Akeso Biopharma (9926.HK) is pleased to announce the successful enrollment of the first patient in the HARMONi-GI-01/AK112-309 study, a randomized, controlled, multicenter Phase III registration study for biliary track tumor. This trial is designed to compare the ivonescimab combined regimen, a PD-1/VEGF bispecific antibody internally developed by Akeso, with the durvalumab (PD-L1) combined regimen for the first-line treatment of advanced biliary tract cancers (BTC). The primary endpoint of the AK112-309 study is overall survival (OS).

This study represents the sixth registrational Phase III clinical trial featuring ivonescimab, with a PD-1/L1 monoclonal antibody as the comparator. It underscores Akeso's commitment to advancing the field of cancer immunotherapy and establishing a global standard of care for cancer treatment. Furthermore, it highlights Akeso's capability to maximize the number of cancer patients globally that can benefit from its product portfolio through a strategic approach to clinical development.

Previously, the positive results from a Phase II clinical study of ivonescimab in combination with chemotherapy for the first-line treatment of BTC were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The findings demonstrated that the ivonescimab regimen exhibits significant antitumor activity and a good safety profile in BTC.

• The objective response rate (ORR), as assessed by investigators, was 63.6%, with an ORR of 77.8% specifically for patients with gallbladder cancer. The disease control rate (DCR) reached 100%.
• The median progression-free survival (PFS) was 8.5 months, with a 6-month PFS rate of 84.4%.
• Furthermore, the median overall survival (OS) was 16.8 months, with a 9-month OS rate of 81.8%. Notably, patients with gallbladder cancer exhibited a median OS of 16.8 months.

At the time of the analysis, the median follow-up time was 13.8 months. The study included patients with a median age of 65.3 years, of whom 81.8% had an ECOG performance status of 1. All enrolled patients are presented with unresectable tumors, and 40.9% were diagnosed with gallbladder cancer.

Biliary tract malignancies, originating from the bile ducts and gallbladder, represent a group of highly heterogeneous cancers associated with a poor prognosis. At the time of diagnosis, approximately 50% of biliary tract cancer patients are already in advanced stages, often with a survival period of less than one year. Although PD-1/L1 inhibitors in combination with chemotherapy have been approved as a first-line treatment for advanced biliary tract cancer, the overall survival benefit has been limited, particularly for patients with gallbladder cancer. The initial positive clinical data from the ivonescimab regimen indicates a possible advancement in the therapeutic landscape for these challenging malignancies.