IND.227 / KEYNOTE-483

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.