Akeso Starts Phase 3 Ivonescimab Combo Trial for Biliary Tract Tumors

HONG KONG, Oct. 31, 2024 — Akeso Biopharma has successfully enrolled the first participant in the AK112-309 study, a randomized, controlled, multicenter Phase III registration trial for biliary tract tumors. This study seeks to evaluate the efficacy of the ivonescimab combination regimen, a PD-1/VEGF bispecific antibody developed by Akeso, against the durvalumab (PD-L1) combination regimen in the first-line treatment of advanced biliary tract cancers (BTC). The primary endpoint for this trial is overall survival (OS).

The AK112-309 study is the sixth registrational Phase III clinical trial involving ivonescimab, with a PD-1/L1 monoclonal antibody as the comparator. This reflects Akeso's dedication to pushing forward cancer immunotherapy and establishing a global standard of care in cancer treatment. It also highlights Akeso's strategic clinical development approach aimed at maximizing the number of cancer patients worldwide who can benefit from their product portfolio.

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

In this Phase II study, the investigator-assessed objective response rate (ORR) was 63.6%, with an even higher ORR of 77.8% for patients with gallbladder cancer. The disease control rate (DCR) was observed to be 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%. Specifically, patients with gallbladder cancer showed a median OS of 16.8 months. At the time of analysis, the median follow-up period was 13.8 months. Participants 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.

Biliary tract cancers, originating from the bile ducts and gallbladder, are a highly heterogeneous group of malignancies with a poor prognosis. At diagnosis, approximately half 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 combined with chemotherapy have been approved for first-line treatment of advanced biliary tract cancer, the overall survival benefit remains limited, particularly for gallbladder cancer patients. The initial positive clinical data from the ivonescimab regimen suggest a potential advancement in therapeutic options for these challenging cancers.

Ivonescimab, also known as AK112 or SMT112, is a novel global first-in-class PD-1/VEGF bi-specific immunotherapy drug developed independently by Akeso. In Summit Therapeutics' licensed territories, including the United States, Canada, Europe, Japan, Central America, South America, the Middle East, and Africa, ivonescimab is referred to as SMT112. The NMPA has granted marketing approval for ivonescimab for treating EGFR mutated locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) patients who have progressed after EGFR TKI treatment. Currently, ivonescimab's first indication has been approved in China, with Akeso conducting six registrational trials against anti-PD-1/L1 therapies. Akeso is also conducting multiple clinical trials for ivonescimab across 17 indications, including gastrointestinal cancer, hepatocellular carcinoma, and colorectal cancer.

Akeso is a prominent biopharmaceutical company focused on the research, development, manufacturing, and commercialization of innovative biological medicines. Established in 2012, Akeso has developed a comprehensive end-to-end drug development platform (ACE Platform) and bi-specific antibody drug development technology (Tetrabody) as its core. With a GMP-compliant manufacturing system and an advanced commercialization system, Akeso has grown into a globally competitive biopharmaceutical company. Akeso is working on a robust pipeline of over 50 innovative assets in fields such as cancer, autoimmune disease, inflammation, metabolic disease, and other major diseases. With 22 candidates in clinical trials and multiple drugs commercially available or under regulatory review, Akeso aims to develop first-in-class and best-in-class new drugs, providing affordable therapeutic antibodies and continuously creating commercial and social value.