Tisotumab Vedotin Gains Full FDA Approval for Recurrent or Metastatic Cervical Cancer

FDA approval.| Image Credit: bakhtiarzein - stock.adobe.com

Tisotumab vedotin-tftv (Tivdak; Genmab A/S, Pfizer) was granted FDA approval to treat patients with recurrent or metastatic cervical cancer with a chance of disease progression on or after chemotherapy, the FDA announced.¹ The decision converts tisotumab vedotin's September 2021 accelerated approval to a full approval.²

The approval is supported by results from the phase 3 innovaTV 301 study (NCT04697628), an open label, multicenter, randomized control trial in which patients treated with tisotumab vedotin experienced improved overall survival (OS) compared with investigator's choice chemotherapy.^2,3 A total of 502 patients with recurrent or metastatic cervical cancer who had previously received 1 or 2 systemic regimens with or without bevacizumab and/or an anti-PD-1/PD-L1 agent were enrolled.³

Patients receiving tisotumab vedotin at 2 mg/kg intravenously every 3 weeks (n = 253) showed statistically significant and clinically meaningful improvements in median OS of 11.5 months compared with 9.5 months among patients on chemotherapy (HR, 0.70; 95% CI, 0.54-0.89; 2-sided P = .0038). Median progression-free survival was 4.2 months in the tisotumab vedotin arm compared with the 2.9 months in the chemotherapy arm.

“It is encouraging to see overall survival data among these patients and a manageable safety profile with tisotumab vedotin,” Brian Slomovitz, MD, director of gynecologic oncology and co-chair of the Cancer Research Committee at Mount Sinai Medical Center in Miami Beach, said in a statement.²

Recurrent and/or metastatic cervical cancer remains largely incurable, and the risk of recurrence following early diagnosis and initial treatment is around 61%, despite new technological advancements.

"Treatment options for patients with advanced or recurrent cervical cancer are limited," Slomovitz said. "...There is a high unmet need for more treatment options that have demonstrated survival benefit in the contemporary treatment landscape. The approval of tisotumab vedotin brings us a step closer to fulfilling that need.”

Tisotumab vedotin is an antibody-drug conjugate that applies a protease-cleavable linker that attaches the microtube-disrupting agent monomethyl auristatin E to the antibody. The microtube network is disrupted from actively dividing cells, leading them to cell cycle arrest, and apoptotic cell death. It is the first antibody-drug conjugate (ADC) with demonstrated OS data to receive full FDA approval in patients with recurrent or metastatic cervical cancer with a chance of disease progression on or after chemotherapy.²

The September 2021 accelerated FDA approval of tisotumab vedotin for adult patients with recurrent or metastatic cervical cancer with a disease progression on or after chemotherapy was based on confirmed objective response rates (24% [95% CI, 15.9%-33.3%]) and median duration of response (8.3 months [95% CI, 4.2, not reached]) in the single-arm, phase 2 innovaTV 204 trial.⁴

"Recurrent or metastatic cervical cancer is a particularly devastating and mostly incurable disease, and patients are in need of survival-extending treatment options,” Chris Boshoff, MD, PhD, chief oncology officer and executive vice president at Pfizer, said.² “Today’s full approval by the FDA reinforces the important role of TIVDAK for these patients, as the first antibody-drug conjugate with statistically significant prolonged overall survival data.”

Common adverse reactions among patients treated with tisotumab vedotin-tftv included laboratory abnormalities, decreased hemoglobin, peripheral neuropathy, conjunctival adverse reactions, increased aspartate aminotransferase, nausea, increased alanine aminotransferase, fatigue, decreased sodium, epistaxis, and constipation.¹

“This full approval opens up new treatment paths for this patient community who have long faced limited options," Tamika Felder, a cervical cancer patient advocate and founder and Chief Visionary Officer at Cervivor, Inc., commented.²

References

1. FDA approves tistumab vedotin-tftv for recurrent or metastatic cervical cancer. FDA. April 29, 2024. Accessed April 30, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tisotumab-vedotin-tftv-recurrent-or-metastatic-cervical-cancer

2. Tivdak (tisotumab vedotin-tftv) receives US FDA approval to treat recurrent or metastatic cervical cancer. Business Wire. April 29, 2024. Accessed April 30, 2024. https://www.businesswire.com/news/home/20240422914519/en/TIVDAK%C2%AE-tisotumab-vedotin-tftv-Receives-U.S.-FDA-Approval-to-Treat-Recurrent-or-Metastatic-Cervical-Cancer

3. Vergote I, Martín AG, Fujiwara K, et al. LBA9 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. Annals of Oncology. 2023;34:S1276-S1277. doi:10.1016/j.annonc.2023.10.029

4. FDA grants accelerated approval to tisotumab vedotin-tftv for recurrent or metastatic cervical cancer. News release. FDA. September 20, 2021. Accessed April 30, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tisotumab-vedotin-tftv-recurrent-or-metastatic-cervical-cancer