On September 20, the U.S. Food and Drug Administration (FDA) granted accelerated approval to tisotumab vedotin-tftv (Tivdak), a tissue factor–directed antibody and microtubule inhibitor conjugate, for adult patients with recurrent or metastatic cervical cancer who experienced disease progression on or after chemotherapy.
Approval was based on innovaTV 204, an open-label, multicenter, single-arm clinical trial (ClinicalTrials.gov identifier: NCT03438396). Efficacy was evaluated in 101 patients with recurrent or metastatic cervical cancer who had received no more than two prior systemic regimens in the recurrent or metastatic setting, including at least one prior platinum-based chemotherapy regimen. Sixty-nine percent of patients had received bevacizumab as part of prior systemic therapy. Patients received tisotumab vedotin at 2 mg/kg every 3 weeks until disease progression or unacceptable toxicity.
The main efficacy outcome measures were confirmed objective response rate as assessed by an independent review committee using Response Evaluation Criteria in Solid Tumors version 1.1, and duration of response. The objective response rate was 24% (95% confidence interval [CI] = 15.9%–33.3%) with a median response duration of 8.3 months (95% CI = 4.2 months–not reached).
The most common adverse reactions (≥ 25%), including laboratory abnormalities, were decreased hemoglobin, fatigue, decreased lymphocytes, nausea, peripheral neuropathy, alopecia, epistaxis, conjunctival adverse reactions, hemorrhage, decreased leukocytes, increased creatinine, dry eye, increased prothrombin international normalized ratio, prlonged activated partial thromboplastin time, diarrhea, and rash. Product labeling includes a boxed warning for ocular toxicity.
The recommended dose of tisotumab vedotin is 2 mg/kg (up to a maximum of 200 mg for patients ≥ 100 kg) given as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment, and this application was granted Priority Review.