On September 20, 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval to tisotumab vedotin-tftv (Tivdak™), a tissue factor-directed antibody and microtubule inhibitor conjugate, for adult patients with recurrent or metastatic cervical cancer whose disease has progressed on or after chemotherapy.
Approval was based on an open-label, multicenter, single-arm clinical trial (innovaTV 204; NCT03438396). Efficacy was evaluated in 101 patients with recurrent or metastatic cervical cancer who had received no more than two prior systemic regimens in the recurrent or metastatic setting, including at least one prior platinum-based chemotherapy regimen. Sixty-nine percent of patients had received bevacizumab as part of prior systemic therapy. Patients received tisotumab vedotin-tftv 2 mg/kg every three weeks until they experienced disease progression or unacceptable toxicity.
The main efficacy outcome measures were confirmed objective response rate (ORR) as assessed by an independent review committee using response evaluation criteria in solid tumors 1.1 and duration of response. The ORR was 24% (95% CI = 15.9%, 33.3%) with a median response duration of 8.3 months (95% CI = 4.2, not reached).
The most common adverse reactions (≥ 25%), including laboratory abnormalities, were decreased hemoglobin, fatigue, decreased lymphocytes, nausea, peripheral neuropathy, alopecia, epistaxis, conjunctival adverse reactions, hemorrhage, decreased leukocytes, increased creatinine, dry eye, increased prothrombin international normalized ratio, prolonged activated partial thromboplastin time, diarrhea, and rash. Product labeling included a boxed warning for ocular toxicity.
The recommended dose is 2 mg/kg, with up to a maximum of 200 mg for patients weighing at least 100 kg, given via IV infusion over 30 minutes every three weeks until patients develop disease progression or unacceptable toxicity.
The review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.
FDA granted the application was priority review. A description of FDA expedited programs is in the Guidance for IndustryꟷExpedited Programs for Serious ConditionsꟷDrugs and Biologics.
Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.