Akeso Biopharma has announced the enrollment of the first patient in the HARMONi-GI-01/AK112-309 study, a Phase 3 clinical trial evaluating ivonescimab in combination with chemotherapy as a first-line treatment for advanced biliary tract cancers (BTC). The randomized, controlled, multicenter study compares this regimen to durvalumab combined with chemotherapy.
The trial's primary endpoint is overall survival (OS). Biliary tract cancers, which originate in the bile ducts and gallbladder, are a heterogeneous group of aggressive malignancies with poor prognosis. Approximately 50% of patients are diagnosed at an advanced stage, with survival often less than one year.
Promising Phase 2 Data
Previously presented data from a Phase 2 clinical study of ivonescimab plus chemotherapy in first-line BTC demonstrated encouraging results. The objective response rate (ORR) was 63.6% as assessed by investigators, with gallbladder cancer patients showing a higher ORR of 77.8%. The disease control rate (DCR) reached 100%. Median progression-free survival (PFS) was 8.5 months, with a 6-month PFS rate of 84.4%. The median overall survival (OS) was 16.8 months, with gallbladder cancer patients exhibiting a median OS of 16.8 months. The median follow-up time for the Phase 2 study 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 presented with unresectable tumors, and 40.9% were diagnosed with gallbladder cancer.
Ivonescimab: A Novel Bispecific Antibody
Ivonescimab, also known as AK112 or SMT112, is a novel, global first-in-class PD-1/VEGF bispecific immunotherapy independently developed by Akeso. It has already received marketing approval in China for EGFR-mutated non-small cell lung cancer (NSCLC) that has progressed after EGFR TKI treatment. Akeso is currently conducting six registrational trials of ivonescimab versus anti-PD-1/L1 therapeutics, as well as multiple clinical trials across 17 indications, including gastrointestinal cancer, hepatocellular carcinoma, and colorectal cancer.
Addressing Unmet Needs in BTC
While PD-1/L1 inhibitors combined with chemotherapy have been approved as a first-line treatment for advanced BTC, the overall survival benefit has been limited, particularly for patients with gallbladder cancer. The initial positive clinical data from the ivonescimab regimen suggests a potential advancement in the therapeutic landscape for these challenging malignancies. This Phase 3 trial represents a significant step towards establishing a new standard of care and improving outcomes for patients with biliary tract cancers.
