{"entity":{"id":"checkmate-142","kind":"trial","name":"CheckMate 142","aka":[],"tldr":"The trial that first showed checkpoint immunotherapy works in mismatch-repair deficient bowel cancer, and that adding a second antibody makes it work better.","summary":"CheckMate 142 is the multi-cohort phase 2 that established immunotherapy in mismatch-repair deficient metastatic colorectal cancer. In the nivolumab-with-ipilimumab dMMR cohort of 119 patients, 76 percent of whom had received two or more previous systemic therapies, the investigator-assessed objective response rate was 55 percent (95% CI 45.2 to 63.8) and disease control for at least twelve weeks 80 percent; median duration of response was not reached and 94 percent of responses were continuing at data cutoff. Progression-free survival was 76 percent at nine months and 71 percent at twelve, and overall survival 87 and 85 percent. Grade 3 to 4 treatment-related events affected 32 percent. The microsatellite-stable cohorts were the mirror image: a later report of nivolumab, ipilimumab and cobimetinib in 30 patients with MSS or proficient mismatch repair disease found an objective response rate of 3 percent and median overall survival 8.2 months, and concluded that the regimen should not be pursued. CheckMate 142 led to the 2017 and 2018 accelerated approvals and set up KEYNOTE-177 and CheckMate 8HW.","status":"positive","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov NCT02060188","url":"https://clinicaltrials.gov/study/NCT02060188"},{"label":"CheckMate 142: durable clinical benefit with nivolumab plus ipilimumab in dMMR metastatic colorectal cancer (Journal of Clinical Oncology 2018)","url":"https://doi.org/10.1200/JCO.2017.76.9901"},{"label":"CheckMate 142: nivolumab, ipilimumab and cobimetinib in MSS metastatic colorectal cancer (ESMO Gastrointestinal Oncology 2026)","url":"https://doi.org/10.1016/j.esmogo.2026.100334"}],"tags":[],"related":[],"cancers":["colorectal","msi-high-colorectal"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1","ctla4","mek"],"drugs":["nivolumab","ipilimumab","cobimetinib"],"companies":["bms"],"institutions":[],"pathways":[],"terms":["msi","cold-vs-hot"],"trials":["keynote-177","checkmate-8hw","imblaze370"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02060188","phase":"2","setting":"Recurrent or metastatic colorectal cancer, MSI-high and non-MSI-high cohorts: nivolumab alone or with ipilimumab, and later cohorts adding cobimetinib, daratumumab or relatlimab","sponsor":"Bristol Myers Squibb","result":"dMMR nivolumab plus ipilimumab cohort: objective response 55 percent, twelve-month overall survival 85 percent. MSS cohort with cobimetinib: objective response 3 percent.","yearReported":2018,"enrolled":385,"enrolledBasis":"registry","outcomes":[{"endpoint":"Objective response rate (dMMR, nivolumab plus ipilimumab)","primary":true,"unit":"percent","arms":[{"name":"Nivolumab plus ipilimumab","n":119,"value":55}],"ci":[45.2,63.8],"source":"https://doi.org/10.1200/JCO.2017.76.9901"},{"endpoint":"Objective response rate (MSS, nivolumab, ipilimumab and cobimetinib)","unit":"percent","arms":[{"name":"Nivolumab, ipilimumab and cobimetinib","n":30,"value":3}],"source":"https://doi.org/10.1016/j.esmogo.2026.100334"}],"replication":"KEYNOTE-177 and CheckMate 8HW confirmed the dMMR effect in randomised phase 3 trials; the MSS cohorts agree with IMblaze370."},"route":"/trials/checkmate-142/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"msi-high-colorectal","kind":"cancer","name":"Mismatch-repair deficient (MSI-high) colorectal cancer","route":"/cancers/msi-high-colorectal/"}],"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":"mek","kind":"target","name":"MEK1/2","route":"/targets/mek/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"cobimetinib","kind":"drug","name":"Cobimetinib","route":"/drugs/cobimetinib/"},{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}],"company":[{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"}],"term":[{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"}],"trial":[{"id":"checkmate-8hw","kind":"trial","name":"CheckMate 8HW","route":"/trials/checkmate-8hw/"},{"id":"imblaze370","kind":"trial","name":"IMblaze370","route":"/trials/imblaze370/"},{"id":"keynote-177","kind":"trial","name":"KEYNOTE-177","route":"/trials/keynote-177/"}]}}