On September 20, 2021, tisotumab vedotin-tftv, a tissue factor-directed antibody and microtubule inhibitor conjugate, was granted accelerated approval for the treatment of adults with recurrent or metastatic cervical cancer who have had disease progression on or after chemotherapy.1
Supporting Efficacy Data
Approval was based on findings from the multicenter innovaTV 204 trial (ClinicalTrials.gov identifier NCT03438396).1 In the trial, 101 patients 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, were treated with intravenous (IV) tisotumab vedotin at 2 mg/kg every 3 weeks until disease progression or unacceptable toxicity.
On independent review committee assessment, objective response was observed in 24 patients (24%, 95% confidence interval [CI] = 15.9%–33.3%), with a complete response in 7 patients (7%). The median duration of response was 8.3 months (95% CI = 4.2 months to not reached).
How It Is Used
The recommended dose of tisotumab vedotin is 2 mg/kg (up to a maximum of 200 mg for patients ≥ 100 kg) via IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Product labeling provides instructions on premedication and required eye care to reduce the risk of ocular adverse reactions. Instructions on dosage modification, including dose reduction, are provided for adverse reactions including keratitis, conjunctival ulceration, conjunctival or corneal scarring or symblepharon, conjunctivitis and other ocular adverse reactions, peripheral neuropathy, hemorrhage, and pneumonitis. Concomitant use with strong CYP3A4 inhibitors (eg, clarithromycin, erythromycin, diltiazem) requires close monitoring for tisotumab vedotin adverse reactions.
Among the 101 patients in the innovaTV 204 trial, the most common adverse events of any grade, including laboratory abnormalities, were decreased hemoglobin (52%), fatigue (50%), decreased lymphocytes (42%),nausea (41%), peripheral neuropathy (39%), alopecia (39%), epistaxis (39%), conjunctival adverse events (37%), hemorrhage (32%), decreased leukocytes (30%),dry eye (29%), increased creatinine (29%), increased prothrombin international normalized ratio (26%), prolonged activated partial thromboplastin time (26%), diarrhea (25%), and rash (25%). The most common grade 3 or 4 adverse events included fatigue (7%), peripheral neuropathy (7%), and hemorrhage (6%). The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (8%) and decreased hemoglobin (7%).
Serious adverse events occurred in 43% of patients, most commonly ileus (6%), hemorrhage (5%), pneumonia (4%), and peripheral neuropathy, sepsis, constipation, and pyrexia (3% each). Adverse events led to treatment discontinuation in 13%, most commonly due to peripheral neuropathy (5%) and corneal adverse events (4%). Fatal adverse events occurred in 4% of patients, including septic shock, pneumonitis, sudden death, and multisystem organ failure (1% each).
Tisotumabvedotin has a boxed warning for ocular toxicity and warnings/precautions for peripheral neuropathy, hemorrhage, pneumonitis, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving tisotumab vedotin.
1. Tivdak (tisotumab vedotin-tftv) for injection prescribing information, Seagen Inc and Genmab US, Inc, September 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761208s000lbl.pdf. Accessed October 4, 2021.