One antibody, two immune brakes. That is the idea behind cadonilimab, and Akeso has now put it into a head-to-head test against the current standard in stomach cancer. On September 27 the Hong Kong-listed company said the first patient had been enrolled in COMPASSION-37, a global Phase III trial run across multiple centers.
Cadonilimab is a bispecific antibody that targets PD-1 and CTLA-4, two checkpoints the immune system uses as off switches. The trial asks whether blocking both at once beats the usual approach. Patients receive cadonilimab with chemotherapy, or chemotherapy with or without nivolumab. All have HER2-negative gastric or gastroesophageal junction adenocarcinoma that is previously untreated and either unresectable or metastatic.
Why the comparison matters
For advanced gastric cancer the international standard is still chemotherapy, sometimes paired with a PD-1 inhibitor. In the United States, first-line PD-1 inhibitors are approved only for patients whose tumors test positive for PD-L1. NCCN and ESMO guidelines lean toward nivolumab-based regimens when the PD-L1 score (CPS) is 5 or higher.
Studies including CheckMate 649 found the benefit of a PD-1 inhibitor plus chemotherapy is greater in patients with high PD-L1 expression. Patients with low expression have fewer good options, which Akeso describes as a significant unmet need worldwide.
The new trial is designed to test the drug in patients from different geographic and ethnic backgrounds.
The people running it
Four principal investigators co-lead the study. They are Dr. Yelena Y. Janjigian, chief of the Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center; Professor Markus Möhler of Johannes Gutenberg University Mainz; and Professors Jiafu Ji and Lin Shen of Peking University Cancer Hospital. Janjigian, Möhler and Shen were all investigators on CheckMate 649, the trial that established nivolumab plus chemotherapy as a first-line option.
What earlier data show
Cadonilimab already has results in this disease. In an advanced gastric and gastroesophageal junction trial, adding it to XELOX chemotherapy lifted median overall survival to 13.9 months, against 11.1 months for placebo plus XELOX. Updated two-year data from Akeso put median overall survival at 17.41 months and median progression-free survival at 9.2 months.
The most common side effects reported with cadonilimab and chemotherapy were nausea (72%), vomiting (60%), neutropenia (51%) and leukopenia (45%). A cost-effectiveness analysis of the combination as first-line treatment for HER2-negative disease concluded it was not cost-effective.
A separate Phase 2 trial is testing cadonilimab with FLOT chemotherapy in adults whose HER2-negative stomach or junction cancer is locally advanced but can still be removed by surgery. People with any of these conditions should talk to their doctor about treatment options.
Sources
- Akeso Announces First Patient Enrolled in Global Phase III Trial of Cadonilimab Versus Nivolumab in First-Line Gastric Cancer
- A Study of Cadonilimab Combined With Chemotherapy in People With Gastric or Gastroesophageal Junction Cancer
