The Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) seeking accelerated approval for tisotumab vedotin (Genmab and Seagen Inc) for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.
Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) targeted to tissue factor. It is composed of a fully human monoclonal antibody that binds to tissue factor and ADC technology that uses a protease-cleavable linker that covalently attaches monomethyl auristatin E (MMAE) to the antibody. Upon internalization, MMAE is released and induces cell death by microtubule disruption.
The BLA is supported by data from a multicenter, single-arm phase 2 trial (ClinicalTrials.gov: NCT03438396) that evaluated tisotumab vedotin as monotherapy in 101 adult females with recurrent or metastatic cervical cancer who were previously treated with doublet chemotherapy with or without bevacizumab. Patients received tisotumab vedotin intravenously once every 3 weeks until disease progression or toxicity. The primary endpoint was objective response rate (ORR), as assessed by RECIST v1.1.
Results showed a confirmed ORR of 24% (95% CI, 15.9-33.3) with a median duration of response (DOR) of 8.3 months. As for safety, the most common treatment-related adverse events (incidence of greater than or equal to 20%) included alopecia, epistaxis, nausea, conjunctivitis, fatigue and dry eye.
A Prescription Drug User Fee Act (PDUFA) target date of October 10, 2021 has been set for the application.
1. Genmab and Seagen announce U.S. FDA filing acceptance for Priority Review of tisotumab vedotin Biologics License Application for patients with recurrent or metastatic cervical cancer. [press release]. Copenhagen, Denmark and Bothell, WA: Genmab A/S and Seagen Inc.; April 9, 2021.
2. Genmab announces very favorable topline results from phase 2 clinical trial of tisotumab vedotin in recurrent or metastatic cervical cancer. [press release]. Copenhagen, Denmark: Genmab A/S; June 29, 2020.