{"entity":{"id":"checkmate-8hw","kind":"trial","name":"CheckMate 8HW","aka":[],"tldr":"Showed that a two-drug immunotherapy combination controls mismatch-repair-deficient bowel cancer for over four years on average, and beats immunotherapy alone.","summary":"First-line nivolumab + ipilimumab vs chemotherapy: PFS HR 0.21 (NEJM 2024); at 47 months' follow-up median PFS 54.1 vs 5.9 months. Across all lines, nivolumab + ipilimumab beat nivolumab alone on PFS (Lancet 2025, HR 0.62), the first phase 3 to show the CTLA-4 add-on matters in this setting. FDA approved the combination first line in April 2025. Overall survival is not yet mature.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04008030","url":"https://clinicaltrials.gov/study/NCT04008030"},{"label":"NEJM 2024","url":"https://www.nejm.org/doi/abs/10.1056/NEJMoa2402141"},{"label":"Lancet 2025","url":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02848-4/abstract"}],"tags":[],"related":[],"cancers":["colorectal","msi-high-colorectal"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1","ctla4"],"drugs":["nivolumab","ipilimumab"],"companies":[],"institutions":[],"pathways":[],"terms":["msi"],"trials":["nct05855200"],"people":["thierry-andre","heinz-josef-lenz"],"bottlenecks":[],"keyPapers":["paper-overman-checkmate-142-nivolumab-dmmr-colorectal-lancet-oncol-2017","paper-le-mmr-deficiency-pd1-nejm-2015","paper-andre-checkmate-8hw-nivolumab-ipilimumab-nejm-2024"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04008030","phase":"3","setting":"MSI-H/dMMR metastatic colorectal cancer, all lines: nivolumab + ipilimumab vs nivolumab vs chemotherapy","sponsor":"BMS","result":"First-line PFS 54.1 vs 5.9 months (HR 0.21); combination vs nivolumab PFS HR 0.62.","started":"2019-08-05","startedType":"actual","yearReported":2024,"enrolled":839,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival, first line","primary":true,"unit":"months","arms":[{"name":"Nivolumab + ipilimumab","n":202,"value":54.1},{"name":"Chemotherapy","n":101,"value":5.9}],"hr":0.21,"source":"https://dailynews.ascopubs.org/do/updated-checkmate-8hw-results-nivolumab-ipilimumab-shows-sustained-pfs-benefit-msi-h"},{"endpoint":"Progression-free survival, all lines: combination vs nivolumab","arms":[{"name":"Nivolumab + ipilimumab","n":296},{"name":"Nivolumab","n":286}],"hr":0.62,"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02848-4/abstract"}],"replication":"Consistent with KEYNOTE-177 for PD-1 monotherapy; the doublet-over-monotherapy result is so far unique to this trial."},"route":"/trials/checkmate-8hw/","neighbours":{"cancer":[{"id":"braf-v600e-colorectal","kind":"cancer","name":"BRAF V600E-mutant colorectal cancer","route":"/cancers/braf-v600e-colorectal/"},{"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":"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/"}],"term":[{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"mss-pmmr","kind":"term","name":"Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR)","route":"/terms/mss-pmmr/"}],"trial":[{"id":"checkmate-142","kind":"trial","name":"CheckMate 142","route":"/trials/checkmate-142/"},{"id":"nct05855200","kind":"trial","name":"Study of Perioperative Dostarlimab in Participants With Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon Cancer","route":"/trials/nct05855200/"}],"person":[{"id":"heinz-josef-lenz","kind":"person","name":"Heinz-Josef Lenz","route":"/people/heinz-josef-lenz/"},{"id":"thierry-andre","kind":"person","name":"Thierry André","route":"/people/thierry-andre/"}],"paper":[{"id":"paper-checkmate-8hw-lancet-2025","kind":"paper","name":"CheckMate 8HW: nivolumab plus ipilimumab versus nivolumab alone in MSI-high metastatic colorectal cancer","route":"/key-papers/paper-checkmate-8hw-lancet-2025/"},{"id":"paper-le-mmr-deficiency-pd1-nejm-2015","kind":"paper","name":"Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ","route":"/key-papers/paper-le-mmr-deficiency-pd1-nejm-2015/"},{"id":"paper-le-mmr-deficiency-science-2017","kind":"paper","name":"Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval","route":"/key-papers/paper-le-mmr-deficiency-science-2017/"},{"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)","route":"/key-papers/paper-overman-checkmate-142-nivolumab-dmmr-colorectal-lancet-oncol-2017/"},{"id":"paper-andre-checkmate-8hw-nivolumab-ipilimumab-nejm-2024","kind":"paper","name":"Nivolumab plus ipilimumab in microsatellite-instability-high metastatic colorectal cancer (CheckMate 8HW)","route":"/key-papers/paper-andre-checkmate-8hw-nivolumab-ipilimumab-nejm-2024/"}],"idea":[{"id":"idea-immunotherapy-mss-crc","kind":"idea","name":"Making microsatellite-stable colorectal cancer immunotherapy-responsive","route":"/ideas/idea-immunotherapy-mss-crc/"}],"roadmap":[{"id":"colorectal-roadmap","kind":"roadmap","name":"Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation","route":"/roadmaps/colorectal-roadmap/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"}]}}