Ivonescimab Tops Durvalumab Plus Chemotherapy in First-Line Biliary Tract Cancer
核心洞察
Akeso's Phase III HARMONi-GI1 trial met its primary overall survival endpoint with ivonescimab plus chemotherapy versus durvalumab plus chemotherapy in advanced biliary tract cancer (搜索).
The trial randomized 682 patients in China and is the first known Phase III study in advanced biliary tract cancer (搜索) to show OS superiority over anti-PD-(L)1 plus chemotherapy.
Full results will be presented as a Late-Breaking Abstract at the ESMO 2026 Presidential Symposium in Madrid on October 25 by Jian Zhou, MD.
Akeso's Phase III HARMONi-GI1 trial has produced a statistically significant and clinically meaningful overall survival (OS) advantage for ivonescimab plus chemotherapy over durvalumab plus chemotherapy in the first-line treatment of advanced biliary tract cancer (搜索) (BTC), according to topline results the company announced on August 25, 2026. The study also met the key secondary endpoints of progression-free survival (PFS) and objective response rate (ORR) at a pre-specified interim analysis.
The data will be presented as a Late-Breaking Abstract at the European Society for Medical Oncology 2026 Congress (ESMO 2026), held October 23 to 27 in Madrid, Spain. Jian Zhou, MD, of Shanghai, China, will deliver the results during Presidential Symposium II on Sunday, October 25, from 4:30pm to 6:15pm CET (11:30am to 1:15pm EDT). The presentation is listed as LBA8.
Trial Design and Comparator
HARMONi-GI1 is a single-region, multi-center, randomized, controlled, double-blinded Phase III study conducted in China and sponsored by Akeso, with all relevant data exclusively generated, managed, and analyzed by Akeso. The trial randomized 682 patients and evaluated ivonescimab plus chemotherapy against durvalumab plus chemotherapy as the comparator arm.
The comparator sets a meaningful bar. Durvalumab plus chemotherapy received FDA accelerated approval in September 2022 and became the established first-line standard in BTC after the TOPAZ-1 trial pushed median OS to 13 months, a roughly 1.6-month improvement over chemotherapy alone. HARMONi-GI1 pitted ivonescimab directly against that approved regimen rather than against chemotherapy alone.
Full numerical results remain under embargo until the ESMO session, so the magnitude of the OS difference between arms is not yet public. The immediate figure of interest when Zhou presents is the median OS difference between the two arms.
A Bispecific Built for Cooperative Binding
Ivonescimab, known as SMT112 in Summit Therapeutics' license territories (North America, South America, Europe, the Middle East, Africa, and Japan) and as AK112 outside those territories, is a potential first-in-class investigational bispecific antibody that combines PD-1 (搜索) blockade with VEGF (搜索)-blocking anti-angiogenesis effects in a single molecule. By design, it displays cooperative binding to each of its intended targets, with multifold higher affinity to PD-1 when VEGF is present.
Summit states that the molecule's engineered tetravalent structure, with four binding sites, is intended to enable higher avidity in the tumor microenvironment, where expression of both PD-1 (搜索) and VEGF (搜索) is potentially higher than in normal tissue. The design intent, together with a half-life of 6 to 7 days after the first dose and approximately 10 days at steady state, is to improve upon previously established efficacy thresholds, side effects, and safety profiles associated with prior approved drugs targeting these pathways. The structural and pharmacokinetic characterization was published by Zhong and colleagues in iScience in 2025.
Ivonescimab was engineered by Akeso and was initially approved for marketing authorization in China in May 2024. In China it is approved and commercially available for indications in non-small cell lung cancer (搜索) (NSCLC). It remains investigational and is not approved by any regulatory authority in Summit's license territories, including the United States and Europe.
A Broad Development Program
The BTC readout is the first Phase III ivonescimab result beyond NSCLC. Akeso is bringing nearly 30 studies to ESMO 2026, with ivonescimab featuring in 12 presentations. Those include rapid oral readouts in first-line favorable-risk renal cell carcinoma (搜索) (Phase Ib/II) and in recurrent or metastatic thymic carcinoma (搜索) from the iTHYM study. Cadonilimab, a PD-1 (搜索)/CTLA-4 (搜索) bispecific, appears in 15 presentations spanning gastric cancer (搜索), esophageal squamous cell carcinoma (搜索), colorectal cancer (搜索), and several rarer tumor types across neoadjuvant and advanced-disease settings.
There are currently 16 Phase III clinical studies of ivonescimab that are announced, ongoing, or completed: five Summit-sponsored global studies, one multiregional study sponsored by a cooperative group, and 10 conducted or being conducted in China by Akeso. Summit began clinical development in NSCLC, starting enrollment in 2023 in the multiregional Phase III HARMONi and HARMONi-3 trials, and began enrolling patients in HARMONi-7 in 2025. The company expanded into colorectal cancer (搜索) in the fourth quarter of 2025 with HARMONi-GI3 and announced initiation of HARMONi-GU1, a Phase II/III study in urothelial carcinoma (搜索), in 2026, with global site activations planned to begin by the fourth quarter of 2026.
Akeso is also conducting additional Phase III studies outside NSCLC and biliary tract cancer (搜索), including in triple-negative breast cancer, head and neck squamous cell carcinoma, small cell lung cancer, colorectal cancer (搜索), and pancreatic cancer. More than 5,000 patients have been treated with ivonescimab in clinical studies globally, and more than 100,000 when including those treated in a commercial setting in China, as noted by Akeso.
Regulatory Implications
A clinically meaningful OS gap beyond the roughly 1.6-month improvement durvalumab showed over chemotherapy alone in TOPAZ-1 would strengthen Akeso's case for regulatory filings outside China. The FDA accepted a BLA for ivonescimab in a different indication in January 2026.