Hong Kong, August 20, 2025 — Akeso, Inc. (9926.HK) has announced the enrollment and dosing of the first patient in its pivotal Phase III clinical trial, AK104-310/COMPASSION-33, evaluating cadonilimab, a first-in-class PD-1/CTLA-4 bispecific antibody, in combination with chemotherapy for the perioperative treatment of resectable gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. This milestone marks a significant step forward in the development of innovative immunotherapy for gastric cancer, addressing a critical unmet medical need.

Science Significance

Cadonilimab’s dual targeting of PD-1 and CTLA-4 immune checkpoints represents a novel approach in cancer immunotherapy. Unlike traditional PD-1 inhibitors, cadonilimab’s bispecific design allows simultaneous inhibition of both pathways, enhancing anti-tumor activity. The COMPASSION-33 trial, the third Phase III study for cadonilimab in gastric cancer, aims to improve radical resection rates, reduce recurrence and metastasis risks, and enhance overall survival. Preliminary data suggest cadonilimab may offer superior efficacy and a more favorable safety profile compared to existing PD-1 therapies, particularly for patients with varying PD-L1 expression levels, including those with low or negative expression.

Regulatory Significance

The initiation of the COMPASSION-33 trial expands cadonilimab’s clinical scope from unresectable advanced gastric cancer, for which it is already approved in China, to resectable cases. This development aligns with global regulatory interest in perioperative immunotherapies, as no such regimens are currently approved worldwide. The trial’s outcomes could pave the way for regulatory submissions to expand cadonilimab’s indications, potentially setting a new standard for perioperative treatment in gastric cancer. Akeso’s prior success, with cadonilimab approved for advanced gastric cancer and cervical cancer, underscores its potential to meet stringent regulatory requirements.

Business Significance

For Akeso, the COMPASSION-33 trial strengthens its position as a leader in bispecific antibody development. Cadonilimab’s approval in China for first-line treatment of advanced gastric cancer has already demonstrated commercial success, generating 1.15 billion RMB in sales within its first 12 months on the market. Expanding its application to resectable gastric cancer could significantly broaden its market potential, addressing a larger patient population. Additionally, Akeso’s ongoing global trials, including those for hepatocellular carcinoma and non-small cell lung cancer, enhance its portfolio and attractiveness to investors and partners.

Patients’ Significance

Gastric cancer remains a major global health challenge, with approximately 500,000 new cases annually in China alone. The COMPASSION-33 trial offers hope for patients with resectable G/GEJ adenocarcinoma by potentially improving surgical outcomes and reducing recurrence risks. Cadonilimab’s efficacy across all PD-L1 expression levels, including low and negative, is particularly significant, as it addresses a critical gap in current treatments where PD-1 inhibitors often show limited benefit for PD-L1-negative patients. This could translate to improved survival and quality of life for a broader patient population.

Policy Significance

The absence of approved perioperative immunotherapy regimens globally highlights a policy gap in addressing unmet needs in gastric cancer treatment. The COMPASSION-33 trial could influence health policy by providing evidence to support the integration of bispecific antibodies into standard care protocols. Positive outcomes may prompt regulatory bodies and healthcare systems to prioritize funding and access to innovative immunotherapies, potentially reshaping treatment guidelines and reimbursement policies for gastric cancer worldwide.

The dosing of the first patient in the COMPASSION-33 trial marks a pivotal moment in the fight against gastric cancer. By leveraging cadonilimab’s unique bispecific mechanism, Akeso is poised to redefine perioperative treatment standards, offering hope to patients and potentially transforming clinical practice. As the trial progresses, the global medical community will closely watch its outcomes, which could herald a new era in immunotherapy for resectable gastric cancer.