Ivonescimab lifts median survival to 14.9 months in biliary tract cancer
Key Facts
Akeso said the phase 3 HARMONi-GI1 trial met its primary endpoint, with ivonescimab plus chemotherapy showing improved overall survival compared with durvalumab plus chemotherapy in patients receiving first-line treatment for advanced biliary tract cancer. The result came in a prespecified interim analysis reviewed by an independent data monitoring committee. The trial also met its key secondary endpoints for progression-free survival and objective response rate. The company said the results represented, to its knowledge, the first phase 3 trial in this disease to show an overall survival benefit over a PD-(L)1 inhibitor combined with chemotherapy. This keeps the comparison tied to a regimen used as a standard of care, without implying that ivonescimab has received marketing approval.
Median overall survival was 14.9 months in the ivonescimab group, compared with 12.1 months in the durvalumab group. Akeso estimated the hazard ratio at 0.75, with a 95% confidence interval of 0.61 to 0.92 and a p-value of 0.0031. According to the company, the result corresponded to a 25% reduction in the risk of death at the interim analysis. The difference extended to survival rates at specified time points: the rate at 12 months was 59.7% versus 50.7%, and at 18 months it was 44.0% versus 32.5%. These rates add a time-based picture to the difference in median survival, with the rate remaining higher in the ivonescimab combination group at both reported time points.
Median progression-free survival was 8.4 months with ivonescimab, compared with 5.8 months with durvalumab. The hazard ratio for this measure was 0.61, with a 95% confidence interval of 0.51 to 0.72 and a p-value of less than 0.0001. The objective response rate was 53.8% in the ivonescimab group, compared with 32.5% in the comparison group, an absolute difference of 21.3 percentage points. Akeso said the p-value for the response difference was less than 0.0001. The disease control rate was also higher, at 91.5% versus 77.8%, with the ivonescimab group recording higher rates across the reported efficacy measures.
The analysis included 682 patients, with 340 assigned to ivonescimab plus chemotherapy and 342 to durvalumab plus chemotherapy. Median follow-up at the data cutoff was 14.3 months, according to Summit Therapeutics data. Akeso described durvalumab plus chemotherapy as the preferred first-line immunotherapy regimen, recommended in local and international guidelines and widely regarded as the standard of care. HARMONi-GI1 therefore compared the investigational treatment with a regimen described as standard therapy, rather than with a group receiving no immunotherapy. Akeso had announced on August 25, 2026, that the interim analysis had met the overall survival endpoint and key secondary endpoints, before later publishing details of the results presented by the company.
On safety, the rate of serious adverse events was similar between the groups, at 43.4% with ivonescimab and 43.7% with durvalumab. Bleeding of any grade was reported in 9.7% versus 6.5%, while grade 3 or higher bleeding occurred in 1.5% versus 1.8%. The rates therefore differed across the two reported bleeding measures, while the rate of serious adverse events remained similar. Akeso said the use of ivonescimab with chemotherapy as first-line treatment for biliary tract cancer had been proposed for priority review designation by China’s National Medical Products Administration; the proposal does not indicate that an approval decision has been issued. Summit also confirmed that ivonescimab remains investigational and unapproved in its licensed territories, including the United States and Europe.
The next step is to test the treatment in a U.S. registrational phase 2/3 study called EA2251, being developed by Summit in collaboration with the ECOG-ACRIN Cancer Research Group. The study will compare ivonescimab plus chemotherapy with chemotherapy regimens based on pembrolizumab or durvalumab in patients with advanced biliary tract cancer receiving first-line treatment. Summit announced the collaboration on October 21, 2026, and said activation of U.S. clinical trial sites is expected to begin in the fourth quarter of 2026. This offers an additional path to evaluate the results beyond the current trial. Akeso shares closed at 86.6 Hong Kong dollars on October 23, 2026, according to EL7 data.