{"entity":{"id":"paper-overman-checkmate-142-nivolumab-dmmr-colorectal-lancet-oncol-2017","kind":"paper","name":"Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142)","aka":[],"tldr":"Seventy-four heavily pre-treated patients whose bowel cancers had lost DNA mismatch repair were given nivolumab; nearly a third responded and most of those responses were still going a year later.","summary":"In this multicentre, open-label, phase 2 trial, adults with histologically confirmed mismatch repair deficient or microsatellite instability-high metastatic colorectal cancer received nivolumab, with investigator-assessed objective response by RECIST 1.1 as the primary endpoint. Of the 74 patients enrolled between March 2014 and March 2016, 40 (54%) had received three or more previous treatments. At a median follow-up of 12.0 months, 23 patients (31.1%) achieved an objective response and 51 (69%) had disease control for 12 weeks or longer. Median duration of response was not reached, all responders were alive, and 8 had responses lasting 12 months or longer. The most common grade 3 or 4 drug-related adverse events were raised lipase (8%) and amylase (3%), and none of the 23 deaths during the study was considered treatment related.","asOf":"2026-09-24","links":[{"label":"Overman et al., Lancet Oncol 2017: CheckMate 142, nivolumab in 74 patients with dMMR/MSI-high metastatic colorectal cancer","url":"https://doi.org/10.1016/S1470-2045(17)30422-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28734759/"}],"tags":[],"related":["msi-high","dmmr-ihc"],"cancers":["colorectal"],"sections":[],"technologies":["checkpoint-inhibitor","msi-mmr-testing"],"targets":["pd1","mmr"],"drugs":["nivolumab"],"companies":[],"institutions":["md-anderson"],"pathways":["pd1-checkpoint","mismatch-repair-msi"],"terms":["msi","tumour-agnostic"],"trials":["checkmate-8hw"],"people":["scott-kopetz","thierry-andre"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"Lancet Oncology","year":2017,"doi":"10.1016/S1470-2045(17)30422-9","pmid":"28734759","authors":"Overman MJ, McDermott R, Leach JL, et al.","paperType":"rct","findings":["Objective response in 23 of 74 patients (31.1%); disease control for 12 weeks or longer in 69%.","Median duration of response not reached; all responders alive at a median 12 months' follow-up.","Grade 3 or 4 drug-related events uncommon (raised lipase 8%)."],"whatItMeans":"It gave the second PD-1 antibody a colorectal indication in mismatch repair deficient disease and, with the ipilimumab cohort that followed, set up CheckMate 8HW and the first-line combination.","caveats":["Single-arm phase 2 with no control.","Investigator-assessed response.","Mismatch repair status was determined locally by several methods."],"changedPractice":true,"participants":74},"route":"/key-papers/paper-overman-checkmate-142-nivolumab-dmmr-colorectal-lancet-oncol-2017/","neighbours":{"biomarker":[{"id":"dmmr-ihc","kind":"biomarker","name":"dMMR (mismatch repair deficiency by IHC)","route":"/biomarkers/dmmr-ihc/"},{"id":"msi-high","kind":"biomarker","name":"MSI-high (microsatellite instability by PCR or sequencing)","route":"/biomarkers/msi-high/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"msi-mmr-testing","kind":"technology","name":"MSI and mismatch-repair testing","route":"/technologies/msi-mmr-testing/"}],"target":[{"id":"mmr","kind":"target","name":"Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)","route":"/targets/mmr/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}],"institution":[{"id":"md-anderson","kind":"institution","name":"MD Anderson Cancer Center","route":"/institutions/md-anderson/"}],"pathway":[{"id":"mismatch-repair-msi","kind":"pathway","name":"Mismatch repair & microsatellite instability","route":"/pathways/mismatch-repair-msi/"},{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"}],"term":[{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/"}],"trial":[{"id":"checkmate-8hw","kind":"trial","name":"CheckMate 8HW","route":"/trials/checkmate-8hw/"}],"person":[{"id":"scott-kopetz","kind":"person","name":"Scott Kopetz","route":"/people/scott-kopetz/"},{"id":"thierry-andre","kind":"person","name":"Thierry André","route":"/people/thierry-andre/"}],"journal":[{"id":"lancet-oncology","kind":"journal","name":"The Lancet Oncology","route":"/journals/lancet-oncology/"}]}}