A Phase III clinical study published in Nature Medicine reveals that cadonilimab, a PD-1/CTLA-4 bispecific antibody developed by Akeso, Inc., in combination with oxaliplatin and capecitabine, significantly improves overall survival in patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. The COMPASSION-15/AK104-302 study's findings, initially presented at the 2024 American Association for Cancer Research (AACR) Annual Meeting, have led to the approval and clinical use of cadonilimab as a first-line treatment option since September 2024.
The study's data indicate that cadonilimab, combined with chemotherapy, provides notable overall survival benefits for advanced gastric cancer patients, irrespective of PD-L1 expression levels. The overall survival hazard ratio (OS HR) was 0.62, demonstrating a significant reduction in the risk of disease-related death. Even in patients with low or negative PD-L1 expression, the cadonilimab regimen showed a meaningful survival benefit (OS HR 0.70), addressing a critical unmet need in this subgroup where PD-1 monoclonal antibody treatments have shown limited efficacy.
Addressing Unmet Needs in Gastric Cancer Treatment
Gastric cancer remains a significant global health challenge, with nearly one million new cases annually. In China, it accounts for approximately half of these cases and deaths. For patients ineligible for surgery or with metastatic disease, immunotherapy using PD-1/L1 monoclonal antibodies has shown some success in first-line treatment. However, survival benefits remain limited, particularly for the 88% of patients with HER2-negative tumors. Cadonilimab combination therapy aims to provide a more effective treatment option for a broader range of patients.
Clinical Significance and Ongoing Research
Professor Ji Jiafu from Peking University Cancer Hospital, a principal investigator in the COMPASSION-15 study, emphasized that cadonilimab combination therapy has substantially increased the objective response rate and overall survival while reducing disease-related mortality. He noted the significance of the survival benefits observed in patients with both high and low/negative PD-L1 CPS expression.
Professor Shen Lin, also from Peking University Cancer Hospital, highlighted that cadonilimab addresses the limitations of single-target immunotherapy by leveraging the synergistic mechanism of dual immune checkpoint inhibition. A Phase III clinical study (AK109-301) is underway, evaluating cadonilimab combined with pulocimab (AK109, VEGFR-2) for treating advanced gastric cancer that has progressed after PD-1/L1 inhibitor plus chemotherapy, with the hope of improving outcomes in second-line therapy.
Akeso's Broader Clinical Strategy
Akeso is currently investigating cadonilimab in over 23 clinical studies across 16 indications, including gastric, lung, liver, cervical, and pancreatic cancers. Besides the approved indications for recurrent/metastatic cervical cancer and first-line gastric cancer, cadonilimab is undergoing five Phase III clinical trials for liver cancer, non-small cell lung cancer, and gastric cancer. These studies aim to demonstrate the drug's efficacy across diverse populations, regardless of PD-L1 expression levels, potentially establishing cadonilimab as a cornerstone in next-generation cancer immunotherapy.
