Neoadjuvant SOX combined with cadonilimab (AK104) for PD-L1 negative upper GC/GEJC patients

BackgroundGastric cancer (GC) remains a significant global health challenge, characterized by late diagnosis and limited treatment efficacy, leading to high mortality rates. Despite advancements in treatment, survival outcomes for patients in advanced stages remain poor. Recent evidence supports the S-1 plus oxaliplatin (SOX) chemotherapy regimen, along with the anti-PD-1 monoclonal antibodies to improve patient outcomes. Nonetheless, the efficacy of these treatments varies across different levels of Programmed Death-Ligand 1 (PD-L1) expression, underscoring the necessity for innovative approaches. Cadonilimab (AK104), a PD-1/CTLA-4 bispecific antibody, has demonstrated promise in PD-L1 negative populations, suggesting a potential new direction for therapy in upper gastric/gastroesophageal junction cancer (GEJC).Trial designThis prospective, single-arm, single-center Phase II trial aims to enroll 30 patients to evaluate the safety and efficacy of the SOX regimen combined with Cadonilimab (AK104) as neoadjuvant therapy for patients with PD-L1 negative (CPS<1) locally advanced upper GC/GEJC. The key eligibility criteria include a clinical staging of cT2-4aN0-3M0, tumor location in the upper third of the stomach, non-Her-2 positivity, and PD-L1 negativity (CPS < 1). Eligible patients will undergo four cycles of combined SOX and Cadonilimab (AK104) treatment. S-1 is administered orally twice daily, with doses adjusted based on body surface area (40 mg/day for <1.25 mˆ2, 50 mg/day for 1.25–1.5 mˆ2, and 60 mg/day for ≥1.5 mˆ2), from Day 1 to Day 14, followed by a rest week, forming a 3-week cycle. Oxaliplatin is administered intravenously over 2 hours at 130 mg/mˆ2 on Day 1 of each cycle. Cadonilimab (AK104) is given at 10 mg/kg, every three weeks per cycle. The primary endpoint is the pathological complete response rate, with secondary endpoints including major pathological response rate, objective response rate, disease control rate, R0 resection rate, 5-year overall survival rate, and progression-free survival rate. Safety and tolerability assessments will include the postoperative complication rate and adverse event rate. As of March 14, 2024, 5 patients have been recruited.Clinical trial identificationChiCTR2400079586.Legal entity responsible for the studyThe authors.FundingAkeso Biopharma Co., Ltd.DisclosureAll authors have declared no conflicts of interest.