Tisotumab Vedotin Receives FDA Priority Review in Recurrent Cervical Cancer

Tisotumab vedotin received accelerated approval from the FDA as a treatment for recurrent or metastatic cervical cancer following progression on chemotherapy in September 2021.

The FDA has granted priority review to a supplemental biologics license application (sBLA) seeking full approval for tisotumab vedotin-tftv (Tivdak) as a treatment for patients with recurrent or metastatic cervical cancer that has progressed following prior frontline therapy, according to a press release from Pfizer Inc.¹

The regulatory agency has set a Prescription Drug User Fee Act date of May 9, 2024 for the sBLA in this indication.

Tisotumab vedotin received accelerated approval from the FDA as a treatment for recurrent or metastatic cervical cancer following progression on chemotherapy in September 2021.² Supporting data for the accelerated approval came from the phase 2 innovaTV 204 trial (NCT03438396), in which the experimental agent elicited a confirmed overall response rate (ORR) of 24.0% (95% CI, 15.9%-33.3%) among those with previously treated disease.

Supporting data for the application intended to convert the agent’s accelerated approval to full approval came from the phase 3 innovaTV 301 trial (NCT04697628). According to findings presented at the 2023 Annual Global Meeting of the International Gynecologic Cancer Society (IGCS), tisotumab vedotin produced a median overall survival (OS) of 11.5 months (95% CI, 9.8-14.9) compared with 9.5 months (95% CI, 7.9-10.7) with chemotherapy (HR, 0.70; 95% CI, 0.54-0.89; P = .0038).³ Additionally, the OS rate at 12 months was 48.7% vs 35.3% in the experimental and control arms, respectively.

The median progression-free survival (PFS) in the tisotumab vedotin and chemotherapy arms, respectively, was 4.2 months (95% CI, 4.0-4.4) vs 2.9 months (95% CI, 2.6-3.1; HR, 0.67; 95% CI, 0.54-0.82; P <.0001). The 6-month PFS rate in each respective arm was 30.4% vs 18.9%. Additionally, investigators reported an ORR of 17.8% (95% CI, 13.3%-23.1%) compared with 5.2% (95% CI, 2.8%-8.8%) in each respective group.

The safety profile of tisotumab vedotin in the innovaTV 301 trial was comparable with prior reports of the agent.¹

“The phase 3 innovaTV 301 trial demonstrated a favorable benefit/risk profile, including improvement in [OS], and adds to the overall data supporting [tisotumab vedotin] as a treatment option for people with recurrent and metastatic cervical cancer who have limited treatment options,” Roger Dansey, MD, chief development officer of Oncology at Pfizer, said in the press release.¹ “The FDA acceptance of our sBLA for review is important progress toward continuing to offer an option that can extend the lives of more adults with cervical cancer.”

In the international, open-label phase 3 innovaTV 301 trial, 502 patients with recurrent or metastatic cervical cancer were randomly assigned 1:1 to receive tisotumab vedotin at 2.0 mg/kg intravenously every 3 weeks or (n = 253) or investigator’s choice of chemotherapy (n = 249). Patients in the chemotherapy arm were eligible to receive topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed.

The trial’s primary end point was OS. Secondary end points included PFS, ORR, time to response, duration of response, and safety. Those with metastatic or recurrent cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology as well as disease progression on or following prior chemotherapy with or without bevacizumab (Avastin) and an anti–PD-L1 agent were eligible for enrollment on the trial.

“Therapeutic options for metastatic cervical cancer that not only demonstrate a survival advantage but also include a novel approach to treating this condition are needed. This milestone underscores our commitment to continuing to deliver [tisotumab vedotin] as a treatment option to [patients] in the United States diagnosed with cervical cancer whose disease has progressed after first-line treatment,” Jan van de Winkel, PhD, chief executive officer at Genmab, concluded.¹

References

1. TIVDAK® supplemental biologics license application accepted for priority review by FDA for patients with recurrent or metastatic cervical cancer. News release. Pfizer Inc. January 9, 2024. Accessed January 9, 2024. https://rb.gy/8b2e8l
2. Seagen and Genmab announce FDA accelerated approval for TIVDAK™ (tisotumab vedotin-tftv) in previously treated recurrent or metastatic cervical cancer. News release. Seagen Inc. and Genmab A/S. September 20, 2021. Accessed January 9, 2024. https://bwnews.pr/2XJLowv
3. Slomovitz BM, Martin AG, Fujiwara K, et al. innovaTV 301/ENGOT-cx12/GOG-3057: a global, randomized, open-label, phase 3 study of tisotumab vedotin vs investigator's choice of chemotherapy in 2L or 3L recurrent or metastatic cervical cancer. Presented at 2023 Annual Global Meeting of the International Gynecologic Cancer Society; November 5-7, 2023; Seoul, Korea; abstract SE006/1616.