FDA Approves Tisotumab Vedotin in Recurrent or Metastatic Cervical Cancer

The FDA has granted accelerated approval to tisotumab vedotin (Tivdak) for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.¹

Tisotumab vedotin is the first and only approved antibody-drug conjugate for this indication.

“Once recurrent or metastatic cervical cancer progresses, there is a need for more options for these patients,” said Robert L. Coleman, MD, chief scientific officer, US Oncology Research and lead investigator of the innovaTV 204 clinical trial. “This is an important development for patients with recurrent or metastatic cervical cancer.

Accelerated approval for the antibody-drug conjugate was based on the findings of the phase 2 innovaTV 204 clinical trial (NCT03438396), updated data from which was published in The Lancet and previously presented during the European Society of Medical Oncology (ESMO) Virtual Congress 2020.²

Twenty-four percent of patients had an objective response rate (ORR) (95% CI, 15.9%-33.3%) that included 7% of patients experiencing a complete response and 17% with a partial response to tisotumab vedotin.³ Target lesions were reduced in 79% of patients after at least 1 post-baseline scan. Researchers also found that 49% of patients had stable disease and 24% had progressive disease after a median follow up of 10 months.

ORR was the primary end point of the study, but secondary end points included overall survival (OS), duration of response (DOR), time to response (TTR), progression-free survival (PFS), and safety. Median DOR was 8.3 months (95% CI, 4.2–not reached) with most responses considered rapid with a median TTR of 1.4 months (range, 1.1-5.1 months) and activity observed within the first 2 treatment cycles.

The 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). The study looked at 101 patients with an ECOG score of 0 or 1 who had received up to 2 prior systemic therapies. Patients enrolled on the trial had a median age of 50-years-old and 95% were white, 2% were Asian, 1% were Black, and 2% were classified as “other”. Fifty-eight percent of patients had an ECOG score of 0, 94% of patients had extrapelvic metastatic disease, and 68% had squamous cell carcinoma histology.

“Given the poor prognosis for this patient population and the low activity of current therapies in this setting, tisotumab vedotin, if approved, would represent a new treatment for women with recurrent or metastatic cervical cancer,” researchers had concluded prior to the approval of this drug.

Tisotumab vedotin also demonstrated a manageable and tolerable safety profile with the most common treatment-related adverse events (TRAEs) with a 10% or higher incidence rate was 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%) were also common TRAEs observed in patients. Most of these TRAEs 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.

“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” said Jan van de Winkel, PhD, chief executive officer, Genmab, in the press release. “The journey towards the approval of Tivdak started nearly two decades ago with innovative research by scientists at Genmab and Seagen and reflects on our purpose of making an impact in the lives of cancer patients and their families. Today’s announcement marks Genmab’s evolution into a fully integrated biotechnology company and we would like to thank patients, caregivers, investigators and our collaborators for their participation in our clinical studies.”

_References

_{1. Seagen and Genmab announce FDA accelerated approval for Tivdak™ (tisotumab vedotin-tftv) in previously treated recurrent or metastatic cervical cancer. News release. Seagen, Inc. September 20, 2021. Accessed September 20, 2021. https://bwnews.pr/3hSbILN}

_{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.}

_{3. Coleman RL, Lorusso D, Gennigens C, et al. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 May;22(5):609-619. doi: 10.1016/S1470-2045(21)00056-5}