Cadonilimab plus chemotherapy versus PD-1 inhibitor plus chemotherapy as first-line (1L) treatment for advanced gastric (G) or gastroesophageal junction (GEJ) cancer with PD-L1 CPS <5: A propensity-matched, retrospective cohort study.

407 Background: Although PD-1 inhibitors plus chemotherapy have been established as 1L treatment for advanced G/GEJ cancer, the survival benefit remains limited in those with PD-L1 CPS <5. Cadonilimab, the first PD-1/CTLA-4 bispecific antibody, in combination with chemotherapy significantly improved efficacy versus chemotherapy in previously untreated patients (pts) with G/GEJ cancer, especially in those with PD-L1 CPS <5 in the phase III COMPASSION-15 trial. However, there is no clinical study comparing cadonilimab and PD-1 inhibitors in this population. This study aimed to evaluate the efficacy and safety of cadonilimab plus chemotherapy versus PD-1 inhibitor plus chemotherapy as 1L treatment for advanced G/GEJ cancer with PD-L1 CPS <5 in a real-world setting. Methods: Pts with PD-L1 CPS <5 G/GEJ cancer who received 1L cadonilimab plus chemotherapy (cadonilimab group) or PD-1 inhibitor plus chemotherapy (PD-1 inhibitor group) were eligible from August 2022 to August 2024. Propensity score matching (PSM) was performed between the two groups to mitigate potential confounding variables. Demographic and clinical characteristics, treatment information, clinical outcomes, including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS), and safety were analyzed. Results: A total of 73 pts with PD-L1 CPS <5 G/GEJ cancer were enrolled, with 26 in the cadonilimab group and 47 in the PD-1 inhibitor group. After PSM, 26 pts from each group were included for analysis. At the data cutoff (February 28, 2025), the median follow-up was 11.0 months (mo, 95% CI: 8.3-15.3). The median OS was significantly longer in the cadonilimab group (14.3 mo, 95% CI: 11.5–17.0) than in the PD-1 inhibitor group (10.3 mo, 95% CI: 8.7–11.8), with a hazard ratio (HR) of 0.49 (95% CI: 0.26-0.93; P=0.025). The median PFS was 9.3 mo (95% CI: 7.9-10.6) in the cadonilimab group and 5.8 mo (95% CI: 5.0-6.7) in the PD-1 inhibitor group (HR=0.43; 95% CI: 0.23-0.80; P=0.006). Cadonilimab group also exhibited a numerically higher ORR (73.3% vs. 57.1%, P=0.45). The DCR was 100% in both groups. The incidence of adverse events (AEs) was comparable between the two groups with 92.3% in the cadonilimab group and 100% in the PD-1 inhibitor group. Grade 3-4 AEs were reported in 30.8% pts in the cadonilimab group and 15.4% pts in the PD-1 inhibitor group (P=0.25), with platelet count decreased (11.5% vs. 3.8%; P=0.47) being the most common. Conclusions: Compared to PD-1 inhibitor plus chemotherapy, cadonilimab plus chemotherapy significantly improved PFS and OS with a manageable safety profile as 1L treatment of advanced G/GEJ cancer with PD-L1 CPS <5, suggesting that cadonilimab plus chemotherapy could be considered a potential therapeutic option for this population.