Bridgewater Weighs Potential Sequencing After Ivonescimab and the Future of BTC Therapy

The PD-1/VEGF bispecific antibody ivonescimab plus chemotherapy improved overall survival (OS) vs durvalumab (Imfinzi) plus chemotherapy as first-line treatment for advanced biliary tract cancer (BTC), according to data presented from the phase 3 HARMONi-GI1 trial (NCT06591520) presented at the 2026 European Society for Medical Oncology (ESMO) Congress.

Patients who received ivonescimab had a median of 14.9 months’ overall survival (OS) vs 12.1 months (HR, 0.75; 95% CI, 0.61-0.92; P = .0031) with durvalumab (Imfinzi) plus chemotherapy. The median progression-free survival was 8.4 vs 5.8 months (HR, 0.61; 95% CI, 0.51-0.72; P < .0001), respectively. The respective objective response rates were 53.8% vs 32.5% (P < .0001).

John Bridgewater, BA, MBBS, MRCP, PhD, professor at University College London, said in an interview that a positive result would make ivonescimab plus chemotherapy a candidate for a new first-line standard of care, noting that it is the first of several similar agents entering the space, with others beginning first-line studies.

When asked how sequencing targeted therapies would be shaped by this development, he brings up how the academic SAFIR-ABC10 umbrella study (NCT05615818), nearing completion, could move targeted therapy to maintenance at the 12-week point. First-line trials are also evaluating trastuzumab deruxtecan (Enhertu) and zanidatamab (Ziihera) in HER2-positive disease and ivosidenib (Tibsovo) in IDH1-mutated disease. According to Bridgewater, targeted therapies have extended survival from about 1 year to 2 to 4 years and have rendered some patients operable. Immunotherapy, by contrast, lacks a biomarker to select patients.

When asked how he sees therapy evolving over the next 5 years, Bridgewater stresses that targeted therapies have raised median OS by several years in the appropriate patient populations, and patients should never miss the opportunity to receive targeted therapy. Immunotherapy’s benefit so far has been modest in addition to chemotherapy, and is not as personalized. Even as bispecifics and antibody-drug conjugates improve upon chemoimmunotherapy, actionable biomarker targets remain crucial to getting the best outcomes.

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). Presented at ESMO Congress. October 23-27, 2026; Madrid, Spain. LBA8.