On January 22, 2025,《Nature Medicine》 published the results of the Akeso independently developed PD-1/CTLA-4 bispecific antibody cadonilimab in combination with oxaliplatin and capecitabine for the first-line treatment of unresectable locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma in a Phase III clinical study (COMPASSION-15/AK104-302). The results of the COMPASSION-15 study were previously orally presented at the 2024 American Association for Cancer Research (AACR) Annual Meeting.
This was a randomized, double-blind, placebo-controlled phase 3 study. Eligible patients were adults with untreated, unresectable, locally advanced or metastatic G/GEJ adenocarcinoma. Patients were randomized 1:1 to receive cadonilimab (10 mg kg−1 every 3 weeks) or placebo plus chemotherapy (every 3 weeks). The primary endpoint was overall survival (OS) in the intention-to-treat population (one-sided significance level, P = 0.025). Secondary endpoints included OS in patients with a PD-L1 combined positive score ≥5, progression-free survival, objective response rate, duration of response and safety. As of 18 August 2023, 610 patients from 75 study centers were randomized to cadonilimab (n = 305) or placebo (n = 305). With a median follow-up of 18.7 months, the cadonilimab group had a significantly longer median OS (14.1 versus 11.1 months; hazard ratio (HR) 0.66; 95% confidence interval (CI) 0.54–0.81; P < 0.001) than the placebo group. The primary endpoint was met. The median progression-free survival was 7.0 months versus 5.3 months (HR 0.53, 95% CI 0.44–0.65). The median OS in patients with a PD-L1 combined positive score ≥5 was 15.3 months versus 10.9 months (HR 0.58, 95% CI 0.41–0.82). The objective response rate was 65.2% versus 48.9% with a median duration of response of 8.8 months versus 4.4 months. Grade ≥3 treatment-related adverse events occurred in 65.9% of the cadonilimab group and 53.6% of the placebo group, and the most common were decreased platelet count, decreased neutrophil count and anemia. Most of the immune-related adverse events were grade 1 or 2. No new safety signals were observed. Cadonilimab plus chemotherapy significantly improved OS with a manageable safety profile in patients with advanced G/GEJ adenocarcinoma.
Cadonilimab injection is a novel, first-in-class PD-1/CTLA-4 bi-specific immunotherapy drug in-house developed.On June 29th, 2022, Cadonilimab has been granted marketing approval by the NMPA of China for the treatment of relapsed or metastatic cervical cancer (R/M CC) patients who progressed on or after platinum-based chemotherapy. In September 2024，a new indication for cadonilimab has been approved for first-line treatment of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma，in combination with fluoropyrimidine and platinum-based chemotherapy. Currently, the new drug applications for Cadonilimab combined with platinum-based chemotherapy, with or without bevacizumab, for the first-line treatment of persistent, recurrent, or metastatic cervical cancer has been accepted by the CDE. Additionally, a series of clinical studies, including a phase III trial for adjuvant therapy in patients with a high risk of recurrence following curative resection of hepatocellular carcinoma, are being efficiently conducted.
At present, there are still many clinical trials of new anti-cancer technologies in China seeking patients. Consultation on new drugs and technologies, you can contact Beijing South Region Oncology Hospital International Department.
Phone Number：4008803716
Email：myimmnet@163.com
References
https://www.nature.com/articles/s41591-024-03450-4
Post time: Feb-21-2025