Cadonilimab Prolongs Survival in PD-L1–Low First-Line Gastric/GEJ Cancers

The addition of cadonilimab (Kaitanni) to chemotherapy extended survival among patients with PD-L1–low gastric and gastroesophageal junction (GEJ) cancers vs a PD-1 monoclonal antibody/chemotherapy regimen, according to findings from a retrospective cohort study presented at the 2026 ASCO Gastrointestinal Cancers Symposium.¹

Data revealed that after a median follow-up of 11.0 months (95% CI, 8.3-15.3), the median overall survival (OS) between the cadonilimab and PD-1 antibody arms was 14.3 months (95% CI, 11.5-17.0) vs 10.3 months (95% CI, 8.7-11.8), with an HR of 0.49 (95% CI, 0.26-0.93; P = .025). The median progression-free survival (PFS) was 9.3 months (95% CI, 7.9-10.6) vs 5.8 months (95% CI, 5.0-6.7) in the respective groups (HR, 0.43; 95% CI, 0.23-0.80; P = .006). The 6- and 12-month PFS rate estimates in the respective arms were 58.3% vs 34.6% and 25.0% vs 7.7%; the respective 6- and 12-month OS rate estimates were 65.4% vs 42.3% and 46.2% vs 23.1%.

Regarding response, the cadonilimab regimen displayed a numerically higher objective response rate (ORR) at 73.3% vs 57.1% with PD-1 inhibition (P = .45). The disease control rate (DCR) was 100% in both arms.

“Compared with PD-1 [inhibition] plus chemotherapy, cadonilimab plus chemotherapy significantly improved PFS and OS with a manageable safety profile as [a first-line] treatment of advanced [gastric]/GEJ cancer with PD-L1 combined positive score [CPS of less than] 5, suggesting that cadonilimab plus chemotherapy could be considered a potential therapeutic option for this population,” Duqin Zhao, of the Department of Hepatobiliary, Pancreatic, and Gastric Medicine at the University of Chinese Academy of Sciences of Zhejiang Cancer Hospital in Hangzhou, China, wrote in the presentation with study coinvestigators.¹

The cohort study enrolled patients with a PD-L1 CPS of less than 5 and randomly assigned them 1:1 to receive cadonilimab plus chemotherapy (n = 26) or PD-1 inhibition plus chemotherapy (n = 26) from August 2022 to August 2024. Patients eligible for enrollment included those with histologically confirmed unresectable locally advanced or metastatic disease and no prior receipt of systemic therapy for their disease.

Among the cadonilimab and PD-1 inhibitor groups, the mean age was 55.9 years (SD, 10.4) and 57.5 years (SD, 12.0), with 76.9% vs 61.5% of each having patients younger than 65 years of age. Most patients were female (57.7% vs 65.4%), had an ECOG performance status of 1 or 2 (73.1% vs 80.8%), and had a CPS of less than 1 (61.5% vs 57.7%). A total of 30.8% vs 23.1% had liver metastases, and 38.5% vs 38.5% had peritoneum metastases.

Clinical outcomes assessed in the study included ORR, DCR, PFS, OS, and safety. Propensity score matching was performed between each group to mitigate confounding variables.

Safety data revealed that the incidence of AEs between the 2 groups was comparable, with 92.3% of the cadonilimab and 100% of the PD-1 inhibitor group experiencing any-grade AEs. The incidence of grade 3 to 4 AEs was numerically higher in the cadonilimab group, at 30.8% vs 15.4% with PD-1 inhibition; however, the difference did not reach statistical significance (P = .25). The most common grade 3 or 4 AE was platelet count decreases, occurring in 11.5% vs 3.8% of the respective arms (P = .47).

According to a press release from the developer, Akeso, several prospective head-to-head phase 3 registration studies are assessing the efficacy of cadonilimab, including the phase 3 COMPASSION-37 study comparing cadonilimab plus chemotherapy with nivolumab (Opdivo) plus chemotherapy as a first-line treatment for advanced gastric cancer.² This trial was accepted for initiation by the FDA at the end of 2025.

References

1. Zhao D, Wu Z, Huang Y, et al. 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. J Clin Oncol. 2026;44(suppl 2):407. doi:10.1200/JCO.2026.44.2_suppl.407
2. Head-to-head real-world data: cadonilimab outperforms PD-1 inhibitors in first-line PD-L1-low gastric cancer. News release. Akeso. January 13, 2026. Accessed January 24, 2026. https://tinyurl.com/yffcj4nr