On April 29, the U.S. Food and Drug Administration (FDA) granted traditional approval to tisotumab vedotin-tftv (Tivdak) for patients with recurrent or metastatic cervical cancer whose disease progressed on or after chemotherapy. Tisotumab vedotin-tftv previously received accelerated approval for this indication.
innovaTV 301
Efficacy was evaluated in innovaTV 301 (ClinicalTrials.gov identifier NCT04697628), an open-label, active-controlled, multicenter, randomized trial that enrolled 502 patients with recurrent or metastatic cervical cancer who had received one or two prior systemic regimens, including chemotherapy with or without bevacizumab and/or an anti–PD-1/-L1 agent. Patients were excluded if they had active ocular surface disease, any prior episode of cicatricial conjunctivitis or ocular Stevens-Johnson syndrome, grade ≥ 2 peripheral neuropathy, or clinically significant bleeding issues or risks.
Patients were randomly assigned 1:1 to receive either tisotumab vedotin at 2 mg/kg intravenously every 3 weeks or investigator’s choice of chemotherapy consisting of topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed, until unacceptable toxicity or disease progression.
The major efficacy outcome measure was overall survival. Additional efficacy outcome measures were progression-free survival and confirmed objective response rate as assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1. Median overall survival was 11.5 months (95% confidence interval [CI] = 9.8–14.9 months) in the tisotumab vedotin arm and 9.5 months (95% CI = 7.9–10.7 months) in the chemotherapy arm (hazard ratio [HR] = 0.70, 95% CI = 0.54–0.89, P = .0038). Median progression-free survival was 4.2 months (95% CI = 4.0–4.4 months) in the tisotumab vedotin arm and 2.9 months (95% CI = 2.6–3.1 months) for those treated with chemotherapy (HR = 0.67, 95% CI = 0.54–0.82, P < .0001). Confirmed objective response rate was 17.8% (95% CI = 13.3%–23.1%) and 5.2% (95% CI = 2.8%–8.8%) in the respective arms (P < .0001). This trial’s results fulfill the postmarketing requirement of the previous accelerated approval.
The most common adverse reactions (occurring in ≥ 25% of patients), including laboratory abnormalities, were decreased hemoglobin, peripheral neuropathy, conjunctival adverse reactions, increased aspartate aminotransferase, nausea, increased alanine aminotransferase, fatigue, decreased sodium, epistaxis, and constipation.
The recommended tisotumab vedotin dose is 2 mg/kg (maximum of 200 mg for patients ≥ 100 kg) administered 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. This application was granted Priority Review.
