The ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) announced today that it will open 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 (BTC). The new study, EA2251 (NCT07765433), will test whether ivonescimab, an investigational bispecific antibody that targets PD-1 and VEGF, can improve survival beyond standard chemotherapy and immunotherapy. Clinical trial sites can expect to activate the study in the fourth quarter of 2026.
EA2251 follows reported results from HARMONi-GI1, a randomized phase 3 trial conducted in China and sponsored by Akeso, the inventors of ivonescimab. In August 2026, Akeso reported that ivonescimab plus chemotherapy improved overall survival compared with durvalumab plus chemotherapy at a prespecified interim analysis. The study also met its key secondary endpoints for progression-free survival and objective response rate. Detailed results are scheduled for presentation on October 25 as a Presidential Symposium late-breaking abstract at the European Society for Medical Oncology (ESMO) 2026 Congress.
EA2251 will evaluate ivonescimab combined with gemcitabine and cisplatin chemotherapy (GemCis) compared with pembrolizumab or durvalumab combined with GemCis in a U.S. population. Overall survival is the primary endpoint.
“The reported survival benefit with ivonescimab compared with durvalumab plus chemotherapy in China provides a compelling rationale for EA2251. Our national trial will test whether targeting both PD-1 and VEGF can improve overall survival beyond current first-line standard of care,” said lead investigator Deirdre J. Cohen, MD, MS . Dr. Cohen is an associate professor of medicine at the Icahn School of Medicine at Mount Sinai, director of the Gastrointestinal Oncology Program for the Mount Sinai Health System, and co-director of the Center of Excellence for Pancreatic Cancer at the Mount Sinai Tisch Cancer Center.
Secondary endpoints include progression-free survival, objective response rate, duration of response, disease control rate, and safety. The study is designed to generate evidence that could support a submission to the U.S. Food and Drug Administration seeking approval of ivonescimab plus chemotherapy for advanced BTC.
Biliary tract cancer comprises a group of rare, aggressive gastrointestinal cancers, including gallbladder cancer and intrahepatic, perihilar, and distal cholangiocarcinoma, which develop in the bile ducts. Because these cancers often cause few clear symptoms in their early stages, they are frequently diagnosed after the disease has spread, when curative surgery may no longer be an option.
GemCis became the standard first-line treatment for advanced BTC in the U.S. more than a decade ago. Results published in 2022 and 2023 from the phase 3 trials TOPAZ-1 and KEYNOTE-966, respectively, established the benefit of adding durvalumab or pembrolizumab to GemCis. However, prognosis remains poor, and there is a need for better treatment options.
Ivonescimab is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. By design, ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity to PD-1 when in the presence of VEGF. This design is intended to differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab is not approved in the United States.
EA2251 is funded by the National Cancer Institute (NCI), part of the U.S. National Institutes of Health. Summit Therapeutics Inc., which is developing ivonescimab in the U.S. and other countries through a partnership agreement with Akeso, will supply ivonescimab and provide financial support through a collaboration agreement with ECOG-ACRIN.
ECOG-ACRIN will conduct the study through the NCI’s National Clinical Trials Network, with participation from Alliance for Clinical Trials in Oncology, NRG Oncology, and SWOG Cancer Research Network. This national collaboration will support patient recruitment across thousands of U.S. clinical sites—an important advantage for a large trial in a rare cancer.
Investigators interested in opening EA2251 at their clinical site can learn more at ecog-acrin.org and clinicaltrials.gov ( NCT07765433 ).
About ECOG-ACRIN
The ECOG-ACRIN Cancer Research Group is one of the world’s leading scientific organizations, known for innovative multicenter clinical trials involving adults with cancer or at risk of developing it. Its expansive membership network includes over 1,400 hospitals and cancer centers across the United States and around the world, and nearly 21,000 researchers and advocates. Its research is funded primarily by the National Cancer Institute, part of the US National Institutes of Health. To learn more, visit www.ecog-acrin.org and follow us on X , Facebook , LinkedIn , YouTube , Instagram , and Bluesky , or call 215-789-3631.
Randomized controlled/clinical trial
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