FDA Has Granted Priority Review to Tisotumab Vedotin for Advanced Cervical Cancer


The FDA has accepted a biologics license application and granted it a priority review for tisotumab vedotin for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

Roger Dansey, MD

Roger Dansey, MD

The FDA has accepted a biologics license application (BLA) and granted it a priority review for tisotumab vedotin for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.1

A target action date of October 10, 2021, has been set by the FDA under the Prescription Drug User Fee Act.

“The FDA’s filing of the tisotumab vedotin BLA with Priority Review marks an important step forward for this ADC as a potential treatment for patients with recurrent or metastatic cervical cancer,” said Roger Dansey, MD, chief medical officer at Seagen, 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 antibody-drug conjugate directed at tissue factor, which is highly prevalent in cervical cancer, and covalently linked to the microtubule-disrupting agent MMAE via a protease-cleavable linker.

“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,” said Jan van de Winkel, PhD, chief executive officer of Genmab, in a statement.

Approval for tisotumab vedotin is based on findings from the pivotal phase 2 innovaTV 204 clinical trial (NCT03438396), data from which were presented during the European Society of Medical Oncology (ESMO) Virtual Congress 2020.2

The ongoing innovaTV 204 trial is a single-arm, global, multicenter study of tisotumab vedotin in patients with recurrent or cervical cancer who had progressed during or following doublet chemotherapy with bevacizumab (Avastin). A total of 101 patients were enrolled who had received up to 2 prior systemic regimens and had an ECOG performance of 0 or 1.

Objective response rate (ORR) by independent review committee per RECIST criteria was the primary end point and secondary end points included investigator-assessed ORR, overall survival (OS), duration of response (DOR), time to response (TTR), progression-free survival (PFS), and safety.

Patients had a median age of 50 years (range, 31-78). Ninety-five percent of patients were White, 2% were Asian, 1% were Black/African American, and 2% were classified as “other.” Fifty-eight percent of patients had an ECOG performance status of 0, 94% of patients had extrapelvic metastatic disease, and 68% had squamous cell carcinoma histology.

Fifty-four percent of patients had received prior cisplatin plus radiation therapy, 70% had received 1 previous line of systemic therapy for recurrent/metastatic disease. Sixty-three percent of patients had prior bevacizumab plus doublet chemotherapy as frontline therapy, and 56% of patients did not respond to their last systemic treatment.

The ORR was 24% (95% CI, 15.9%-33.3%) by independent review, which included a complete response rate of 7% and a partial response rate of 17%. Forty-nine percent of patients had stable disease and 24% had progressive disease. Target lesions were reduced in 79% of patients with at least 1 post-baseline scan.

The median DOR was 8.3 months (95% CI, 4.2–not reached). Most responses were rapid, with a median TTR of 1.4 months (range, 1.1-5.1), and activity was observed within the first 2 treatment cycles.

Median PFS was 4.2 months and median OS was 12.1 months. The 6-month PFS rate was 30% and the 6-month OS rate was 79%.

Tisotumab vedotin demonstrated a manageable and tolerable safety profile. The most common treatment-related adverse events (TRAEs) with a 10% or higher incidence rate 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 were grade 1/2, but grade 3/4 TRAEs occurred in 28% of patients. Of the 4 patients who died, 1 was due to septic shock that was considered to be treatment related.


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 9, 2021. https://bit.ly/3dKS5m8

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. Presented at: 2020 ESMO Virtual Congress; September 19-21, 2020; Virtual. Abstract LBA32.

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