GSK5764227

GSK5764227 (ifinatamab deruxtecan) is an investigational B7-H3-directed antibody-drug conjugate (ADC) being co-developed by GSK and Daiichi Sankyo. It comprises a humanized anti-B7-H3 (CD276) monoclonal antibody conjugated to a topoisomerase I inhibitor payload, deruxtecan (a DXd derivative), via a tetrapeptide-based cleavable linker. B7-H3 is a member of the B7 family of immune checkpoint proteins and is frequently overexpressed in various solid malignancies, including small cell lung cancer (SCLC), while showing limited expression in normal tissues. Upon binding to B7-H3 on the surface of cancer cells, the ADC is internalized via endocytosis, and the payload is released by lysosomal enzymes. The released DXd then inhibits DNA topoisomerase I, leading to double-stranded DNA breaks and subsequent cell death. GSK5764227 is currently in Phase 3 development for the treatment of patients with relapsed small cell lung cancer.

Other names

ifinatamab deruxtecanI-DXd