Efficacy and safety of cadonilimab in patients with MSI-H/dMMR locally advanced or metastatic gastrointestinal malignancies: A real-world retrospective study.

2623 Background: Immunotherapies targeting PD-1 and CTLA-4 have emerged as promising therapeutic strategies for gastrointestinal malignancies (GIM), particularly those dMMR or MSI-H phenotypes. Cadonilimab, a novel bispecific antibody co-targeting PD-1 and CTLA-4, has showed potent anti-tumor effect across multiple cancer types. This real-world retrospective study systematically evaluated the efficacy and safety of cadonilimab in patients with MSI-H/dMMR locally advanced or metastatic GIM. Methods: This study retrospectively included patients with MSI-H/dMMR unresectable locally advanced or metastatic GIM who administered cadonilimab(6 mg/kg Q2W) since November 2022 in The Affiliated Hospital of Qingdao University. The primary endpoint was ORR as assessed by investigators per RECIST v1.1. Secondary endpoints included DCR, PFS, DoR, safety profile, and exploratory biomarker analysis (interleukins [IL-2, IL-6, IL-8, IL-10]) was performed on blood samples collected at baseline and before each treatment cycle. Results: As of November 7, 2025, a total of 21 patients were enrolled. The median follow-up duration was 19.4 months. The ORR was 76.19% and DCR was 100%. Median PFS and median DoR were not reached. The 12-month PFS rate was 74.9% (95% CI, 49.6%-88.8%) and 18-month PFS rate was 68.1% (95% CI, 41.6%-84.5%). Among 14 gastric cancer (GC) patients, ORR was 78.57% (5 CR, 6 PR), median PFS was not reached, 12-month PFS rate was 77.9% (95% CI, 58.6%-100%), and 18-month PFS rate was 68.2% (95% CI, 46.3%-100%). The ORR of GC treated in 1 st line was 80%, 4 achieved CR (40%). Among 7 colorectal cancer (CRC) patients, ORR was 71.43% (2 CR, 3 PR), median PFS was not reached, 12-month PFS rate was 71.4% (95% CI, 49.6%-88.8%), and 18-month PFS rate was 71.4% (95% CI, 29.4%-91.9%); the ORR of 1 st line treatment was 83.33%. By metastatic site: ORR was 85.71% in patients with peritoneal metastasis and 100% in those with pelvic metastasis. Notably, one patient achieved pCR after cadonilimab conversion therapy, and another patient receiving cadonilimab as fourth-line monotherapy achieved PFS of 25.4 months. As of data cutoff, 5 patients remained on treatment. Regarding safety, 33.33% of patients experienced grade 1-2 immune-related adverse events (irAEs), and 4.76% had grade ≥3 irAEs. No treatment discontinuation due to adverse events. Exploratory biomarker analysis showed that ORR was 90.91% in patients with high IL-2 expression, 91.67%,92.86% and 81.82% in patients with normal IL-6, IL-8 and IL-10 levels, respectively. Conclusions: Cadonilimab demonstrates potent and durable anti-tumor activity with a favorable safety profile in MSI-H/dMMR locally advanced or metastatic GIM. Additionally, interleukins may serve as potential predictive biomarkers for cadonilimab efficacy, providing insights for precision medicine in this patient population.