{"entity":{"id":"keynote-177","kind":"trial","name":"KEYNOTE-177","aka":[],"tldr":"The trial that made immunotherapy alone, with no chemotherapy, the first treatment for the 5% of bowel cancers with a broken DNA spell-checker. Over half of patients were alive at five years.","summary":"Pembrolizumab doubled median PFS (16.5 vs 8.2 months, HR 0.60) and at 5-year follow-up (Annals of Oncology 2024) median OS was 77.5 months with a 5-year OS of 54.8%, despite 62% of chemotherapy patients crossing over to anti-PD-1 therapy. First-line FDA approval June 2020. ESMO-MCBS grade 4. The comparator arm's crossover means the OS hazard ratio (0.73) understates the benefit.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02563002","url":"https://clinicaltrials.gov/study/NCT02563002"},{"label":"5-year follow-up, Annals of Oncology 2024","url":"https://www.annalsofoncology.org/article/S0923-7534(24)04949-4/fulltext"}],"tags":[],"related":[],"cancers":["colorectal","msi-high-colorectal"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["msi"],"trials":["calgb-80405"],"people":["thierry-andre"],"bottlenecks":[],"keyPapers":["paper-le-mmr-deficiency-pd1-nejm-2015","paper-venderbosch-mmr-braf-metastatic-colorectal-pooled-ccr-2014","paper-keynote-177-nejm-2020","paper-keynote-177-lancet-oncol-2022-update"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02563002","phase":"3","setting":"First-line MSI-H/dMMR metastatic colorectal cancer: pembrolizumab vs investigator-choice chemotherapy","sponsor":"Merck","result":"PFS 16.5 vs 8.2 months (HR 0.60); 5-year OS 54.8%, median OS 77.5 months.","started":"2015-11-30","startedType":"actual","yearReported":2020,"enrolled":307,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"Pembrolizumab","n":153,"value":16.5},{"name":"Chemotherapy","n":154,"value":8.2}],"hr":0.6,"ci":[0.45,0.8],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2017699"},{"endpoint":"Overall survival (5-year follow-up)","unit":"months","arms":[{"name":"Pembrolizumab","n":153,"value":77.5},{"name":"Chemotherapy","n":154,"value":36.7}],"hr":0.73,"source":"https://www.annalsofoncology.org/article/S0923-7534(24)04949-4/fulltext"}],"replication":"Consistent with CheckMate 8HW (nivolumab ± ipilimumab) and the earlier single-arm KEYNOTE-164/CheckMate 142 cohorts; the class effect in dMMR CRC is replicated across three antibodies."},"route":"/trials/keynote-177/","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-pdac","kind":"cancer","name":"Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma","route":"/cancers/msi-high-pdac/"},{"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":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"term":[{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"}],"trial":[{"id":"calgb-80405","kind":"trial","name":"CALGB/SWOG 80405","route":"/trials/calgb-80405/"},{"id":"checkmate-142","kind":"trial","name":"CheckMate 142","route":"/trials/checkmate-142/"}],"person":[{"id":"thierry-andre","kind":"person","name":"Thierry André","route":"/people/thierry-andre/"}],"paper":[{"id":"paper-keynote-177-nejm-2020","kind":"paper","name":"KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer","route":"/key-papers/paper-keynote-177-nejm-2020/"},{"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-esmo-metastatic-colorectal-cancer-guideline-ann-oncol-2023","kind":"paper","name":"Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","route":"/key-papers/paper-esmo-metastatic-colorectal-cancer-guideline-ann-oncol-2023/"},{"id":"paper-venderbosch-mmr-braf-metastatic-colorectal-pooled-ccr-2014","kind":"paper","name":"Mismatch repair status and BRAF mutation status in metastatic colorectal cancer: a pooled analysis of the CAIRO, CAIRO2, COIN and FOCUS studies","route":"/key-papers/paper-venderbosch-mmr-braf-metastatic-colorectal-pooled-ccr-2014/"},{"id":"paper-keynote-177-lancet-oncol-2022-update","kind":"paper","name":"Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study","route":"/key-papers/paper-keynote-177-lancet-oncol-2022-update/"}],"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/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}]}}