Tisotumab Vedotin-tftv Approved for Metastatic Cervical Cancer

Cervical cancer

The FDA has granted traditional approval to tisotumab vedotin-tftv (Tivdak®, Seagen Inc.) for recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. This indication was previously granted accelerated approval in 2021.  

Why it matters: “Tisotumab vedotin is an investigational antibody-drug conjugate composed of a tissue factor-directed human monoclonal antibody covalently linked to cytotoxic MMAE,” wrote Ignace Vergote, MD, Professor of Gynaecology-Oncology at UZ Leuven, Belgium, and colleagues, in their published results of the innovaTV 301 trial (NCT04697628), on which approval was based. “In the US, tisotumab vedotin monotherapy received accelerated approval for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Here, innovaTV 301 study results of tisotumab vedotin versus investigator’s choice of chemotherapy in patients with recurrent/metastatic cervical cancer following first-line therapy are presented.”

What they studied: Efficacy was measured in the phase 3, open-label, multicenter study of 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 randomized 1:1 to receive either 2 mg/kg of tisotumab vedotin intravenously every three weeks or investigator’s choice of chemotherapy—consisting of topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed—until unacceptable toxicity or disease progression.

Patients were not included in the study 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.

The primary efficacy end point measured was overall survival, with a secondary end point of progression-free survival and confirmed objective response rate, as per RECIST v1.1

What they found: The median overall survival was 11.5 months in those receiving tisotumab vedotin compared with 9.5 months in those receiving chemotherapy. Progression-free survival saw a median of 4.2 months in the tisotumab vedotin arm compared with 2.9 months in the chemotherapy arm. The confirmed objective response rate in those receiving tisotumab vedotin compared with chemotherapy was 17.8% and 5.2%, respectively.

Adverse events: The most common adverse events experienced by ≥25% of those receiving tisotumab vedotin, including laboratory abnormalities, were decreased hemoglobin, peripheral neuropathy, conjunctival adverse reactions, increased aspartate aminotransferase, nausea, increased alanine aminotransferase, fatigue, decreased sodium, epistaxis, and constipation.

Conclusion: “In the phase 3 innovaTV 301 study, tisotumab vedotin showed a statistically significant and clinically meaningful improvement in overall survival, progression-free survival, and objective response rate versus chemotherapy, with a manageable and tolerable safety profile in patients with second-line or third-line recurrent or metastatic cervical cancer,” concluded Dr. Vergote and colleagues.

Instructions: The recommended dosage is 2 mg/kg of tisotumab vedotin—with a maximum of 200 mg recommended for patients ≥100 kg—administered as an intravenous infusion over 30 minutes every three weeks, until disease progression or unacceptable toxicity.

For More Information

Vergote IB, Gonzalez Martin A, Fujiwara K, et al (2023). innovaTV 301/ENGOT-cx12/GOG-3057: A global, randomized, open-label, phase III study of tisotumab vedotin vs investigator’s choice of chemotherapy in 2L or 3L recurrent or metastatic cervical cancer. Ann Oncol, 34(suppl_2):S1276-S1277. DOI:10.1016/j.annonc.2023.10.029

Clinicaltrials.gov (2024). Tisotumab vedotin vs chemotherapy in recurrent or metastatic cervical cancer (innovaTV 301). NLM identifier: NCT04697628.

Tivdak® (tisotumab vedotin) prescribing information (2024). Seagen Inc. Available at: https://docs.seagen.com/Tivdak_Full_Ltr_Master.pdf

US Food and Drug Administration (2024). FDA approves tisotumab vedotin-tftv for recurrent or metastatic cervical cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tisotumab-vedotin-tftv-recurrent-or-metastatic-cervical-cancer

Image credit: ScienceAnimations.com. Licensed under CC BY-SA 4.0

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