The central bet in COMPASSION-37 is that blocking two checkpoints at once, PD-1 and CTLA-4 simultaneously, can reach patients that a PD-1 inhibitor alone cannot. Akeso enrolled its first patient this week in the global Phase III trial testing cadonilimab plus chemotherapy against chemotherapy with or without nivolumab as first-line therapy for HER2-negative advanced gastric or gastroesophageal junction cancer, and the PD-L1 question is what makes the design worth watching. Under current NCCN and ESMO guidelines, nivolumab-based regimens are preferentially recommended for patients with PD-L1 combined positive score of 5 or higher, which leaves a sizable fraction of patients with limited immunotherapy options.
The scientific premise comes from COMPASSION-15, the China-based Phase III trial that enrolled 610 patients and reported a median overall survival of 13.9 months with cadonilimab plus chemotherapy versus 11.1 months with placebo plus chemotherapy across the intent-to-treat population. Roughly half that trial’s patients had low PD-L1 expression, and nearly a quarter were PD-L1-negative, proportions higher than in comparable historical studies. The survival benefit held across those subgroups, which is the data point Akeso is now stress-testing globally. For context, the five-year follow-up of CheckMate 649 showed nivolumab plus chemotherapy produced a median OS of 14.4 months in PD-L1 CPS-positive patients, with the benefit concentrated in that high-expressing group.
COMPASSION-37 is designed to answer whether that Chinese Phase III signal holds across geographically and ethnically diverse populations and whether it can beat nivolumab head-to-head rather than placebo. The trial, formally AK104-311, is co-led by investigators including Yelena Janjigian of Memorial Sloan Kettering, Markus Möhler of Johannes Gutenberg University Mainz, and Lin Shen and Jiafu Ji of Peking University Cancer Hospital. Janjigian and Möhler both served as investigators on CheckMate 649, the trial that set nivolumab as the current global benchmark, so the principal investigator roster is not incidental to the trial’s credibility with regulators and oncology guideline committees.
Cadonilimab holds EMA orphan designation for gastric cancer in the European Union but has not received marketing approval there. COMPASSION-37’s enrollment of Western patients is the step that could change that calculus. The number to track as the trial runs is overall survival in the PD-L1-low subgroup: if the dual-blockade signal from COMPASSION-15 replicates in a Western population against an active comparator, it redraws which patients are considered candidates for front-line immunotherapy.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
