Summit Therapeutics Inc. announced it has entered into a clinical trial collaboration with GSK plc to evaluate ivonescimab, a novel, investigational PD-1 /VEGF bispecific antibody, in combination with risvutatug rezetecan (also known as GSK'227), GSK's novel investigational B7-H3 targeting antibody drug conjugate (ADC), across multiple solid tumor settings, including small cell lung cancer (SCLC). The intent of this agreement is to investigate the combination potential of ivonescimab and risvutatug reZetecan in multiple solid tumor environments to determine the safety profile and potential anti-tumor effects. Under the terms of the agreement, Summit will supply ivonescimab for the planned study, while GSK will manage the day-to-day clinical operations of the study.
Each party will maintain rights to their respective products, and the agreement is mutually non-exclusive. The study is expected to begin dosing patients in mid-2026. Risvutatug rezETecan, also known as GSK'227, is a novel investigational B7- H3-targeted antibody-drug conjugate compared of a fully human anti-B7-H3 monoclonal antibody covalently linked to a topoisomerase inhibitor payload.
GSK acquired exclusive worldwide rights (excluding China's mainland, Hong Kong, Macau, and Taiwan) from Hansoh Pharma to progress clinical development and commercialisation of risvutatug re zetecan. GSK's global phase III trial for risvutatug re Zetecan in relapsed ES-SCLC began in August 2025. Ivonescimab, known as SMT112 in Summit's license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 outside of Summit's license territories, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule.
By design, ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity to PD-1 when in the presence of VEGF. This is intended to differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. The company believe ivonescimab's specifically engineered tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al, SITC, 2023).
This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days after the first dose (Zhong, et Al, SITC, 20 23) increasing to approximately 10 days at steady state dosing, is to improve upon previously established efficacy thresholds, side-to-day dosing, and the study.
