Tisotumab Vedotin-tftv Received FDA Approval for Cervical Cancer

For adults treated with chemotherapy who have disease progression during or after treatment and recurrent or metastatic cervical cancer (cancer of the cervix), tisotumab vedotin-tftv (Tivdak, Seagen Inc.), a tissue factor-directed antibody and microtubule inhibitor conjugate, received accelerated approval on September 20, 2021 from the FDA (US Food and Drug Administration).

Traditional FDA Approval Following Accelerated Approval

On April 29, 2024, the FDA granted traditional approval to tisotumab vedotin-tftv (Tivdak, Seagen Inc., now part of Pfizer Inc.) for patients with recurrent or metastatic cervical cancer with disease progression after chemotherapy. Tisotumab vedotin-tftv had previously received accelerated approval for this indication.

Regular approval is based on innovaTV 301 (NCT04697628). This open-label, active-controlled, multicenter, randomized study enrolled 502 patients with cervical cancer who had received one or two previous systemic treatment regimens.

• Overall survival, the study's primary efficacy measure, was a median of 11.5 months in the tisotumab vedotin group (95% confidence interval: 9.8 - 14.9) and 9.5 months in the chemotherapy group (95% confidence interval: 7.9 - 10.7) (hazard ratio [HR]: 0.70, p-value: 0.0038).
• Median progression-free survival was 4.2 months in the tisotumab vedotin group (95% confidence interval: 4.0 - 4.4) and 2.9 months in the control group (95% confidence interval: 2.6 - 3.1) (HR: 0.67, p-value: <0.0001).
• The confirmed objective response rate was 17.8% in the tisotumab vedotin group (95% confidence interval: 13.3 - 23.1) and 5.2% in the control group (95% confidence interval: 2.8 - 8.8) (p-value: <0.0001).

The results fulfilled the postmarketing requirements following the earlier accelerated approval.

Initial FDA Approval Based on the innovaTV 204 Study

The approval was based on an open-label, multicenter, single-arm clinical trial called innovaTV 204. The 101 patients enrolled with recurrent or metastatic cervical cancer had previously received platinum-based chemotherapy but no more than 2 lines of treatment. 69% of patients had received bevacizumab as part of their previous systemic treatment. Patients received tisotumab vedotin-tftv at 2 mg/kg every 3 weeks until disease progression or unacceptable toxicity.

Results

The primary efficacy outcome measure planned in the study was objective response rate.

• With tisotumab vedotin-tftv, the objective response rate was 24% (95% confidence interval: 15.9% - 33.3%), and
• the median duration of response was 8.3 months(95% confidence interval: 4.2 - the upper confidence interval had not yet been reached).

The most common (≥25%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin, fatigue, decreased lymphocytes, nausea, peripheral neuropathy, alopecia, nosebleeds, conjunctival adverse reactions, bleeding, decreased leukocytes, increased creatinine, dry eye, prolonged bleeding time (increased PT), prolonged activated partial thromboplastin time (increased aPTT), diarrhea and rash. The product labeling includes a boxed warning for ocular toxicity.

The recommended dose is 2 mg/kg by intravenous infusion every 3 weeks, with the source's infusion timing phrase “every 30 minutes,” until disease progression or unacceptable toxicity (maximum 200 mg for patients weighing over 100 kg).

*