UK Approves Tisotumab Vedotin for Recurrent Cervical Cancer, Demonstrating 30% Reduction in Death Risk
Key Insights
The UK's MHRA has approved tisotumab vedotin (Tivdak) for adults with recurrent or metastatic cervical cancer (search) that has progressed after prior systemic therapy.
Phase 3 trial data showed median overall survival of 11.5 months versus 9.5 months with chemotherapy, representing approximately 30% reduction in death risk.
The antibody-drug conjugate targets tissue factor (search) overexpressed in cervical tumors and demonstrated a 24% objective response rate in heavily pretreated patients.
The UK's Medicines and Healthcare products Regulatory Agency (MHRA) has approved tisotumab vedotin (Tivdak) for adults with recurrent or metastatic cervical cancer (search) whose disease has progressed after prior systemic therapy. The approval, granted on December 2, 2025, to Genmab AS (search) through the International Recognition Procedure, provides a new treatment option for a high-risk patient population with limited therapeutic alternatives.
Mechanism and Administration
Tisotumab vedotin is an antibody-drug conjugate that combines a tissue factor (search)-directed human monoclonal antibody with monomethyl auristatin E, a microtubule-disrupting agent. The therapy specifically targets tissue factor, which is overexpressed in several solid tumors, including recurrent cervical cancer (search). The treatment is administered as a 30-minute intravenous infusion once every three weeks.
Clinical Trial Evidence
The approval is supported by evidence from multiple clinical studies demonstrating significant efficacy in previously treated patients. In the phase 2 innovaTV 204 study, 102 patients were enrolled with 101 receiving at least one dose of tisotumab vedotin. The confirmed objective response rate reached 24%, including seven complete responses and 17 partial responses, demonstrating clinically meaningful activity in a heavily pretreated population.
The pivotal phase 3 innovaTV-301 trial provided the strongest evidence for approval, randomly assigning 502 patients to receive either tisotumab vedotin or investigator's-choice chemotherapy. Median overall survival was 11.5 months with tisotumab vedotin compared to 9.5 months in the chemotherapy arm, translating to roughly a 30% reduction in the risk of death. The confirmed objective response rate was also significantly higher with tisotumab vedotin at 17.8% versus 5.2% with standard treatment options.
Safety Profile
Ocular toxicity and peripheral neuropathy (search) emerged as the most notable adverse reactions in clinical trials. Common treatment-related events in the phase 2 study included alopecia (38%), epistaxis (30%), nausea, conjunctivitis (search) (26%), and fatigue (26%). Grade 3 or higher treatment-related adverse events occurred in approximately 28% of patients.
The most common side effects include eye problems such as conjunctivitis (search) and keratitis (search), and nerve problems such as numbness, tingling, or burning sensations in the hands and feet. Clinicians should remain alert to these conjunctivitis and keratitis symptoms as well as sensory neuropathic manifestations.
Regulatory Oversight
Julian Beach, Interim Executive Director of Healthcare Quality and Access at the MHRA, emphasized that "patient safety is our top priority" and confirmed that the agency "will continue to monitor its safety closely as it becomes more widely used." The Summary of Product Characteristics and Patient Information Leaflets will be published on the MHRA website within seven days of approval.
As with all licensed medicines, the MHRA will maintain close review of tisotumab vedotin's safety and effectiveness. Patients experiencing suspected side effects are encouraged to consult their healthcare providers and report directly to the MHRA Yellow Card scheme through the website or mobile app.