Cadonilimab receives second indication approval from NMPA for first-line treatment of gastric/GEJ cancer in all-comers population

This is the second indication approval for cadonilimab in China, following its initial approval for marketing in June 2022. The approval of the new indication for cadonilimab combination therapy for first-line treatment of gastric/GEJ cancer is based on the COMPASSION-15/AK104-302 study. In the COMPASSION-15 study, the proportion of patients with PD-L1 CPS  less than  5 and PD-L1 CPS less than 1 in the Intention-to-Treat (ITT) population reached 49.8% and 23%, respectively, which is significantly higher than the data disclosed in previous phase III studies of other immunotherapies for first-line treatment.

In November 2023, the interim analysis of the study achieved the primary endpoint of overall survival (OS). The results showed that the cadonilimab combination therapy significantly reduced the risk of death in advanced gastric cancer patients across all PD-L1 expression levels (including those with PD-L1 CPS  greater than 5 ), extending overall survival benefits and demonstrating notable advantages in objective response and long-term survival. Previous phase III trials of PD-1 inhibitors combined with chemotherapy showed limited or no clinical benefit for patients with low or negative PD-L1 expression.

The results of the COMPASSION-15 study were presented as an oral report at the 2024 AACR. In the ITT population, the median overall survival (mOS) for the cadonilimab regimen reached 15.0 months, compared to 10.8 months in the control group, extending overall survival by 4.2 months and reducing the risk of death by 38% (HR=0.62). In the PD-L1 CPS less than 5 group, the mOS for the cadonilimab regimen was 14.8 months, with a 30% reduction in the risk of death compared to the control group (11.1 months, HR=0.70). For the PD-L1 CPS greater han ≥5 group, the mOS had not yet been reached, but the risk of death was reduced by 44% compared to the control group (10.6 months, HR=0.56).

COMPASSION-15's principal investigator, Professor Ji Jiafu from Peking University Cancer Hospital, stated: “ The prognosis for advanced gastric cancer is poor. While currently approved immunotherapy options have improved efficacy compared to traditional chemotherapy, there remains significant potential for enhancement. The cadonilimab combination therapy has substantially increased the objective response rate and overall survival in the general population while reducing disease-related mortality. Remarkably, cadonilimab shows significant overall survival benefits not only in patients with high PD-L1 CPS expression but also in those with low or negative PD-L1 CPS expression.

The approval of cadonilimab as a first-line treatment effectively addresses the efficacy gap of PD-1/L1 monoclonal antibodies in patients with low or negative PD-L1 expression, providing a more comprehensive and effective immunotherapy option for advanced gastric cancer. This advancement benefits all patient populations and presents new opportunities for the global development of gastric cancer immunotherapy, carrying important clinical implications.

COMPASSION-15's principal investigator, Professor Shen Lin from Peking University Cancer Hospital, stated: “We are delighted by the successful approval of cadonilimab combination therapy for the first-line treatment of advanced gastric cancer. 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.Cadonilimab addresses the limitations of single-target immunotherapy and exemplifies the synergistic mechanism of dual immune therapy with "anti-PD-1 + anti-CTLA-4," thereby filling an important clinical gap in the treatment of advanced gastric cancer. Beyond first-line approval, the phase III clinical study (AK109-301) of cadonilimab combined with pulocimab (AK109, VEGFR-2) for treating advanced gastric cancer that has progressed after PD-1/L1 inhibitor plus chemotherapy has been initiated. There is currently a lack of effective standard treatments for patients with acquired resistance to immunotherapy, and we eagerly anticipate that this new combination regimen will yield improved results in second-line therapy for these patients, ultimately providing clinicians with more effective tools for cancer treatment.”