On 20 September 2021, the US Food and Drug Administration (FDA) granted accelerated approval to tisotumab vedotin-tftv (Tivdak, Seagen Inc.), a tissue factor-directed antibody and microtubule inhibitor conjugate, for adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.
Approval was based on innovaTV 204, an open-label, multicentre, single-arm clinical study. 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 3 weeks until disease progression or unacceptable toxicity.
The main efficacy outcome measures were confirmed objective response rate (ORR) as assessed by an independent review committee using RECIST v1.1 and duration of response.
The ORR was 24% (95% confidence interval [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 haemoglobin decreased, fatigue, lymphocytes decreased, nausea, peripheral neuropathy, alopecia, epistaxis, conjunctival adverse reactions, haemorrhage, leukocytes decreased, creatinine increased, dry eye, prothrombin international normalised ratio increased, activated partial thromboplastin time prolonged, diarrhoea, and rash. Product labelling includes a boxed warning for ocular toxicity.
The recommended dose is 2 mg/kg (up to a maximum of 200 mg for patients ≥100 kg) given as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity.
Full prescribing information for Tivdak is available here.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.