Phase 3 trial of first-line cadonilimab plus chemotherapy for HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma

A phase 3 trial at 75 centers in China evaluated addition of the bispecific PD-1 and CTLA-4 directed antibody cadonilimab to chemotherapy for previously untreated unresectable locally advanced or metastatic G/GEJ-adenocarcinoma. Patients were randomized 1:1 to cadonilimab (n=305) or placebo (n=305) every 3 weeks, added to chemotherapy. At the first interim analysis, median duration of follow-up was 18.7 months. Median overall survival was 14.1 months with cadonilimab versus 11.1 months with placebo (HR 0.66; p<0.001), meeting the primary endpoint. The median progression-free survival was 7.0 months versus 5.3 months (HR 0.53; 95% CI 0.44-0.65). Among patients with a PD-L1 combined positive score ≥ 5, the median OS was 15.3 months versus 10.9 months (HR 0.58; 95% CI 0.41-0.82). The objective response rate was 65.2% versus 48.9% with median duration of response 8.8 months versus 4.4 months. Grade ≥ 3 treatment-related adverse events occurred in 65.9% of the cadonilimab group and 53.6% of the placebo group. The authors conclude that cadonilimab plus chemotherapy compared with placebo plus chemotherapy significantly improved overall survival with a manageable safety profile in patients with advanced G/GEJ adenocarcinoma.