The FDA has granted accelerated approval to tisotumab vedotin-tftv (TivdakTM, Seagen) for patients with recurrent or metastatic cervical cancer who experience disease progression on or after chemotherapy.
"Few effective second-line treatments exist for women with recurrent or metastatic cervical cancer," wrote Robert Coleman, MD, Chief Scientific Officer of the US Oncology Network, and colleagues, in their publication of results of the phase 2 innovaTV/GOG-3023/ENGOT-cv6 trial, on which the approval was based. "Accordingly, we aimed to evaluate the efficacy and safety of tisotumab vedotin, a tissue factor–directed antibody-drug conjugate, in this patient population."
The single-arm trial evaluated 101 patients with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer who had disease progression on or after doublet chemotherapy with bevacizumab. Eligible patients had received one or two prior systemic regimens for recurrent/metastatic disease and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients received tisotumab vedotin 2.0 mg/kg intravenously once every three weeks until disease progression, unacceptable toxicity, or a maximum dose of 200 mg. The primary end point was confirmed objective response rate, assessed by an independent review committee.
At a median follow up of 10.0 months, tisotumab vedotin produced an objective response rate of 24%, with a complete response rate of 7%. The median duration of response was 8.3 months.
Adverse events and laboratory abnormalities occurring in at least 25% of patients included 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. The prescribing information for tisotumab vedotin includes a boxed warning for ocular toxicity.
"Tisotumab vedotin showed clinically meaningful and durable antitumor activity with a manageable and tolerable safety profile in women with previously treated recurrent or metastatic cervical cancer," concluded Dr. Coleman and colleagues in their April 2021 publication in Lancet Oncology. "Given the poor prognosis for this patient population and the low activity of current therapies in this setting, tisotumab vedotin [represents] a new treatment for women with recurrent or metastatic cervical cancer."
The recommended dose of tisotumab vedotin is 2 mg/kg administered intravenously over 30 minutes once every three weeks until disease progression or unacceptable toxicity, with a maximum dose of 200 mg for patients ≥100 kg.
For More Information
Coleman RL, Lorusso D, Gennigens C, et al (2021). Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol, 22(5):609-619. DOI:10.1016/S1470-2045(21)00056-5
TIVDAKTM (tisotumab vedotin-tftv) prescribing information. Seagen. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761208s000lbl.pdf
US Food & Drug Administration (2021). FDA grants accelerated approval to tisotumab vedotin-tftv for recurrent or metastatic cervical cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tisotumab-vedotin-tftv-recurrent-or-metastatic-cervical-cancer
Image credit: National Cancer Institute