{"entity":{"id":"keynote-859","kind":"trial","name":"KEYNOTE-859","aka":[],"tldr":"Confirmed that adding a PD-1 blocker to first-line chemotherapy helps in stomach cancer, with the biggest gain in tumours rich in PD-L1.","summary":"KEYNOTE-859, trial NCT03675737 sponsored by Merck and reported in 2023, confirmed that adding the PD-1 antibody pembrolizumab to first-line chemotherapy helps in HER2-negative advanced gastric and gastro-oesophageal junction adenocarcinoma, with the biggest gain in tumours rich in PD-L1. It randomised 1,579 patients and met its primary overall survival endpoint in all randomised patients, with progressively larger effects at CPS 1 and CPS 10 or higher, leading to FDA approval in November 2023 for all PD-L1 levels while the EMA restricted it to CPS 1 or higher. OnCo links it to gastric cancer, PD-1 as a target, pembrolizumab, the CPS term and Sun Young Rha, and it replicates CheckMate 649. As with its predecessor, whether PD-L1-negative patients should receive immunotherapy is the open question the regional labels disagree on.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03675737","url":"https://clinicaltrials.gov/study/NCT03675737"}],"tags":[],"related":[],"cancers":["gastric","gastric-pdl1-high"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["cps"],"trials":[],"people":["rha-sun-young"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03675737","phase":"3","setting":"First-line HER2-negative advanced gastric/GEJ adenocarcinoma: pembrolizumab + chemotherapy vs placebo + chemotherapy","sponsor":"Merck","result":"OS HR 0.78 (all); CPS ≥10 OS 15.7 vs 11.8 months (HR 0.65).","started":"2018-11-08","startedType":"actual","yearReported":2023,"enrolled":1579,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival, all randomised","primary":true,"unit":"months","arms":[{"name":"Pembrolizumab + chemotherapy","n":790,"value":12.9},{"name":"Placebo + chemotherapy","n":789,"value":11.5}],"hr":0.78,"ci":[0.7,0.87],"source":"https://www.annalsofoncology.org/article/S0923-7534(24)04258-3/fulltext"},{"endpoint":"Overall survival, CPS ≥10","unit":"months","arms":[{"name":"Pembrolizumab + chemotherapy","value":15.7},{"name":"Placebo + chemotherapy","value":11.8}],"hr":0.65,"ci":[0.53,0.79],"source":"https://www.annalsofoncology.org/article/S0923-7534(24)04258-3/fulltext"}],"replication":"Replicates CheckMate 649."},"route":"/trials/keynote-859/","neighbours":{"cancer":[{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"gastric-msi-high","kind":"cancer","name":"Microsatellite-unstable (MSI-high) gastric cancer","route":"/cancers/gastric-msi-high/"},{"id":"gastric-pdl1-high","kind":"cancer","name":"PD-L1-high gastric cancer","route":"/cancers/gastric-pdl1-high/"}],"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":"cps","kind":"term","name":"Combined positive score (CPS)","route":"/terms/cps/"}],"person":[{"id":"rha-sun-young","kind":"person","name":"Sun Young Rha","route":"/people/rha-sun-young/"}],"paper":[{"id":"paper-keynote-859-lancet-oncol-2023","kind":"paper","name":"KEYNOTE-859: pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer","route":"/key-papers/paper-keynote-859-lancet-oncol-2023/"}]}}