Ivonescimab plus gemcitabine and cisplatin improved overall survival versus durvalumab plus chemotherapy in the Phase III HARMONi-GI1 trial.
Written By: Kalyani Boharapi,
M.Pharm (Reg. Affairs)
Reviewed By: Pharmacally Editorial Team
Akeso reported that the Phase III HARMONi-GI1 trial met its primary endpoint of overall survival (OS), with a prespecified interim analysis showing a statistically significant and clinically meaningful OS benefit for ivonescimab combined with gemcitabine and cisplatin (GemCis) compared with durvalumab plus GemCis in patients with previously untreated advanced biliary tract cancer (BTC).
The study also met its key secondary endpoints of progression-free survival (PFS) and objective response rate (ORR). Detailed efficacy and safety data are scheduled for presentation at the European Society for Medical Oncology (ESMO) 2026 Congress in Madrid on October 25.
HARMONi-GI1 is a randomized, controlled, double-blind, multicenter Phase III study conducted in China and sponsored by Akeso. All study data were generated, managed, and analyzed by Akeso.
Ivonescimab Combines PD-1 and VEGF Targeting
Ivonescimab is a bispecific antibody that simultaneously targets PD-1 and VEGF. Rather than administering separate immunotherapy and anti-angiogenic agents, the molecule combines both target activities within a single antibody.
Its engineered tetravalent structure provides four binding sites, while cooperative binding increases its affinity for PD-1 in the presence of VEGF. This molecular architecture is intended to enhance target engagement within the tumor microenvironment, where PD-1 and VEGF can be elevated relative to normal tissue.
Ivonescimab, also known as AK112 in Akeso’s territories and SMT112 in Summit Therapeutics’ licensed territories, has previously generated Phase III results in non-small cell lung cancer (NSCLC). HARMONi-GI1 extends its clinical development into gastrointestinal cancer.
Trial Tests Ivonescimab Against an Established Regimen
HARMONi-GI1 evaluated ivonescimab plus GemCis against durvalumab plus GemCis as first-line treatment for advanced BTC.
Durvalumab combined with gemcitabine and cisplatin has become an established first-line immunotherapy regimen for advanced biliary tract cancer. The HARMONi-GI1 design therefore compares the investigational regimen directly with a widely used immunotherapy-based treatment approach.
At the prespecified interim analysis, the ivonescimab regimen produced a statistically significant OS benefit and also met the key PFS and ORR endpoints. Akeso has not yet disclosed the numerical hazard ratio, median OS, median PFS, response rates, or detailed safety results. Those data are expected at the ESMO presentation and in a subsequent peer-reviewed publication.
ESMO Presentation Will Provide Detailed Findings
Jian Zhou, MD, will present the HARMONi-GI1 results during the ESMO 2026 Presidential Symposium II on October 25. The presentation is listed as LBA8.
Akeso described the result as its first positive Phase III study for ivonescimab in gastrointestinal cancer, following four positive Phase III results in lung cancer. The company is also evaluating the antibody in colorectal cancer, pancreatic cancer, triple-negative breast cancer, head and neck squamous cell carcinoma, and small cell lung cancer.
Regulatory Status and Next Steps
Ivonescimab received its first marketing authorization in China in May 2024 for a specific NSCLC population and has subsequently received additional approvals in China for other NSCLC settings. The drug remains investigational for biliary tract cancer and is not approved for this indication in the United States or Europe.
Summit is developing ivonescimab through multiple global Phase III programs, including studies in NSCLC, colorectal cancer, and urothelial carcinoma. The companies will need to establish the magnitude and durability of the HARMONi-GI1 survival benefit, together with its complete safety profile, through detailed clinical data and regulatory review.
The ESMO 2026 presentation is expected to provide the first comprehensive dataset from HARMONi-GI1 and clarify the clinical significance of ivonescimab plus GemCis in advanced biliary tract cancer.
Reference
HARMONi-GI1, a Phase III Trial Featuring Ivonescimab Plus Chemotherapy Compared to Durvalumab Plus Chemotherapy in First-Line Treatment of Patients with Advanced Biliary Tract Cancer from China, to Be Showcased in Presidential Symposium at ESMO 2026, Summit Therapeutics, 22 September 2026
Ivonescimab Plus Chemotherapy Demonstrates Significant Overall Survival Benefit Versus Durvalumab Plus Chemotherapy in First-Line Biliary Tract Cancer: HARMONi-GI1 Meets Primary Endpoint, Akeso, 25 August 2026
About the Writer
Kalyani Boharapi (LinkedIn) is a pharmacy professional and healthcare writer currently pursuing an M.Pharm in Regulatory Affairs at Dr. D. Y. Patil College of Pharmacy, with interests in pharmaceutical regulations, drug development, and healthcare innovation. She has academic exposure to dossier preparation, scientific writing, and regulatory documentation. Kalyani has also completed certification courses in Generative AI, AI in Pharma, and Bioinformatics, and actively participates in pharmaceutical conferences to stay updated with emerging trends and advancements in the healthcare and pharmaceutical industry.