The Food and Drug Administration granted traditional approval to tisotumab vedotin-tftv (Tivdak, Seagen Inc. [now a part of Pfizer Inc.]) for recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Tisotumab vedotin-tftv previously received accelerated approval for this indication.
Efficacy and Safety
Efficacy was evaluated in innovaTV 301 (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-(L)-1 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 randomized (1:1) to receive either tisotumab vedotin 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 (OS). Additional efficacy outcome measures were progression free survival (PFS) and confirmed objective response rate (ORR) as assessed by the investigator using RECIST v1.1. Median OS was 11.5 months (95% CI: 9.8, 14.9) in the tisotumab vedotin arm and 9.5 months (95% CI: 7.9, 10.7) in the chemotherapy arm (Hazard Ratio [HR] 0.70 [95% CI: 0.54, 0.89] p-value 0.0038). Median PFS was 4.2 months (95% CI: 4.0, 4.4) in the tisotumab vedotin arm and 2.9 months (95% CI: 2.6, 3.1) for those treated with chemotherapy (HR 0.67 [95% CI: 0.54, 0.82] p-value <0.0001). Confirmed ORR was 17.8% (95% CI: 13.3, 23.1) and 5.2% (95% CI: 2.8, 8.8) in the respective arms (p-value <0.0001). This trial’s results fulfill the post-marketing requirement of the previous accelerated approval.
The most common adverse reactions (≥25%), 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.
Expedited Programs
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
