Sigvotatug Vedotin (SGN-B6A): A Comprehensive Clinical and Scientific Review of an Investigational Integrin Beta-6-Targeted Antibody-Drug Conjugate

Executive Summary

Sigvotatug vedotin, also known as SGN-B6A, is an investigational, first-in-class antibody-drug conjugate (ADC) developed by Seagen (now a wholly owned subsidiary of Pfizer) that is currently in late-stage clinical development for the treatment of advanced solid tumors.[1] The agent is composed of a humanized monoclonal antibody specifically targeting integrin beta-6 (ITGB6), a cell surface receptor whose expression is highly restricted in healthy tissues but significantly upregulated in various carcinomas, where it correlates with increased invasiveness and poor prognosis.[3] The antibody is linked via a protease-cleavable linker to the potent microtubule-disrupting agent monomethyl auristatin E (MMAE), a clinically validated cytotoxic payload.[5]

The mechanism of action for sigvotatug vedotin is multifaceted. Its primary mechanism involves the targeted delivery of MMAE to ITGB6-expressing tumor cells, leading to internalization, payload release, cell cycle arrest, and apoptosis.[6] This targeted cytotoxicity is augmented by two critical secondary mechanisms: a "bystander effect," whereby the cell-permeable MMAE can kill adjacent, potentially ITGB6-negative tumor cells, and the induction of immunogenic cell death (ICD).[3] The latter mechanism provides a strong scientific rationale for combining sigvotatug vedotin with immune checkpoint inhibitors, as it effectively primes an anti-tumor immune response.