Efficacy and Safety of Cadonilimab Combined with Chemotherapy for Gastric or Gastroesophageal Junction Adenocarcinoma: A Single-Arm Meta-Analysis

Likun Yang¹Jiaxin Li²Xi Mo Wang^2*Xiangyang Yu^3*Zhengcun Pei^1*

• ¹Medical School, Tianjin University, Tianjin, China
• ²Tianjin Third Central Hospital, Tianjin, China
• ³Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

Background: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become an important area of clinical investigation in the gastric cancer (GC) and gastroesophageal junction cancer (GEJC). In recent years, bispecific antibody therapies have been increasingly explored, including cadonilimab, a programmed death-1/cytotoxic T-lymphocyte–associated antigen 4 (PD-1/CTLA-4) bispecific antibody. Several phase II studies have reported early signals of antitumor activity with cadonilimab, prompting clinical interest in this strategy. However, treatment outcomes vary across studies, and a systematic assessment of the efficacy and safety of cadonilimab plus chemotherapy remains limited. This study aimed to evaluate the efficacy and safety profile of cadonilimab in combination with chemotherapy for gastric adenocarcinoma and gastroesophageal junction adenocarcinoma (G/GEJ adenocarcinoma) through a single-arm meta-analysis. Methods: A systematic search was conducted in PubMed, Embase, the Cochrane Library, Web of Science, and ClinicalTrials.gov to identify eligible studies published up to July 20, 2025. A single-arm meta-analysis was performed to pool and evaluate the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), pathological complete response (pCR), and the incidence of grade ≥3 treatment-related adverse events (TRAEs). Results: A total of four clinical studies involving 182 patients were included. The pooled estimates were an ORR of 57% (95% CI: 48%–66%), a DCR of 97% (95% CI: 84%–100%), a pCR of 23% (95% CI: 12%– 35%), and a median PFS of 7.98 months (95% CI: 6.38–9.57). The overall incidence of grade ≥3 TRAEs was 35% (95% CI: 7%–63%). In subgroup analyses, the incidence of grade ≥3 TRAEs appeared lower in the neoadjuvant setting than in the first-line setting (29% [95% CI: 28%–40%] vs 53% [95% CI: 45%– 60%]). The most frequently reported adverse events included nausea (72%), vomiting (60%), neutropenia (51%), and leukopenia (45%). Conclusions: Based on available early-phase evidence, cadonilimab plus chemotherapy showed antitumor activity with a manageable safety profile in G/GEJ adenocarcinoma. Further large-scale, high-quality randomized controlled trials are needed to validate these findings and define the optimal treatment strategy.