{"entity":{"id":"keynote-483","kind":"trial","name":"IND.227 / KEYNOTE-483","aka":[],"tldr":"Showed that adding a PD-1 blocker to standard chemotherapy helps in mesothelioma, giving a second immunotherapy-based first-line option.","summary":"IND.227, also KEYNOTE-483, trial NCT02784171 sponsored by the Canadian Cancer Trials Group with Merck and reported in 2023, showed that adding pembrolizumab to platinum and pemetrexed helps in unresectable pleural mesothelioma, giving a second immunotherapy-based first-line option. It randomised 440 patients, met its primary overall survival endpoint with a modest effect and a much higher response rate, with benefit again concentrated in non-epithelioid disease, and led to FDA approval on 17 September 2024; it was an academic-led trial with industry drug supply. OnCo links it to mesothelioma, pembrolizumab, pemetrexed, the epithelioid versus sarcomatoid term and the histology pairing; DREAM supported it in phase 2, but the DREAM3R phase 3 was stopped early and BEAT-meso missed survival. Whether the modest benefit holds up outside non-epithelioid disease is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02784171","url":"https://clinicaltrials.gov/study/NCT02784171"},{"label":"Merck OS announcement","url":"https://www.merck.com/news/keytruda-pembrolizumab-plus-chemotherapy-significantly-improved-overall-survival-versus-chemotherapy-alone-as-first-line-treatment-for-advanced-malignant-pleural-mesothelioma/"}],"tags":[],"related":[],"cancers":["mesothelioma","pleural-mesothelioma"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","pemetrexed"],"companies":["cctg"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02784171","phase":"2/3","setting":"Unresectable pleural mesothelioma, first line: pembrolizumab + platinum-pemetrexed vs platinum-pemetrexed","sponsor":"Canadian Cancer Trials Group / Merck","result":"OS 17.3 vs 16.1 months, HR 0.79; ORR 52% vs 29%.","started":"2016-11-11","startedType":"actual","yearReported":2023,"enrolled":440,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"Pembrolizumab + chemotherapy","n":222,"value":17.3},{"name":"Chemotherapy","n":218,"value":16.1}],"hr":0.79,"ci":[0.64,0.98],"p":"0.0324","source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01613-6/fulltext"},{"endpoint":"Objective response rate","unit":"%","arms":[{"name":"Pembrolizumab + chemotherapy","value":52},{"name":"Chemotherapy","value":29}],"source":"https://doi.org/10.1016/S0140-6736(23)01883-4"}],"replication":"Supported by DREAM (phase 2, durvalumab + chemotherapy) but DREAM3R phase 3 was stopped early; BEAT-meso (atezolizumab + bevacizumab + chemotherapy) missed OS."},"route":"/trials/keynote-483/","neighbours":{"cancer":[{"id":"mesothelioma","kind":"cancer","name":"Mesothelioma","route":"/cancers/mesothelioma/"},{"id":"pleural-mesothelioma","kind":"cancer","name":"Pleural mesothelioma","route":"/cancers/pleural-mesothelioma/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"pemetrexed","kind":"drug","name":"Pemetrexed","route":"/drugs/pemetrexed/"}],"company":[{"id":"cctg","kind":"company","name":"Canadian Cancer Trials Group (CCTG)","route":"/companies/cctg/"}],"term":[{"id":"epithelioid-vs-sarcomatoid","kind":"term","name":"Epithelioid vs sarcomatoid (biphasic) mesothelioma","route":"/terms/epithelioid-vs-sarcomatoid/"}],"pairing":[{"id":"histology-directs-first-line-meso","kind":"pairing","name":"Histology → first-line choice in mesothelioma","route":"/pairings/histology-directs-first-line-meso/"}],"paper":[{"id":"paper-keynote-483-lancet-2023","kind":"paper","name":"KEYNOTE-483 (CCTG IND.227): pembrolizumab plus chemotherapy versus chemotherapy in untreated pleural mesothelioma","route":"/key-papers/paper-keynote-483-lancet-2023/"}]}}