Akeso, Inc. (9926.HK) ("Akeso" or the "Company") announced FDA approval to initiate COMPASSION-37/AK104-311 trial, a global multicenter Phase III trial in gastric cancer evaluating cadonilimab, a first-in-class PD-1/CTLA-4 bispecific antibody. The study will compare cadonilimab plus chemotherapy against chemotherapy with or without nivolumab as first-line treatment for HER2-negative, unresectable or metastatic gastric/gastroesophageal junction adenocarcinoma.

This is the second international registrational study for cadonilimab, following the ongoing trial in immunotherapy-resistant hepatocellular carcinoma. COMPASSION-37 represents a pivotal advancement in cadonilimab's global development and a concrete step in Akeso's worldwide strategy, reinforcing its leadership in next-generation immuno-oncology. The company remains committed to its dual-track approach of proprietary development and strategic collaboration, leveraging global resources to accelerate cadonilimab's international availability and expand accessible treatment options for patients worldwide.

Chemotherapy with or without PD-1 inhibitors, such as nivolumab, represents the international standard of care for advanced gastric cancer. However, the disease exhibits significant heterogeneity. While PD-1 treatment in combination with chemotherapy remains an effective treatment in many gastric cancer patients with high PD-L1 expression (CPS >5), its efficacy is markedly limited in gastric cancer patients with low PD-L1 expression (CPS <5) or negative PD-L1 expression (CPS <1). These low and negative PD-L1 patients constitute well more than half of the total gastric cancer patient population.

In 2024, the FDA narrowed the indication for all approved PD-1 inhibitors in the first-line treatment of advanced gastric cancer, restricting their use to PD-L1-positive patients. Authoritative guidelines, including those from the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO), also prioritize recommending nivolumab-based regimens for patients with PD-L1 CPS ≥5. This underscores that treating advanced gastric cancer in PD-L1 low-expressing and negative patients has become a globally recognized clinical challenge.

In 2024, based on the COMPASSION-15 study results, cadonilimab in combination with chemotherapy was approved in China for the first-line treatment of gastric cancer, demonstrating benefit across all patient populations, including both PD-L1 positive and negative subgroups.

COMPASSION-15 is the only global Phase III clinical study in first-line advanced gastric cancer to have demonstrated survival benefit across all patient populations, irrespective of PD-L1 expression status. In this trial, patients with low PD-L1 expression and those who were PD-L1-negative accounted for as high as 49.8% and 23% of the enrolled population, respectively, significantly exceeding proportions observed in historical studies of its kind. The robust representation of low and negative PD-L1 patients in the study and the effective treatment of these patients validates cadonilimab's broad-spectrum antitumor efficacy beyond PD-L1 dependency in gastric cancer.

Long-term follow-up data showed that cadonilimab plus chemotherapy significantly reduced the risk of death by 39% in the overall population compared to the control group (OS HR 0.61), regardless of PD-L1 status. In the PD-L1 CPS ≥5 subgroup, the reduction in mortality risk reached 51% (OS HR 0.49). Importantly, even among patients with low PD-L1 expression (CPS <5), a statistically significant 24% reduction in mortality risk was maintained (OS HR 0.76). These results were presented as an oral report at ESMO 2025. Earlier interim analysis data from the COMPASSION-15 study had been released as a prominent oral presentation at AACR 2024, with the full manuscript subsequently published in the Nature Medicine. These results highlight cadonilimab's potential to elevate the current standard of tumor immunotherapy and address clinical challenges unmet by single-target agents.