Akeso Biopharma has announced the enrollment of the first patient in its Phase 3 HARMONi-GI-01/AK112-309 study. This randomized, controlled, multicenter trial is evaluating ivonescimab, a PD-1/VEGF bispecific antibody, in combination with chemotherapy as a first-line treatment for advanced biliary tract cancers (BTC). The study compares this regimen to durvalumab (a PD-L1 inhibitor) combined with chemotherapy, with overall survival (OS) as the primary endpoint.
Advancing Treatment for Biliary Tract Cancers
Biliary tract cancers, which originate in the bile ducts and gallbladder, are a heterogeneous group of malignancies with poor prognosis. Approximately 50% of patients are diagnosed at an advanced stage, often with a survival period of less than one year. While PD-1/L1 inhibitors combined with chemotherapy have been approved as first-line treatments, the overall survival benefit has been limited, especially for gallbladder cancer patients. This trial aims to address this unmet need.
Promising Phase 2 Results
Prior to this Phase 3 trial, positive results from a Phase 2 clinical study of ivonescimab in combination with chemotherapy for first-line BTC treatment were presented at the 2024 ASCO Annual Meeting. The data demonstrated significant antitumor activity and a manageable safety profile.
Key findings from the Phase 2 study included:
- An objective response rate (ORR) of 63.6%, with 77.8% in gallbladder cancer patients.
- A disease control rate (DCR) of 100%.
- A median progression-free survival (PFS) of 8.5 months, with a 6-month PFS rate of 84.4%.
- A median overall survival (OS) of 16.8 months, with gallbladder cancer patients exhibiting a median OS of 16.8 months.
At the time of the analysis, the median follow-up was 13.8 months. The study population had a median age of 65.3 years, with 81.8% having an ECOG performance status of 1. All patients had unresectable tumors, and 40.9% were diagnosed with gallbladder cancer.
Ivonescimab: A Novel Bispecific Antibody
Ivonescimab (AK112/SMT112) is a first-in-class PD-1/VEGF bispecific immunotherapy drug developed by Akeso. It has already received marketing approval in China for EGFR-mutated non-squamous non-small cell lung cancer (NSCLC) patients who have progressed after EGFR TKI treatment. Akeso is currently conducting six registrational trials of ivonescimab against anti-PD-1/L1 therapies, covering 17 indications, including gastrointestinal cancer, hepatocellular carcinoma, and colorectal cancer. This Phase 3 trial represents the sixth registrational Phase III clinical trial featuring ivonescimab.
