izalontamab brengitecan (Bristol Myers Squibb)

Izalontamab brengitecan (BMS-986476) is an antibody-drug conjugate (ADC) targeting Nectin-4 (Poliovirus receptor-related protein 4), a cell-surface protein highly expressed in urothelial carcinoma and other solid tumors. Developed by Bristol Myers Squibb, the drug consists of a humanized monoclonal antibody conjugated to a camptothecin-derivative topoisomerase I inhibitor payload (brengitecan) via a cleavable linker. The mechanism of action involves the binding of the antibody to Nectin-4, followed by internalization of the ADC and subsequent release of the cytotoxic payload within the tumor cell. The released payload inhibits topoisomerase I, leading to DNA double-strand breaks and apoptosis. Izalontamab brengitecan is currently being evaluated in Phase 2/3 clinical trials, such as KRYSTAL-21, for the treatment of metastatic urothelial cancer in patients who have previously received immunotherapy, representing a potential new therapeutic option in the Nectin-4 targeted landscape.

Other names

Nectin-4 ADCNectin4 ADCNectin 4 ADCNectin-4-directed antibody-drug conjugateNectin4-directed antibody-drug conjugateNectin 4-directed antibody-drug conjugate