trastuzumab vedotin

Trastuzumab vedotin is an investigational antibody-drug conjugate (ADC) that combines the humanized anti-HER2 monoclonal antibody, trastuzumab, with the potent microtubule-disrupting agent monomethyl auristatin E (MMAE). The cytotoxic payload is attached to the antibody via a protease-cleavable valine-citrulline (vc) linker, a combination collectively referred to as 'vedotin'. The drug's mechanism of action involves the selective binding of trastuzumab to the human epidermal growth factor receptor 2 (HER2) on the surface of cancer cells, followed by internalization of the ADC-receptor complex. Once inside the lysosome, the linker is cleaved by proteases, releasing MMAE into the cytoplasm where it inhibits tubulin polymerization, leading to G2/M phase cell cycle arrest and apoptosis. While other HER2-targeted ADCs like trastuzumab emtansine and trastuzumab deruxtecan are clinically approved, trastuzumab vedotin (specifically the candidate PF-06804105) has been evaluated in early-phase clinical trials for HER2-positive solid tumors and is frequently used in research to study the off-target hematological toxicities, such as neutropenia, associated with MMAE-based conjugates.

Other names

trastuzumab monomethyl auristatin Etrastuzumab-mc-vc-PAB-MMAE