CheckMate 649

CheckMate 649, trial NCT02872116 sponsored by Bristol Myers Squibb and reported in 2020, is the largest phase 3 in gastric cancer and the trial that added immunotherapy to first-line chemotherapy, with a durable minority of long-term survivors among patients with PD-L1-rich tumours at five years. It randomised 1,581 patients with HER2-negative gastric, gastro-oesophageal junction or oesophageal adenocarcinoma to nivolumab plus chemotherapy or chemotherapy and met its primary overall survival endpoint in the PD-L1 CPS 5 or higher population, with a smaller benefit in all randomised patients; the FDA approved it for all patients in 2021 while the EMA and many guidelines restrict it to CPS 5 or higher. Whether PD-L1-low patients gain anything is the open question.