Tisotumab vedotin-tftv is approved by the FDA for recurrent or metastatic cervical cancer

April 2024: Tisotumab vedotin-tftv (Tivdak, Seagen Inc. [now a part of Pfizer Inc.]) has received formal approval from the Food and Drug Administration for the treatment of recurrent or metastatic cervical cancer that has worsened or spread following chemotherapy. Tisotumab vedotin-tftv had previously been granted expedited clearance for this specific indication.

The effectiveness of the treatment was assessed in the innovaTV 301 (NCT04697628) trial. This trial was open-label, active-controlled, multicenter, and randomized. It included 502 patients with recurrent or metastatic cervical cancer who had previously undergone one or two systemic treatment regimens.

These regimens involved chemotherapy with or without bevacizumab and/or an anti-PD-(L)-1 agent. People who had ongoing eye surface disease, cicatricial conjunctivitis or ocular Stevens-Johnson syndrome in the past, Grade ≥2 peripheral neuropathy, or clinically significant bleeding concerns or hazards were not included.

The patients were randomly assigned in a 1:1 ratio to receive either tisotumab vedotin at a dose of 2 mg/kg administered intravenously every 3 weeks, or the investigator’s choice of chemotherapy, which included topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed. Treatment was continued until either unacceptable toxicity occurred or there was disease progression.

The primary measure of effectiveness was overall survival (OS). The investigator evaluated the efficacy of the treatment by measuring progression free survival (PFS) and the confirmed objective response rate (ORR) using RECIST v1.1. The median overall survival (OS) was 11.5 months (95% confidence interval [CI]: 9.8, 14.9) in the tisotumab vedotin treatment group and 9.5 months (95% CI: 7.9, 10.7) in the chemotherapy group. The hazard ratio (HR) for OS was 0.70 (95% CI: 0.54, 0.89) with a p-value of 0.0038.

The median progression-free survival (PFS) was 4.2 months (95% confidence interval [CI]: 4.0, 4.4) in the group treated with tisotumab vedotin, and 2.9 months (95% CI: 2.6, 3.1) in the group treated with chemotherapy. The hazard ratio (HR) for PFS was 0.67 (95% CI: 0.54, 0.82), indicating a significant difference between the two treatment groups. The p-value was less than 0.0001.

The confirmed objective response rate (ORR) was 17.8% (95% confidence interval [CI]: 13.3, 23.1) and 5.2% (95% CI: 2.8, 8.8) in the respective treatment groups (p-value <0.0001). The results of this trial meet the post-marketing criteria of the earlier accelerated approval.

The most frequent side effects (≥25%), which also included abnormal laboratory results, were reduced hemoglobin levels, peripheral neuropathy, adverse responses in the conjunctiva, elevated aspartate aminotransferase levels, nausea, elevated alanine aminotransferase levels, exhaustion, reduced salt levels, nosebleeds, and constipation.

The suggested dosage for tisotumab vedotin is 2 mg/kg (with a maximum of 200 mg for individuals weighing ≥100 kg), given as an intravenous infusion lasting 30 minutes, every 3 weeks until there is disease progression or the patient experiences unacceptable toxicity.