Tissue factor-targeted antibody-drug conjugates in cervical cancer: Focus on tisotumab vedotin.

Abstract

Cervical cancer remains a major global health burden, and treatment options after progression of recurrent or metastatic disease remain limited. Tisotumab vedotin (TV) is a tissue factor-directed antibody-drug conjugate that delivers monomethyl auristatin E after target binding and internalization. In innovaTV 204, TV achieved an objective response rate of 24.0% and a median duration of response of 8.4 months; innovaTV 301 subsequently demonstrated superior overall survival, progression-free survival, and response rate versus investigator's choice chemotherapy. In this review I examine the biological rationale for the use of TV, the design of TV and its clinical use, the clinical evidence for its use, as well as how toxicity is managed with treatment with TV, and I discuss unresolved issues surrounding TV, specifically as they pertain to the very limited clinical data that have been published regarding resistance mechanisms for the TV treatment modality. I also discuss the important need for the development of predictive biomarkers for TV and the development of rational combinations with other agents for use in combination with TV.