Multicenter phase 1b-2 trial of cadonilimab plus chemotherapy for HER2-negative gastric or gastroesophageal junction adenocarcinoma

Cadonilimab is a bispecific antibody targeting PD-1 and CTLA-4. The multicenter phase 1b-2 COMPASSION-04 trial in China evaluated first-line cadonilimab plus chemotherapy for HER2-negative unresectable advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. There were no dose-limiting toxicities during the dose escalation in phase 1b; the recommended phase 2 dose was determined as 6 mg/kg every two weeks. The objective response rate was 52.1%, with complete respons in 4.3%. The median duration of response, progression-free survival, and overall survival were 13.73 months (95% CI 7.79-19.12), 8.18 months (6.67-10.48), and 17.48 months (12.35-26.55), respectively. Median OS in patients with PD-L1 CPS ≥ 5 was 20.32 months (95% CI 4.67-NE) while median OS in patients with PD-L1 CPS < 1 was 17.64 months (11.63-31.70). The authors conclude that first-line cadonilimab plus chemotherapy had promising activity and manageable safety among patients with HER2-negative unresectable advanced or metastatic G/GEL adenocarcinoma, regardless of PD-L1 expression.