Akeso Biopharma has announced the enrollment of the first patient in its Phase III clinical trial, AK112-309, a randomized, controlled, multicenter study. The trial is evaluating the efficacy and safety of ivonescimab, a PD-1/VEGF bispecific antibody, in combination with chemotherapy, as a first-line treatment for advanced biliary tract cancers (BTC). The comparator arm will receive durvalumab, a PD-L1 inhibitor, combined with chemotherapy.
This Phase III trial represents the sixth registrational study for ivonescimab, with a PD-1/L1 monoclonal antibody as the comparator. Biliary tract cancers, which include malignancies of the bile ducts and gallbladder, are often diagnosed at advanced stages, leading to poor prognosis with survival typically less than one year. While PD-1/L1 inhibitors combined with chemotherapy are approved as a first-line treatment, the overall survival benefit has been limited, particularly for patients with gallbladder cancer.
Promising Phase II Data
Previous Phase II clinical trial results of ivonescimab in combination with chemotherapy for first-line treatment of BTC, presented at the 2024 ASCO Annual Meeting, demonstrated significant antitumor activity and a manageable safety profile. Key findings from the Phase II study included:
- An objective response rate (ORR) of 63.6%, with gallbladder cancer patients showing a higher ORR of 77.8%.
- 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 also exhibiting a median OS of 16.8 months.
At the time of the analysis, the median follow-up time 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.
Trial Design and Objectives
The AK112-309 trial's primary endpoint is overall survival (OS). This Phase III study aims to determine if the ivonescimab regimen can offer a superior survival benefit compared to the durvalumab regimen in this patient population with limited treatment options.
"The initial positive clinical data from the ivonescimab regimen indicates a possible advancement in the therapeutic landscape for these challenging malignancies," according to Akeso Biopharma.
About Ivonescimab
Ivonescimab (AK112/SMT112) is a novel, first-in-class PD-1/VEGF bispecific immunotherapy drug independently developed by Akeso. It has already received marketing approval in China for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC) after EGFR TKI treatment failure. Akeso is currently conducting multiple clinical trials of ivonescimab across 17 indications, including gastrointestinal cancer, hepatocellular carcinoma, and colorectal cancer.
