{"entity":{"id":"keynote-811","kind":"trial","name":"KEYNOTE-811","aka":[],"tldr":"KEYNOTE-811 showed that adding the immunotherapy pembrolizumab to trastuzumab and chemotherapy shrank HER2-positive stomach cancers more often and kept them under control for longer, with the gain concentrated in tumours that also express PD-L1.","summary":"KEYNOTE-811 randomised 738 patients with previously untreated HER2-positive advanced gastric or gastro-oesophageal junction adenocarcinoma to trastuzumab plus fluoropyrimidine and platinum chemotherapy with pembrolizumab or with placebo. The dual primary endpoints were progression-free and overall survival.\n\nAt the first interim analysis the pembrolizumab arm had a markedly higher objective response rate, which supported accelerated approval in the United States in May 2021. Later analyses showed longer progression-free survival, with the benefit concentrated in tumours with a PD-L1 combined positive score of 1 or more, and the indication was narrowed to that group in 2023. Overall survival results followed in the same direction in the PD-L1-positive population.","status":"positive","asOf":"2026-09-17","links":[{"label":"ClinicalTrials.gov NCT03615326","url":"https://clinicaltrials.gov/study/NCT03615326"}],"tags":["subtype-trials"],"related":[],"cancers":["gastric-her2-positive","gastric"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","trastuzumab","cisplatin","fluorouracil","capecitabine","oxaliplatin"],"companies":["merck"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["yelena-janjigian"],"bottlenecks":[],"keyPapers":["paper-keynote-811-janjigian-lancet-2023"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03615326","phase":"3","setting":"Untreated HER2-positive advanced gastric or gastro-oesophageal junction adenocarcinoma: trastuzumab and fluoropyrimidine-platinum chemotherapy with pembrolizumab or placebo","sponsor":"Merck & Co. (MSD)","result":"Higher response rate and longer progression-free survival with pembrolizumab added to trastuzumab and chemotherapy, with benefit concentrated in PD-L1-positive tumours; accelerated approval in May 2021, later limited to PD-L1 combined positive score of 1 or more.","started":"2018-10-05","startedType":"actual","yearReported":2021,"enrolled":738,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival (second interim analysis)","primary":true,"unit":"months","arms":[{"name":"Pembrolizumab + trastuzumab + chemotherapy","n":350,"value":10,"note":"Median follow-up 28.3 months"},{"name":"Placebo + trastuzumab + chemotherapy","n":348,"value":8.1}],"hr":0.72,"ci":[0.6,0.87],"p":"0.0002","source":"https://doi.org/10.1016/S0140-6736(23)02033-0"},{"endpoint":"Overall survival (second interim analysis)","primary":true,"unit":"months","arms":[{"name":"Pembrolizumab + trastuzumab + chemotherapy","n":350,"value":20},{"name":"Placebo + trastuzumab + chemotherapy","n":348,"value":16.9}],"hr":0.87,"ci":[0.72,1.06],"p":"0.084","source":"https://doi.org/10.1016/S0140-6736(23)02033-0"},{"endpoint":"Progression-free survival (third interim analysis)","unit":"months","arms":[{"name":"Pembrolizumab + trastuzumab + chemotherapy","n":350,"value":10,"note":"Median follow-up 38.4 months"},{"name":"Placebo + trastuzumab + chemotherapy","n":348,"value":8.1}],"hr":0.73,"ci":[0.61,0.87],"source":"https://doi.org/10.1016/S0140-6736(23)02033-0"},{"endpoint":"Overall survival (third interim analysis)","unit":"months","arms":[{"name":"Pembrolizumab + trastuzumab + chemotherapy","n":350,"value":20,"note":"Did not meet prespecified significance criteria; continues to final analysis"},{"name":"Placebo + trastuzumab + chemotherapy","n":348,"value":16.8}],"hr":0.84,"ci":[0.7,1.01],"source":"https://doi.org/10.1016/S0140-6736(23)02033-0"}]},"route":"/trials/keynote-811/","neighbours":{"cancer":[{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"gastric-her2-positive","kind":"cancer","name":"HER2-positive gastric cancer","route":"/cancers/gastric-her2-positive/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"drug":[{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"},{"id":"oxaliplatin","kind":"drug","name":"Oxaliplatin","route":"/drugs/oxaliplatin/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}],"company":[{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"person":[{"id":"yelena-janjigian","kind":"person","name":"Yelena Y. Janjigian","route":"/people/yelena-janjigian/"}],"paper":[{"id":"paper-keynote-811-janjigian-lancet-2023","kind":"paper","name":"KEYNOTE-811: pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma","route":"/key-papers/paper-keynote-811-janjigian-lancet-2023/"}]}}