Full Breakdown
Global Phase III COMPASSION-37 Trial Enrolls First Patient
By Drooid · · How we work
Core Event: First Patient Enrolled in COMPASSION-37
Akeso, Inc. reported that the first participant has been enrolled in COMPASSION-37 (AK104-311), a worldwide, multicenter Phase III study comparing cadonilimab + chemotherapy with chemotherapy ± nivolumab as first-line therapy for HER2-negative, unresectable or metastatic gastric or gastro-esophageal junction (G/GEJ) adenocarcinoma. The trial is designed as a head-to-head evaluation of the PD-1/CTLA-4 bispecific antibody cadonilimab against the current international standard of care.
Background & Context
PD-1 inhibitor + chemotherapy regimens, such as nivolumab + chemotherapy, have become the accepted first-line approach for HER2-negative advanced gastric cancer, especially for patients with PD-L1 combined positive score (CPS) >= 5 per NCCN and ESMO guidelines. However, patients with low PD-L1 expression lack effective immunotherapy options, creating a global unmet need. Earlier Chinese Phase III data (COMPASSION-15) showed a survival benefit for cadonilimab + chemotherapy across PD-L1 subgroups, prompting a broader international evaluation.
Key Figures & Groups
- Yelena Y. Janjigian, MD, FASCO – Chief of the Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center; global principal investigator for COMPASSION-37.
- Markus Möhler, PhD – Professor, Johannes Gutenberg University Mainz, Germany; co-principal investigator.
- Jiafu Ji, MD – Director, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute; co-principal investigator.
- Lin Shen, MD – Director, Department of Gastrointestinal Oncology, Peking University Cancer Hospital; co-principal investigator.
Timeline
- Prior to enrollment: Completion of COMPASSION-15 (610 patients, Chinese Phase III) demonstrating cadonilimab’s efficacy regardless of PD-L1 status.
- Current: First patient enrollment in COMPASSION-37, marking the start of global recruitment across diverse geographic and ethnic populations.
- Future: Ongoing enrollment worldwide; a parallel Phase II peri-operative study (NCT07631000) led by Dr. Janjigian in the United States is also enrolling.
Data & Statistics
- COMPASSION-15 enrolled 610 patients, with 49.8 % exhibiting low PD-L1 expression and 23 % PD-L1-negative disease.
- In COMPASSION-15, cadonilimab + chemotherapy significantly reduced the risk of death versus control, independent of PD-L1 status.
Why It Matters
If COMPASSION-37 confirms the earlier Chinese findings, cadonilimab could become the first approved bispecific antibody to broaden first-line immunotherapy benefits to patients with low or negative PD-L1 expression. This would address a major therapeutic gap and potentially shift treatment standards from PD-L1-selected regimens to a more inclusive approach.
Official Statements & Responses
Dr. Janjigian emphasized that immunotherapy has already extended survival for stomach and esophageal cancers and that the trial aims to determine whether cadonilimab can further improve outcomes, especially for patients with low PD-L1 expression. Professor Ji highlighted the trial’s role in generating rigorous global evidence to assess the regimen’s value across regions and PD-L1 subgroups. Professor Shen noted the study’s purpose of clarifying the benefit of dual PD-1/CTLA-4 blockade across diverse patient populations.
What’s Next
The trial will continue enrolling patients worldwide, with efficacy and safety data to be analyzed after sufficient follow-up. Results are expected to inform whether cadonilimab can be adopted as a new first-line option for HER2-negative advanced gastric cancer, particularly for those who currently lack effective immunotherapy alternatives.
