Tisotumab Vedotin Earns European Approval for Pretreated Recurrent/Metastatic Cervical Cancer

Tisotumab Vedotin for Recurrent or

Metastatic Cervical Cancer

The European Commission has approved tisotumab vedotin (Tivdak) as monotherapy for the treatment of patients with previously treated recurrent or metastatic cervical cancer with disease progression on or after prior systemic therapy.1

The approval was supported by data from the phase 3 innovaTV 301 trial (NCT04697628), which evaluated the efficacy and safety of tisotumab vedotin vs investigator’s choice of chemotherapy in patients with advanced or recurrent cervical cancer who received prior chemotherapy. The trial met its primary end point with tisotumab vedotin demonstrating a 30% reduction in risk of death vs chemotherapy (HR, 0.70; 95% CI, 0.54-0.89, two-sided P = .0038). The median overall survival (OS) was 11.5 months (95% CI, 9.8-14.9) vs 9.5 months (95% CI, 7.9-10.7) with tisotumab vedotin vs chemotherapy, respectively.

“Recurrent or metastatic cervical cancer is a devastating disease, and patients can face a difficult treatment journey with limited options,” Ignace Vergote, MD, PhD, of University Hospitals Leuven, co-founder of European Network of Gynaecological Oncological Trial groups (ENGOT), and lead investigator on the innovaTV 301 clinical trial, stated in a news release. “In clinical trials, [tisotumab vedotin] demonstrated a superior OS benefit and [a] manageable safety profile compared [with] chemotherapy, supporting its position to become a potential new standard of care in this setting with a novel mechanism of action. This approval is an important step forward in the treatment landscape for advanced cervical cancer.”

The secondary end points of progression-free survival (PFS) and objective response rate (ORR), were also met. Treatment with tisotumab vedotin led to a 33% reduction in the risk of disease progression or death vs chemotherapy (HR, 0.67; 95% CI, 0.54-0.82; P < .0001).

Regarding safety, the most common adverse effects reported in at least 25% of patients treated with tisotumab vedotin included peripheral neuropathy (39%), nausea (37%), epistaxis (33%), conjunctivitis (32%), alopecia (31%), anemia (27%), and diarrhea (25%).

In April 2024, the FDA granted full approval to tisotumab vedotin-tftv for the treatment of patients with recurrent or metastatic cervical cancer who experienced disease progression on or after chemotherapy.2 The regulatory decision was also based on data from innovaTV 301.

The global, open-label, randomized study included patients with recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histologic features; measurable disease per RECIST 1.1 criteria and investigator assessment; and an ECOG performance status of 0 or 1.3 Patients were also required to have had disease progression during or after previous treatment with a standard-of-care systemic chemotherapy doublet, including paclitaxel plus cisplatin, carboplatin, or topotecan, along with bevacizumab (Avastin) and an anti-PD1 or –PD-L1 agent.

Enrolled patients were randomly assigned 1:1 to be treated with either tisotumab vedotin at 2.0 mg/kg once every 3 weeks or the investigator’s choice of chemotherapy, which comprised topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed.

Along with the primary end point of OS and key secondary end points of PFS and ORR, other secondary end points included time to response, duration of response, safety, and quality of life.

“We recognize the urgent need to accelerate science and innovate new treatment options for gynecologic cancers, including cervical cancer,” Brad Bailey, executive vice president and chief commercial officer of Genmab, added in the news release.1 “The European Commission approval of [tisotumab vedotin] marks a milestone in our work to transform the treatment paradigm and help improve outcomes for patients. As the first medicine that Genmab will bring to patients in Europe independently, we’re committed to bringing this important option to as many patients in Europe with previously treated recurrent or metastatic cervical cancer as possible.”

References

1. Tivdak (tisotumab vedotin) approved by European Commission for previously treated recurrent or metastatic cervical cancer. News release. Genmab. March 31, 2025. Accessed April 1, 2025. https://ir.genmab.com/news-releases/news-release-details/tivdakr-tisotumab-vedotin-approved-european-commission
2. FDA approves tivotumab vedotin-tftv for recurrent or metastatic cervical cancer. FDA. April 29, 2024. Accessed April 1, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tisotumab-vedotin-tftv-recurrent-or-metastatic-cervical-cancer
3. Vergote I, González-Martín A, Fujiwara K, et al. Tisotumab vedotin as second- or third-line therapy for recurrent cervical cancer. N Engl J Med. 2024;391(1):44-55. doi:10.1056/NEJMoa2313811