Overview
Tisotumab vedotin is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed against cell surface tissue factor (TF) and Seagen’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggests that the anticancer activity of tisotumab vedotin is due to the binding of the ADC to TF expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death of actively dividing cells. In vitro, tisotumab vedotin also mediates antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC).
In 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval for tisotumab vedotin for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. In April 2024, FDA approved the supplemental Biologics License Application (sBLA) granting full approval for tisotumab vedotin (or TIVDAK®) for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.
In September 2022, Zai Lab obtained an exclusive license to develop and commercialize tisotumab vedotin in mainland China, Hong Kong, Macau, and Taiwan from Seagen.