FDA Approves Tivdak for Advanced Cervical Cancer

The FDA has granted accelerated approval to Genmab/Seagen’s Tivdak (tisotumab vedotin-tftv), the first approved antibody-drug conjugate (ADC) for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Tivdak is approved under the FDA’s Accelerated Approval Program based on tumor response and the durability of the response. Approval is contingent upon confirmatory trials.

The approval is based on the phase 2 innovaTV 204 trial, which evaluated 101 patients. Results from the trial showed a 24% objective response rate, and the median duration of response was 8.3 months.

The most common adverse reactions were hemoglobin decreased (52%), fatigue (50%), lymphocytes decreased (42%), nausea (41%), peripheral neuropathy (39%), alopecia (39%), epistaxis (39%), conjunctival adverse reactions (37%), hemorrhage (32%), and leukocytes decreased (30%).

These data were featured in a late-breaking proffered paper oral presentation at ESMO 2020 and published in The Lancet Oncology in April 2021. A global, randomized phase 3 clinical trial (innovaTV 301) is under way and is intended to support global registrations.

Robert L. Coleman, M.D.

“Once recurrent or metastatic cervical cancer progresses, there is a need for more options for these patients,” Robert L. Coleman, M.D., chief scientific officer, US Oncology Research and lead investigator of the innovaTV 204 clinical trial, said in a statement. “This is an important development for patients with recurrent or metastatic cervical cancer.”

Tivdak is an ADC composed of Genmab’s human monoclonal antibody directed to tissue factor and Seagen’s ADC technology that uses a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E to the antibody. Nonclinical data suggests that the anticancer activity of the therapy is due to the binding of the ADC to tissue factor-expressing cancer cells.

In 2018, there were an estimated 293,394 women living with cervical cancer in the United States. The National Institutes of Health predicts there will be an additional 14,480 cases this year and an estimated 4,290 deaths from cervical cancer.