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

The FDA has granted a priority review to the biologics license application (BLA) for tisotumab vedotin as a potential treatment for patients with recurrent or metastatic cervical cancer with progressive disease on, or following, chemotherapy.¹

The application is based on findings from the phase 2 innovaTV 204 trial (NCT03438396), where the antibody-drug conjugate (ADC) was found to elicit a 24% objective response rate (ORR) in patients with recurrent or metastatic cervical cancer who had prior doublet chemotherapy and bevacizumab (Avastin).²

The ORR was comprised of a 7% complete response rate, a 17% partial response rate, and a median duration of response (DOR) of 8.3 months (95% CI, 4.2–not reached). The median time to response (TTR) with the ADC was 1.4 months (range, 1.1-5.1) with activity reported within the first 2 cycles of treatment.

Under the Prescription Drug User Fee Act, the regulatory agency must make a decision on the application by October 10, 2021.

“The FDA’s filing of 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,” Roger Dansey, MD, chief medical officer at Seagen Inc., stated in a press release. “We are collaborating closely with the FDA throughout the review process to make this important therapy available to patients.”

The single-arm, multicenter, phase 2 trial enrolled a total of 101 previously treated patients with recurrent and/or metastatic cervical cancer. To be eligible for enrollment, patients had to have recurrent or extrapelvic metastatic disease and have experienced progressive disease during or after having received doublet chemotherapy with bevacizumab. They had to previously have received 2 or fewer systemic treatments and have an ECOG performance status of 0 to 1.

Study participants were given intravenous tisotumab vedotin at a dose of 2.0 mg/kg every 3 weeks until disease progression or unacceptable toxicity. The primary end point of the trial was ORR per RECIST v1.1 criteria and independent imaging review committee (IRC) assessment. Secondary end points of the trial included ORR per investigator assessment and RECIST v1.1 criteria, overall survival (OS), and safety.

Investigators also examined DOR, TTR, and progression-free survival (PFS) per IRC and investigator assessment. Biomarkers and health-related quality of life served as additional end points of interest.

The median age of study participants was 50 years, 95% were white, and 58% had an ECOG performance status of 0. Sixty-eight percent of patients had squamous cell carcinoma, 27% had adenocarcinoma, and 5% had adenosquamous carcinoma. Additionally, 94% of patients had extrapelvic metastatic disease at baseline.

Just over half, or 54%, of patients had prior cisplatin plus radiation treatment and 70% had previously received 1 line of systemic treatment for either recurrent or metastatic disease. Sixty-three percent of patients had prior bevacizumab and doublet chemotherapy as their first-line treatment and more than half of participants, or 56%, were not responsive to their last systemic treatment.

The median duration of treatment with tisotumab vedotin was 4.2 months and a median of 6 doses were given. A high dose intensity of 95.9% was noted with the agent. Four patients continued to receive treatment, while more than half (65%) discontinued due to radiographic progression. Of those who discontinued treatment, 13% did so because of adverse effects (AEs), 8% because of clinical progression, 5% because of withdrawn consent, 4% due to death, and 1% because of investigator decision.

Addition findings presented during the 2020 ESMO Virtual Congress indicated that 4% of the patients who received tisotumab vedotin had stable disease, while 24% had progressive disease per IRC assessment. The majority of patients, or 79%, reported a reduction in their target lesions.

With tisotumab vedotin, the median PFS was 4.2 months, and the OS was 12.1 months. The 6-month PFS rate was 30% and the 6-month OS rate was 79%.

The most commonly reported treatment-associated AEs comprised alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (24%), dry eye (23%), and myalgia (15%), among others. Most of the toxicities observed were just grade 1 or 2; however, 28% of participants experienced effects that were grade 3 or 4 in severity. Of the 4 patients who died, 1 died from septic shock that was determined to be associated with the ADC.

Toxicities of interest were ocular toxicity, bleeding, and peripheral neuropathy.

“We are pleased that tisotumab vedotin BLAS 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, added in the 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.”

References

1. Seagen and Genmab announce US FDA filing acceptance for priority review of tisotumab vedotin biologics license application for patients with recurrent or metastatic cervical cancer. News release. April 9, 2021. Accessed April 9, 2021. https://bit.ly/3s6I7AL
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):S1162-S1163. doi:10.1016/j.annonc.2020.08.2262