{"entity":{"id":"checkmate-9la","kind":"trial","name":"CheckMate 9LA","aka":[],"tldr":"Used just two cycles of chemotherapy to cover the first weeks while dual immunotherapy takes effect, an answer to the criticism that immunotherapy alone is too slow for people with heavy disease.","summary":"CheckMate 227 had shown that nivolumab with ipilimumab beats chemotherapy in the first line, but the survival curves cross early: patients with a large tumour burden can progress before dual checkpoint blockade works. CheckMate 9LA tested a limited course of chemotherapy as a bridge. It randomised 719 of 1,150 enrolled patients at 103 hospitals in 19 countries between August 2017 and January 2019 to nivolumab 360 mg every three weeks with ipilimumab 1 mg/kg every six weeks plus two cycles of platinum doublet chemotherapy (361), or to four cycles of chemotherapy alone (358), stratified by histology, sex and PD-L1 expression.\n\nAt the preplanned interim analysis with a median 9.7 months of follow-up, median overall survival was 14.1 months (95 percent confidence interval 13.2 to 16.2) against 10.7 months (9.5 to 12.4), hazard ratio 0.69 (96.71 percent confidence interval 0.55 to 0.87, p=0.00065). With 3.5 months more follow-up it was 15.6 months (13.9 to 20.0) against 10.9.\n\nThe FDA approved the regimen in 2020. England is the exception: NICE TA724 (8 September 2021) does not recommend nivolumab with ipilimumab and two cycles of platinum doublet chemotherapy for untreated metastatic disease, so the regimen is not routinely funded there even though it is a standard option in the United States and much of Europe.","status":"positive","asOf":"2026-09-25","links":[{"label":"ClinicalTrials.gov NCT03215706","url":"https://clinicaltrials.gov/study/NCT03215706"},{"label":"CheckMate 9LA (Lancet Oncology 2021)","url":"https://doi.org/10.1016/S1470-2045(20)30641-0"},{"label":"NICE TA724: nivolumab with ipilimumab and chemotherapy for untreated metastatic non-small-cell lung cancer (not recommended)","url":"https://www.nice.org.uk/guidance/ta724"}],"tags":[],"related":[],"cancers":["nsclc","lung-squamous-cell-carcinoma","lung-adenocarcinoma"],"sections":[],"technologies":["checkpoint-inhibitor","cytotoxic-chemotherapy","platinum"],"targets":["pd1","ctla4"],"drugs":["nivolumab","ipilimumab","carboplatin","cisplatin","pemetrexed","paclitaxel"],"companies":["bms"],"institutions":[],"pathways":[],"terms":["immune-checkpoint","tps"],"trials":["checkmate-227","nct03164616"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03215706","phase":"3","setting":"Treatment-naive stage IV or recurrent non-small-cell lung cancer of any PD-L1 level: nivolumab 360 mg every three weeks with ipilimumab 1 mg/kg every six weeks plus two cycles of histology-based platinum doublet chemotherapy, versus four cycles of chemotherapy alone, with overall survival as the primary endpoint","sponsor":"Bristol-Myers Squibb","result":"Median overall survival 14.1 against 10.7 months at the interim analysis (hazard ratio 0.69, p=0.00065), and 15.6 against 10.9 months with longer follow-up.","yearReported":2020,"enrolled":719,"enrolledBasis":"randomised","enrolledNote":"1,150 patients were enrolled and 719 randomised; the registry figure counts enrolment.","outcomes":[{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"Nivolumab, ipilimumab and two cycles of chemotherapy","n":361,"value":14.1},{"name":"Four cycles of chemotherapy","n":358,"value":10.7}],"hr":0.69,"ci":[0.55,0.87],"p":"0.00065","source":"https://doi.org/10.1016/S1470-2045(20)30641-0"}],"replication":"POSEIDON reproduced the idea with durvalumab, tremelimumab and chemotherapy (median overall survival 14.0 against 11.7 months, hazard ratio 0.77)."},"route":"/trials/checkmate-9la/","neighbours":{"cancer":[{"id":"lung-adenocarcinoma","kind":"cancer","name":"Adenocarcinoma of the lung","route":"/cancers/lung-adenocarcinoma/"},{"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":"lung-squamous-cell-carcinoma","kind":"cancer","name":"Squamous cell carcinoma of the lung","route":"/cancers/lung-squamous-cell-carcinoma/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"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":"ctla4","kind":"target","name":"CTLA-4","route":"/targets/ctla4/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"pemetrexed","kind":"drug","name":"Pemetrexed","route":"/drugs/pemetrexed/"}],"company":[{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"}],"term":[{"id":"immune-checkpoint","kind":"term","name":"Immune checkpoint","route":"/terms/immune-checkpoint/"},{"id":"tps","kind":"term","name":"Tumour proportion score (TPS)","route":"/terms/tps/"}],"trial":[{"id":"checkmate-026","kind":"trial","name":"CheckMate 026","route":"/trials/checkmate-026/"},{"id":"checkmate-227","kind":"trial","name":"CheckMate 227","route":"/trials/checkmate-227/"},{"id":"nct03164616","kind":"trial","name":"Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON).","route":"/trials/nct03164616/"}]}}