.org/10.1056/NEJMoa1613493"},{"endpoint":"Overall survival (PD-L1 5 percent or more)","unit":"months","arms":[{"name":"Nivolumab","value":14.4},{"name":"Platinum-based chemotherapy","value":13.2}],"hr":1.02,"ci":[0.8,1.3],"source":"https://doi.org/10.1056/NEJMoa1613493"}]},"route":"/trials/checkmate-026/","neighbours":{"cancer":[{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pdl1-high-nsclc","kind":"cancer","name":"PD-L1-high non-small-cell lung cancer without a driver mutation","route":"/cancers/pdl1-high-nsclc/"}],"technology":[{"id":"companion-diagnostic","kind":"technology","name":"Companion diagnostics","route":"/technologies/companion-diagnostic/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}],"company":[{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"}],"term":[{"id":"lung-failed-programmes","kind":"term","name":"Lung cancer: the failed and stopped programmes, and why","route":"/terms/lung-failed-programmes/"},{"id":"pd-l1-testing","kind":"term","name":"PD-L1 expression testing (22C3, SP142, SP263)","route":"/terms/pd-l1-testing/"},{"id":"tps","kind":"term","name":"Tumour proportion score (TPS)","route":"/terms/tps/"}],"trial":[{"id":"checkmate-227","kind":"trial","name":"CheckMate 227","route":"/trials/checkmate-227/"},{"id":"checkmate-9la","kind":"trial","name":"CheckMate 9LA","route":"/trials/checkmate-9la/"},{"id":"keynote-024-189","kind":"trial","name":"KEYNOTE-024 & KEYNOTE-189","route":"/trials/keynote-024-189/"}]}}