Phase 3 cadonilimab PD-1×CTLA-4 bispecific antibody + CAPOX vs CAPOX ± nivolumab in 1L HER2-negative gastric/GEJ

Akeso’s randomized, double-blind, multi-regional Phase 3 trial (NCT07700979) tests whether adding cadonilimab—a PD-1 (CD279) and CTLA-4 dual-targeting bispecific antibody—improves overall survival versus a control strategy of CAPOX (oxaliplatin DNA-crosslinking platinum + capecitabine fluoropyrimidine that inhibits DNA synthesis) with or without nivolumab (Bristol Myers Squibb’s PD-1 monoclonal antibody), with matched placebos to maintain blinding. The population is first-line, HER2-negative, previously untreated unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma (ITT primary comparison). The commercial/scientific angle is “dual-checkpoint in one molecule” as an alternative to giving separate PD-1 plus CTLA-4 antibodies, while benchmarking against an established PD-1+chemo standard. Today’s care for HER2-negative metastatic gastric/GEJ commonly uses fluoropyrimidine/platinum chemotherapy with a PD-1 inhibitor (often nivolumab) when appropriate, with later-line options including taxanes, irinotecan, and VEGFR2 inhibition (ramucirumab) depending on region and access. This pivotal design effectively asks whether cadonilimab+CAPOX can outperform contemporary immunochemotherapy practice (and/or chemo alone) in a broad first-line population.