Akeso's Ivonescimab Enters Phase 2/3 Biliary Tract Cancer Trial in US

Akeso announced on October 21, 2026, that Summit Therapeutics, its global partner for ivonescimab, has entered into a clinical trial collaboration with the ECOG-ACRIN Cancer Research Group to evaluate ivonescimab in a registration-enabling phase 2/3 study in biliary tract cancer (BTC).¹ Ivonescimab is a bispecific antibody that targets programmed cell death protein 1 (PD-1) and vascular endothelial growth factor (VEGF). The study, EA2251 (NCT07765433),² will compare ivonescimab plus chemotherapy with pembrolizumab (Keytruda) or durvalumab (Imfinzi) plus chemotherapy as first-line treatment for patients with advanced BTC.¹

"Biliary tract cancer is often diagnosed at an advanced stage, and despite recent progress, there is a need for more effective first-line options that can extend survival and improve disease control," said lead investigator Deirdre J. Cohen, MD, MS, 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, in a company press release.¹

US clinical trial site activations are expected to begin in the fourth quarter of 2026.¹

How does EA2251 fit into the ivonescimab development program?

EA2251 is the 7th international registrational phase 2/3 trial of ivonescimab and the second registrational phase 3 study of the drug in BTC.¹ Akeso reports that more than 18 phase 3 studies of ivonescimab are underway globally, including 7 head-to-head studies vs PD-1 or programmed cell death ligand 1 (PD-L1) therapies.¹

Maky Zanganeh, DDS, president and co–CEO of Summit, said in the release that "the sponsorship and conduct of this registration-enabling study by a leading cooperative oncology group underscores the scientific interest in evaluating ivonescimab in difficult-to-treat cancers, including BTC."¹

Summit holds exclusive rights to develop and commercialize ivonescimab in the United States, Canada, South America, Europe, the Middle East, Africa, and Japan under an agreement with Akeso valued at up to $5 billion.¹

What did the HARMONi-GI1 trial show?

The EA2251 collaboration follows the phase 3 HARMONi-GI1 (AK112-309) trial, which Akeso conducted in China. In August 2026, Akeso reported that HARMONi-GI1 met its primary end point at a prespecified interim analysis, with ivonescimab plus chemotherapy demonstrating a statistically significant overall survival (OS) benefit over durvalumab plus chemotherapy in first-line advanced BTC.³ The trial also met its key secondary end points of progression-free survival and objective response rate.³

Detailed HARMONi-GI1 results are scheduled for presentation during the Presidential Symposium at the European Society for Medical Oncology 2026 Congress on October 25, 2026.¹

Why is the comparator arm significant?

Durvalumab plus gemcitabine and cisplatin became a first-line standard in advanced BTC after the phase 3 TOPAZ-1 trial of 685 patients. In that trial, median OS was 12.8 months with the durvalumab regimen vs 11.5 months with placebo plus chemotherapy.⁴ By testing ivonescimab against pembrolizumab- or durvalumab-based regimens, EA2251 will compare the bispecific with current immunotherapy-based standards of care rather than with chemotherapy alone.¹

Ivonescimab is designed to combine PD-1 blockade with anti-angiogenic VEGF inhibition in a single molecule. It is approved in China for non–small cell lung cancer but is not approved in the US or Europe.³

What are the limitations?

US site activations for EA2251 have not yet begun, and the release did not disclose the study's target enrollment, chemotherapy backbone, primary end point, or timeline for results. HARMONi-GI1 was a single-region trial conducted in China, and its efficacy and safety data were generated, managed, and analyzed by Akeso.³ No hazard ratio, median survival, or safety data from HARMONi-GI1 have been publicly disclosed ahead of the October 25 presentation, and the results have not been peer reviewed.

References

1. Akeso. Akeso announces Summit Therapeutics and ECOG-ACRIN Cancer Research Group enter into Phase II/III clinical trial collaboration to evaluate ivonescimab in first-line biliary tract cancer. Press release. Published October 21, 2026. Accessed October 21, 2026. https://prnmedia.prnewswire.com/news-releases/akeso-announces-summit-therapeutics-and-ecog-acrin-cancer-research-group-enter-into-phase-iiiii-clinical-trial-collaboration-to-evaluate-ivonescimab-in-first-line-biliary-tract-cancer-302915469.html
2. Testing the addition of ivonescimab combined with standard chemotherapy compared to the usual chemotherapy and immunotherapy treatment for patients with advanced biliary tract cancer. ClinicalTrials.gov; NCT07765433. Updated August 14, 2026. Accessed October 21, 2026. https://clinicaltrials.gov/study/NCT07765433
3. Akeso. Ivonescimab plus chemotherapy demonstrates significant overall survival benefit versus durvalumab plus chemotherapy in first-line biliary tract cancer: HARMONi-GI1 meets primary endpoint. Press release. Published August 25, 2026. Accessed October 21, 2026. https://www.akesobio.com/en/media/akeso-news/260826/
4. Oh DY, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022;1(8):EVIDoa2200015. doi:10.1056/EVIDoa2200015