EMA Validates Tisotumab Vedotin Marketing Application in Cervical Cancer

The European Medicines Agency (EMA) has validated a marketing authorization application (MAA) for tisotumab vedotin-tftv (Tivdak) as a therapy for patients with metastatic or recurrent cervical cancer that has progressed during or following prior systemic therapy, according to a press release from Genmab and Pfizer.¹

If the EMA grants approval to tisotumab vedotin, the agent would become the first antibody drug conjugate to receive marketing authorization in the European Union as a treatment for those with cervical cancer.

“The validation of our application is an important milestone supporting our commitment to bringing a new therapeutic option for recurring or metastatic cervical cancer to more patients,” Jan van de Winkel, PhD, chief executive officer at Genmab, said in the press release. “There continues to be a need for therapeutic options for these patients, and we’re dedicated to delivering potentially improved outcomes to women diagnosed with this devastating disease.”

Supporting data for the application came from the phase 3 innovaTV 301 trial (NCT04697628) assessing tisotumab vedotin compared with chemotherapy among those with previously treated recurrent or metastatic cervical cancer. The single-arm phase 2 innovaTV 204 trial (NCT03438396) evaluated tisotumab vedotin monotherapy for patients in the aforementioned population.

According to data from the innovaTV 301 trial presented at the 2023 Annual Global Meeting of the International Gynecologic Cancer Society (IGCS), the median overall survival (OS) was 11.5 months (95% CI, 9.8-14.9) with tisotumab vedotin vs 9.5 months (95% CI, 7.9-10.7) with chemotherapy (HR, 0.70; 95% CI, 0.54-0.89; P = .0038).² The 12-month OS rate in each respective arm was 48.7% vs 35.3%. Additionally, the overall response rate (ORR) was 17.8% (95% CI, 13.3%-23.1%) vs 5.2% (95% CI, 2.8%-8.8%) in each respective arm, and the disease control rate (DCR) was 75.9% (95% CI, 70.1%-81.0%) vs 58.2% (95% CI, 51.8%-64.4%).

Adverse effects (AEs) of special interest in the innovaTV 301 trial appeared to be comparable with prior reports of tisotumab vedotin. Any-grade treatment-related AEs (TRAEs) affected 87.6% of patients who received tisotumab vedotin compared with 85.4% of those who were treated with chemotherapy, with the most common any-grade toxicities in each arm including anemia (12.8% vs 43.9%) and neutropenia (6.4% vs 21.8%).

In the innovaTV 301 trial, 502 patients were randomly assigned 1:1 to receive tisotumab vedotin at 2.0 mg/kg intravenously every 3 weeks (n = 253) or chemotherapy (n = 249). Those 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 progression-free survival, ORR, and safety.

The FDA granted priority review to a supplemental biologics license application (sBLA) for tisotumab vedotin as a treatment for those with recurrent or metastatic cervical cancer in January 2024.³ The regulatory agency set a Prescription Drug User Fee Act date of May 9, 2024 for tisotumab vedotin in this indication.

The sBLA is intended to convert the FDA’s accelerated approval of tisotumab vedotin in cervical cancer in September 2021 to full approval status.⁴ Supporting data for the application came from the phase 3 innovaTV 301 trial.

“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. 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,” Roger Dansey, MD, chief development officer of Oncology at Pfizer, said in a press release at the time the FDA granted priority review to tisotumab vedotin.³

References

1. Tisotumab vedotin marketing authorization application validated by European Medicines Agency for treatment of recurrent or metastatic cervical cancer.News release. February 2, 2024. Accessed February 5, 2024. http://tinyurl.com/4djy9fmw
2. 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.
3. 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 February 5, 2024. https://rb.gy/8b2e8l
4. 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 February 5, 2024. https://bwnews.pr/2XJLowv