BLA Submitted to FDA for Tisotumab Vedotin in Recurrent or Metastatic Cervical Cancer


A Biologics License Application was submitted to the FDA for tisotumab vedotin as treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

A Biologics License Application (BLA) was submitted to the FDA for tisotumab vedotin as treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, announced Seagen Inc. and Genmab A/S, in a press release.1

The BLA is supported by findings from the pivotal phase 2 innovaTV 204 clinical trial (NCT03438396), in which tisotumab vedotin achieved encouraging responses as monotherapy in patients with recurrent and/or metastatic cervical cancer who were previously treated with doublet chemotherapy and bevacizumab (Avastin).

“In the pivotal phase 2 study, tisotumab vedotin induced clinically meaningful and durable responses in this difficult to treat cervical cancer patient population, with a manageable and tolerable safety profile. Today’s submission marks an important milestone for tisotumab vedotin and a potential advance for patients with recurrent or metastatic cervical cancer for whom there is a high unmet need for effective new therapies,” said Roger Dansey, MD, chief medical officer, Seagen, Inc, in a statement. “We look forward to working with the FDA on the review of the application.”

According to results from the study presented during the European Society of Medical Oncology (ESMO) Virtual Congress 2020, treatment with tisotumab vedotin led to an objective response rate (ORR) of 24% (95% CI, 15.9%-33.3%), including complete responses in 7% and partial responses in 17%.2

The primary end point of the trial was ORR per RECIST v1.1 criteria. The secondary end points explored were investigator-assessed ORR per RECIST v1.1 criteria, overall survival (OS), safety, duration of response (DOR), time to relapse (TTR), and progression-free survival (PFS). The study also looked at exploratory end points including biomarkers and health-related quality of life.

Follow-up results from 10.0 months (range, 0.7-17.9) were presented during the 2020 ESMO Virtual Congress. It was reported that in the cohort of 101 patients, 49% of patients achieved stable disease and 24% of patients had progressive disease. The remaining 4% of patients were not evaluable for response. The disease control rate was 72% (95% CI, 62.5%-80.7%). Treatment with tisotumab vedotin also led to a 79% reduction in target lesions with 1 or more post-baseline scan.

The responses observed with the agent were regardless of histologic subtype. Responses appeared clinically meaningful in patients who had squamous disease (23%) and nonsquamous disease (25%). Moreover, responses were meaningful despite the number of prior therapies. Twenty-eight percent of patients who had 1 prior line of therapy responded to treatment, as did 13% of those who received 2 prior lines of therapy. Among those whose prior therapy was systemic, 26% responded. Finally, 19% of patients who received frontline doublet chemotherapy with bevacizumab responded to tisotumab vedotin monotherapy.

Investigators of the study also assessed how responses were impacted by membrane tissue factor (TF) expression, and responses were seen regardless of membrane TF expression.

In terms of survival, treatment with tisotumab vedotin achieved a median PFS of 4.2 months (95% CI, 3.2-4.6) and a median OS of 12.1 months (95% CI, 9.6-13.9). At 6 months, the PFS rate was 30% and the OS rate was 79%.

Tisotumab vedotin displayed a good safety profile overall in the study. No new safety signals were observed with the agent. The most common treatment-related AEs (TRAEs), which occurred in 10% of patients or more 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%). The majority of TRAEs were grade 1/2. In addition, 28% of patients experienced grade 3/4 TRAEs. Four patients died during the study, 1 of whom had septic shock that was considered to be treatment related.

There were a few AEs of interest noted during this study, which included ocular toxicity, bleeding, and peripheral neuropathy.

Patients enrolled to the innovaTV 204 received tisotumab vedotin at 2.0 mg/kg intravenously every 3 weeks until either disease progression or unacceptable toxicity. Tumor responses were assessed using CT/MRI at baseline every 6 weeks for the first 30 weeks, followed by every 12 weeks. The patients included were a median age of 50 years old (range, 31-78). Ninety-five percent of patients were White, 2% were Asian, 1% were Black, and 2% of patients were listed as other. Fifty-eight percent of patients had an ECOG performance status of 0, 68% of patients had squamous cell carcinoma, 27% had adenocarcinoma and 5% had adenosquamous carcinoma. Extrapelvic metastatic disease at baseline was observed in 94% of patients.

Patients were eligible to enroll if they had recurrent or extrapelvic metastatic disease, progressed during or following doublet chemotherapy with bevacizumab (if they were eligible), had received 2 or fewer prior systemic regimens, and had an ECOG performance status of 0 or 1.

“We believe, if approved, tisotumab vedotin as monotherapy has the potential to become an important treatment option 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.


1. Seagen and Genmab submit tisotumab vedotin biologics license application to the U.S. FDA for patients with recurrent or metastatic cervical cancer. News release. Seagen, Inc and Genmab A/S. February 11, 2021. Accessed February 11, 2021.

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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