On April 29, 2024, the U.S. Food and Drug Administration (FDA) granted traditional approval to tisotumab vedotin-tftv (Tivdak®) for recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Tisotumab vedotin-tftv previously received accelerated approval for the indication.

FDA update

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 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 or higher peripheral neuropathy, or clinically significant bleeding issues or risks.

Patients were randomized 1:1 to receive either tisotumab vedotin 2 mg/kg via IV every three weeks or investigator’s choice of chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed), until they experienced 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 (HR = 0.70 [95% CI = 0.54, 0.89]; p = 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 < 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 < 0.0001). FDA said that the results fulfill the post-marketing requirement of its previous accelerated approval.

The most common adverse reactions reported in at least 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 weighing 100 kg or higher) administered as an IV infusion over 30 minutes every three weeks until patients experience disease progression or unacceptable toxicity.

View the full prescribing information for tisotumab vedotin.

FDA’s review used the Assessment Aid, a voluntary submission from the applicant to facilitate the assessment. The 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 800-FDA-1088.

For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact the Oncology Center of Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.