First-line (1L) cadonilimab plus AK117 and chemotherapy (chemo) in advanced gastric or gastroesophageal junction cancer (GC/GEJC): Updated results from a phase 2 study.

e16040 Background: Cadonilimab (anti-PD-1/CTLA-4 bispecific antibody) plus chemo is approved in China for 1L treatment of advanced GC/GEJC based on the phase 3 COMPASSION-15 study. AK117 is a novel humanized IgG4 monoclonal antibody targeting CD47, a macrophage immune checkpoint enabling tumor cells to evade phagocytic immune destruction. We previously reported preliminary efficacy and safety data from a phase 2 study evaluating cadonilimab + AK117 + chemo in 1L GC/GEJC (Xia et al., ASCO 2023). Herein, we present updated results with extended follow-up. Methods: Eligible patients (pts) with previously untreated, advanced HER2-negative GC/GEJC received cadonilimab (10 mg/kg) and AK117 (45 mg/kg) plus oxaliplatin and capecitabine every 3 weeks. Primary endpoints were safety and objective response rate (ORR). Secondary endpoints included duration of response (DoR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS) and overall survival (OS). Results: As of the data cutoff (October 12, 2025), a total of 41 pts were enrolled, and the median follow-up was 23.8 mo. Median age was 64.5 years (range 39.8-74.8), 82.9% male, 78% ECOG PS 1, 97.6% with metastatic disease (51.2% with liver metastases). Regarding PD-L1 status, 19.5% had CPS ≥ 5 and 43.9% had CPS ≥ 1. In the ITT population, ORR was 75.6% (2 CRs 4.9%; 29 PRs 70.7%) and DCR was 95.1%. Median DoR was 9.5 mo (95% CI 4.7-15.1). Median PFS was 8.5 mo (95% CI 5.8-16.1) and median OS was 19.0 mo (95% CI 14.8-NE). PFS and OS outcomes were favorable regardless of PD-L1 expression (Table). In pts with PD-L1 CPS < 5, median PFS and OS were 8.5 mo (95% CI 5.5-10.8) and 18.8 mo (95% CI 12.0-26.6), respectively. In those with PD-L1 CPS ≥ 5, median PFS and OS were not reached, with a 24-mo OS rate of 62.5%. Grade ≥ 3 treatment-related adverse events (TRAEs) were reported in 22 pts (53.7%). The most common TRAEs of grade ≥ 3 were decreased platelet count (24.4%), decreased neutrophil count (12.2%), and anemia (7.3%). No treatment-related deaths were reported. Conclusions: Consistent with prior reports, cadonilimab combined with AK117 and chemo showed encouraging efficacy and manageable safety in first-line treatment of advanced GC/GEJC. Clinical trial information: NCT05235542 . ITT (N=41) CPS < 1(N=21) CPS ≥ 1(N=18) CPS < 5(N=31) CPS ≥ 5(N=8) ORR, % (95% CI) 75.6(59.7-87.6) 71.4(47.8-88.7) 83.3(58.6-96.4) 74.2(55.4-88.1) 87.5(47.3-99.7) DCR, % (95% CI) 95.1(83.5-99.4) 95.2(76.2-99.9) 100(81.5-100) 96.8(83.3-99.9) 100(63.1-100) Median PFS, mo (95% CI) 8.5(5.8-16.1) 8.5(4.6-16.3) 9.6(5.8-NE) 8.5(5.5-10.8) NR(6.1-NE) Median OS, mo (95% CI) 19.0(14.7-NE) 18.8(6.0-NE) 24.7(14.8-NE) 18.8(12.0-26.6) NR(10.0-NE) 24-mo OS rate, % (95% CI) 48.4(32.5-62.6) 41.9(20.9-61.7) 55.6(30.5-74.8) 44.5(26.6-60.9) 62.5(22.9-86.1)