Drug Interactions between Mycobutin and telisotuzumab vedotin

Coadministration with potent inducers of CYP450 3A4 may decrease exposure to unconjugated monomethyl auristatin E (MMAE), the anti-mitotic and cytotoxic component of telisotuzumab vedotin. Telisotuzumab vedotin is an antibody-drug conjugate (ADC) that releases MMAE via proteolytic cleavage, and MMAE has been shown in vitro to be primarily metabolized by CYP450 3A4. Concomitant use of telisotuzumab vedotin with rifampin, a potent CYP450 3A4 inducer, is predicted to decrease unconjugated MMAE exposure (AUC) by 70% according to the product labeling. However, the clinical relevance is unknown, since the intact ADC containing the antibody component is required to bind to c-Met, the cell surface receptor for hepatocyte growth factor, which allows for internalization and cleavage by lysosomal proteases to enable intracellular delivery of MMAE.