FDA Grants Priority Review to Tisotumab Vedotin for Recurrent/Metastatic Cervical Cancer


Based on results of the phase 2 innovaTV 204 trial, the FDA granted priority review to tisotumab vedotin as a potential therapy for patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

The FDA has accepted and granted priority review to a biologics license application (BLA) for tisotumab vedotin as therapy for patients with recurrent or metastatic cervical cancer whose disease progressed during or following chemotherapy treatment, according to Seagen Inc. and Genmab A/S who are responsible for developing the agent.1

The agency has set a target action date of October 10, 2021 for an approval decision under the Prescription Drug User Fee Act. The BLA was originally submitted in February of this year.

“The FDA’s filing of the tisotumab vedotin BLA with priority review marks an important step forward for this ADC [antibody-drug conjugate] as a potential treatment for patients with recurrent or metastatic cervical cancer,” Roger Dansey, MD, chief medical officer at Seagen, said in a press release. “We are collaborating closely with the FDA throughout the review process to make this important therapy available to patients.”

Tisotumab vedotin is an investigational ADC directed at tissue factor, which is known to be highly prevalent in cervical cancer and is linked with cancer pathophysiology and poor prognosis, and is covalently linked to the microtubule-disrupting agent MMAE via a protease-cleavable linker. Additionally, it is co-opted by tumor cells to promote tumor growth, angiogenesis, and metastasis.

The BLA submission was based on results of the phase 2 single-arm innovaTV 204 trial (NCT03438396) which is examining tisotumab vedotin monotherapy in patients with previously treated, recurrent, or metastatic cervical cancer. Results of the trial were previously presented at the European Society for Medical Oncology 2020 Virtual Congress.2

Results showed that tisotumab vedotin had the ability to induce an objective response rate (ORR) of 24% (95% CI, 15.9%-33.3%) in patients with recurrent and/or metastatic cervical cancer who were previously treated with doublet chemotherapy and bevacizumab (Avastin), which was comprised of complete responses in 7% of patients and partial responses in 17%. The median response duration was 8.3 months (95% CI, 4.2-not reached), with a median time to response of 1.4 months (range, 1.1-5.1).

The median progression-free survival in the patient cohort was 4.2 months and median overall survival was 12.1 months. Rates at 6 months were 30% and 79%, respectively. Of note, clinically meaningful responses were observed regardless of tumor histology, lines of prior therapy, responses to prior systemic treatment, and receipt of frontline doublet chemotherapy with bevacizumab.

Tisotumab vedotin had a manageable toxicity profile with no new safety signals identified. The most common treatment-related adverse events (TRAEs) with an incidence rate of 10% or higher included alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (24%), dry eye (23%), myalgia (15%), anemia (12%), asthenia (12%), arthralgia (12%), decreased appetite (11%), keratitis (11%), and pruritis (10%). Most of these events were grade 1/2 in severity with grade 3/4 TRAEs occurring in 28% of patients. Of the 4 patients who died, 1 was due to septic shock that was considered to be treatment related.

“We are pleased that the tisotumab vedotin BLA has been accepted with priority review by the FDA as there is an unmet need for effective therapies for women with recurrent or metastatic cervical cancer, who have disease progression on or after chemotherapy,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a press release. “This is an important milestone for Genmab as it brings us closer to our goal of bringing differentiated therapies to patients and transforming cancer treatment.”


1. Seagen and Genmab Announce U.S. FDA Filing Acceptance for Priority Review of Tisotumab Vedotin Biologics License Application for Patients with Recurrent or Metastatic Cervical Cancer. News release. Seagen Inc. and Genmab A/S. April 9, 2021. Accessed April 12, 2021. https://bit.ly/3mDRNRY

2. Coleman RL, Lorusso D, Gennigens C, et al. Tisotumab vedotin in previously treated recurrent or metastatic cervical cancer: results from the phase 2 innovaTV 204/GOG-3023/ENGOT-cx6 study. Ann Oncol. 2020;31(suppl 4):S1142-S1215. doi:10.1016/annonc/annonc325

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