IVONESCIMAB plus chemotherapy significantly improved survival compared with an alternative combination in patients with advanced biliary tract cancer, according to Phase III results presented at the European Society for Medical Oncology (ESMO) Congress 2026.
In the HARMONi-GI1 trial, median overall survival reached 14.9 months with ivonescimab, compared with 12.1 months with durvalumab. The combination also improved progression-free survival and objective response rates.
Biliary tract cancers, including cholangiocarcinoma and gallbladder cancer, are rare and advanced biliary tract cancer has a poor prognosis despite treatment.
Durvalumab plus chemotherapy is an established first-line treatment for advanced disease, but researchers sought to determine whether ivonescimab could improve on this approach.
Ivonescimab is a first-in-class bispecific antibody that targets both PD-1 and vascular endothelial growth factor (VEGF). It had previously shown encouraging activity alongside chemotherapy in a Phase II study in advanced biliary tract cancer.
The double-blind, randomised trial enrolled 682 patients in China with unresectable locally advanced or metastatic biliary tract cancer.
Patients were assigned to ivonescimab or durvalumab, each in combination with gemcitabine and cisplatin every 3 weeks for eight cycles. This was followed by maintenance treatment with the same antibody.
The ivonescimab group included 340 patients, while 342 were assigned to durvalumab.
Patients were stratified according to disease status and primary tumour location, including intrahepatic or extrahepatic cholangiocarcinoma and gallbladder cancer.
Overall survival was the primary endpoint of the trial. Progression-free survival and objective response rate were key secondary endpoints. The reported findings come from a preplanned interim analysis after a median follow-up of 14.3 months.
The study found that ivonescimab plus chemotherapy reduced the risk of death by 25% compared with durvalumab plus chemotherapy (HR: 0.75; 95% CI: 0.61–0.92; p=0.0031). The difference in median overall survival was 2.8 months.
Median progression-free survival was 8.4 months with ivonescimab versus 5.8 months with durvalumab. The abstract also reported a 39% reduction in the risk of disease progression or death with ivonescimab (HR: 0.61; 95% CI: 0.51–0.72; p<0.0001).
More patients also experienced an objective response with ivonescimab plus chemotherapy, at 53.8% versus 32.5% with durvalumab plus chemotherapy.
The investigators reported a manageable safety profile, with haematological toxicity among the most common treatment-emergent adverse events. No new safety signals were identified for ivonescimab.
The researchers concluded that the findings support ivonescimab plus chemotherapy as a potential new first-line standard of care.
Jian Shou, lead researcher, said the results of the trial are “potentially practice changing”, while promise of a possible new treatment option will “reinvigorate the field” of gastrointestinal (GI) cancers.
As the trial was conducted exclusively in China, where biliary tract cancer is more common, further research in more diverse populations may help establish how broadly the results apply, although researchers are confident the treatment will benefit diverse populations.
Reference
Zhou J et al. Ivonescimab plus chemotherapy versus durvalumab plus chemotherapy as first-line treatment for advanced biliary tract cancer: A randomized, controlled, double-blinded, phase 3 trial (HARMONi-GI1). Abstract LBA8. ESMO Congress 2026. Clinical trial: NCT06591520. ESMO Congress, 23-27 October 2026.
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