First-Line Cadonilimab Plus Chemo Wins Approval in China for Advanced Gastric/GEJ Adenocarcinoma

China’s National Medical Products Administration (NMPA) has approved cadonilimab in combination with fluoropyrimidine and platinum-based chemotherapy for first-line treatment of patients with locally advanced, unresectable or metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma.¹

The regulatory decision was supported by data from the phase 3 COMPASSION-15/AK104-302 trial (NCT05008783), which showed that in the intention-to-treat (ITT) population, the median overall survival (OS) was 15.0 months (95% CI, 12.3-19.3) for those treated with cadonilimab plus oxaliplatin and capecitabine (Xelox; n = 305) vs 10.8 months (95% CI, 9.8-12.0) for those given placebo plus chemotherapy (n = 305; HR, 0.62; 95% CI, 0.50-0.78; P < .001).²

In patients with a PD-L1 combined positive score (CPS) of at least 5, the median OS was not reached (NR; 95% CI, 11.4–not evaluable) for the cadonilimab arm (n = 116) vs 10.6 months (95% CI, 8.6-12.6) for the placebo arm (n = 140; HR, 0.56; 95% CI, 0.39-0.80; P < .001). In subgroup of patients with a PD-L1 CPS of less than 5, the median OS for the cadonilimab arm (n = 157) and placebo arm (n = 147) was 14.8 months (95% CI, 11.6-18.6) and 11.1 months (95% CI, 10.1-13.0), respectively (HR, 0.70; 95% CI, 0.51-0.95; P = .011).

“We are delighted by the successful approval of cadonilimab combination therapy for the first-line treatment of advanced gastric cancer [in China],” Shen Lin, MD, of Peking University Cancer Hospital and principal investigator of COMPASSION-15, stated in a news release.¹ “This regimen offers significant advantages over current immunotherapy options in clinical practice, providing a superior choice not only for patients with high PD-L1 expression but also for those with low or negative PD-L1 expression, who previously lacked effective treatment options.”

The randomized, double-blind COMPASSION-15 trial enrolled patients between 18 and 75 years of age with histologically confirmed locally advanced/unresectable or metastatic gastric/GEJ adenocarcinoma who received no prior systemic therapy.² Patients were required to have an ECOG performance status of 0 or 1, a measurable tumor lesion per RECIST 1.1 criteria, and a life expectancy of at least 3 months.

Patients were randomly assigned 1:1 to receive cadonilimab at 10 mg/kg plus chemotherapy once every 3 weeks for up to 6 cycles, followed by cadonilimab alone at 10 mg/kg once every 3 weeks; or placebo plus chemotherapy once every 3 weeks for up to 6 cycles, then placebo alone once every 3 weeks.

OS in the ITT population served as the trial’s primary end point. Secondary end points included OS in patients with a PD-L1 CPS of at least 5; investigator-assessed progression-free survival (PFS), overall response rate, disease control rate, and duration of response in the ITT population; and safety.

Additional data showed the median PFS in the ITT population was 7.0 months (95% CI, 6.4-8.4) in the cadonilimab arm vs 5.3 months (95% CI, 4.5-5.6) in the placebo arm (HR, 0.53; 95% CI, 0.44-0.65; P < .001).

Regarding safety, any-grade treatment-related adverse effects (TRAEs) occurred in 99.0% of patients in the cadonilimab arm vs 97.4% of patients in the placebo arm. The respective rates of grade 3 or higher TRAEs were 65.9% and 53.6%. Any-grade and grade 3 or higher serious TRAEs were reported at respective rates of 38.4% and 30.5% in the cadonilimab group. These rates were 25.7% and 21.7%, respectively, in the control arm. Any-grade TRAEs led to treatment discontinuation in 23.9% of patients in the cadonilimab arm vs 6.6% of patients in the placebo arm.

Cadonilimab was previously approved in China in June 2022 for use in patients with relapsed or metastatic cervical cancer that had progressed on or following platinum-based chemotherapy.³

References

1. Akeso's cadonilimab receives second indication approval from NMPA for first-line treatment of gastric/GEJ cancer in all-comers population. News release. Akeso. September 30, 2024. Accessed September 30, 2024. https://www.prnewswire.com/news-releases/akesos-cadonilimab-receives-second-indication-approval-from-nmpa-for-first-line-treatment-of-gastricgej-cancer-in-all-comers-population-302262242.html
2. Ji J, Shen L, Li Z, et al. Cadonilimab plus chemotherapy versus chemotherapy as first-line treatment for unresectable locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (COMPASSION-15): A randomized, double-blind, phase 3 trial. Presented at: 2024 AACR Annual Meeting; April 5-10, 2024; San Diego, CA. Abstract CT006.
3. Akeso’s cadonilimab (PD-1/CTLA-4), the first dual immune checkpoint inhibitor to treat cancer, approved for marketing in China. Akeso. News release. June 29, 2022. Accessed September 30, 2024. https://www.akesobio.com/en/media/akeso-news/20220629/