October 2021: The FDA has given tisotumab vedotin-tftv (Tivdak, Seagen Inc.), a tissue factor-directed antibody and microtubule inhibitor combination, rapid approval for adult patients with recurrent or metastatic cervical cancer who are progressing on or after chemotherapy.
InnovaTV 204, an open-label, multicenter, single-arm clinical trial, was used to gain approval (NCT03438396). In 101 patients with recurrent or metastatic cervical cancer who had had no more than two prior systemic regimens in the recurrent or metastatic context, including at least one prior platinum-based chemotherapy treatment, efficacy was assessed. Sixty-nine percent of patients had previously received bevacizumab as part of a systemic treatment regimen. Tisotumab vedotin-tftv 2 mg/kg was given to patients every 3 weeks until disease progression or unacceptable toxicity.
The primary efficacy outcome measures were the confirmed objective response rate (ORR), as determined by an independent review committee (IRC) using RECIST v1.1, and response duration (DOR). With a median response time of 8.3 months, the ORR was 24 percent (95 percent CI: 15.9%, 33.3 percent) (95 percent CI: 4.2, not reached).
Hemoglobin 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 were the most common adverse reactions (25 percent), including laboratory abnormalities. A boxed warning for ocular toxicity is included on the product label.
The recommended dose is 2 mg/kg (up to 200 mg for patients under 100 kg) administered as a 30-minute intravenous infusion every three weeks until disease progression or intolerable toxicity.