U.S. trial tests ivonescimab for advanced biliary tract cancer

The ECOG-ACRIN Cancer Research Group has announced a randomized, registration-enabling phase 2/3 clinical trial to evaluate ivonescimab combined with chemotherapy as first-line treatment for patients with advanced biliary tract cancer in the United States. The study, EA2251 (NCT07765433), will compare ivonescimab plus gemcitabine and cisplatin with pembrolizumab or durvalumab plus the same chemotherapy. Overall survival is the primary endpoint, and clinical trial sites are expected to activate EA2251 in the fourth quarter of 2026.

The announcement follows reported results from HARMONi-GI1, a randomized phase 3 trial conducted in China and sponsored by Akeso, which developed ivonescimab. Akeso reported in August 2026 that ivonescimab plus chemotherapy improved overall survival compared with durvalumab plus chemotherapy at an interim analysis. The trial also met its key secondary endpoints for progression-free survival and objective response rate. Detailed results were scheduled for presentation on October 25 as a late-breaking Presidential Symposium abstract at the European Society for Medical Oncology 2026 Congress. The Chinese study provides the stated rationale for testing ivonescimab in a U.S. population, but those reported results do not establish efficacy in American patients.

EA2251 will enroll people with advanced biliary tract cancer and assess ivonescimab, an investigational bispecific antibody designed to target PD-1 and VEGF. PD-1 blockade is intended to support antitumor immune activity, while VEGF blockade is associated with anti-angiogenic effects. Ivonescimab is designed to combine these actions in a single molecule and to display cooperative binding, including higher affinity to PD-1 in the presence of VEGF. The drug is not approved in the United States. Besides overall survival, EA2251 will measure progression-free survival, objective response rate, duration of response, disease control rate and safety. The investigators designed the study to generate evidence that could support a submission to the U.S. Food and Drug Administration seeking approval of ivonescimab plus chemotherapy for advanced biliary tract cancer.

The comparator regimens reflect the first-line treatment framework established in the United States. Gemcitabine and cisplatin became the standard first-line chemotherapy for advanced biliary tract cancer more than a decade ago. Results from the phase 3 TOPAZ-1 and KEYNOTE-966 trials, published in 2022 and 2023, respectively, established the benefit of adding durvalumab or pembrolizumab to that chemotherapy. The announcement nevertheless describes prognosis as poor and identifies a need for better options. Biliary tract cancer is a group of rare, aggressive gastrointestinal cancers that includes gallbladder cancer and intrahepatic, perihilar and distal cholangiocarcinoma. These cancers may cause few clear symptoms in their early stages and are therefore often diagnosed after the disease has spread, when curative surgery may no longer be possible.

EA2251 will be conducted through the National Cancer Institute’s National Clinical Trials Network, with participation from Alliance for Clinical Trials in Oncology, NRG Oncology and SWOG Cancer Research Network. This national collaboration is intended to support recruitment across thousands of U.S. clinical sites, an important advantage for enrolling a large trial in a rare cancer. The National Cancer Institute, part of the National Institutes of Health, is funding the study. Summit Therapeutics, which is developing ivonescimab in the United States and other countries through a partnership agreement with Akeso, will supply the drug and provide financial support under a collaboration agreement with ECOG-ACRIN. The current announcement describes a planned trial and its methods; it does not provide results showing whether ivonescimab improves survival, progression-free survival or response in the U.S. population.

Subject of Research: Randomized phase 2/3 trial of ivonescimab plus chemotherapy for advanced biliary tract cancer

Article Title: ECOG-ACRIN announces a national trial of ivonescimab for first-line treatment of advanced biliary tract cancer

Article References: ECOG-ACRIN announces a national trial of ivonescimab for first-line treatment of advanced biliary tract cancer. Original publication (Bibliographic details unavailable.)

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Keywords: biliary tract cancer, ivonescimab, phase 2/3 trial, PD-1, VEGF, chemoimmunotherapy, overall survival, ECOG-ACRIN, National Cancer Institute, announces, national, trial