PD-(L)1×VEGF bispecific antibodies in solid tumors: clinical trial updates from ASCO 2026

PD-(L)1×VEGF bispecific antibodies integrate immune checkpoint blockade and VEGF inhibition within a single molecule, offering a potential strategy to overcome angiogenesis-associated immune resistance. At the 2026 ASCO Annual Meeting, the randomized phase 3 HARMONi-6 trial demonstrated an overall survival benefit with ivonescimab plus chemotherapy over tislelizumab plus chemotherapy in previously untreated advanced squamous non-small cell lung cancer (NSCLC), extending survival evidence to an active PD-1-based first-line comparator. Exploratory phase 2 studies of pumitamig, SSGJ-707, and HB0025 reported encouraging activity in first-line NSCLC, while phase 1 and 2 studies of IMM2510 and ivonescimab-based regimens suggested activity after prior immunotherapy. Smaller exploratory studies also reported activity in perioperative head and neck cancer, colorectal cancer, endometrial cancer, and mucosal melanoma. Collectively, these findings highlight the clinical potential of PD-(L)1×VEGF bispecific antibodies, with the strongest evidence in first-line squamous NSCLC and broader applications remaining hypothesis-generating. Future development should prioritize predictive biomarkers, resistance mechanisms, optimal treatment sequencing, and careful assessment of immune-related and VEGF-associated toxicities.