Phase 2 cadonilimab PD-1×CTLA-4 bispecific antibody plus FLOT in resectable gastric/GEJ cancer

This Memorial Sloan Kettering–sponsored Phase 2, single-arm perioperative study tests whether adding cadonilimab to FLOT can safely deepen pathologic responses in locally advanced, resectable, HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. Cadonilimab (AK104; from Akeso) is a bispecific monoclonal antibody that targets PD-1 (CD279) and CTLA-4 to enhance antitumor T-cell activity via dual checkpoint blockade. Participants receive neoadjuvant cadonilimab with FLOT (5-fluorouracil + leucovorin + oxaliplatin + docetaxel), then undergo curative-intent surgery, followed by adjuvant therapy per protocol. The commercial/scientific angle is bringing “dual-checkpoint” immunotherapy into the curative-intent window while retaining the widely used FLOT backbone, aiming to increase major pathologic response and R0 resection rates without unacceptable perioperative toxicity. For these patients today, care is perioperative chemotherapy with FLOT (or fluoropyrimidine/oxaliplatin regimens in some settings) followed by gastrectomy/esophagogastrectomy with lymphadenectomy; immunotherapy is more established in metastatic disease and is still being defined in the perioperative setting.