On April 29, 2024, tisotumab vedotin-tftv (Tivdak) was granted regular approval for recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.¹ Tisotumab vedotin is a tissue factor–directed antibody and microtubule inhibitor conjugate.

The agent was granted accelerated approval for this indication in September 2021.

Supporting Efficacy Data

Approval was based on findings in the open-label innovaTV 301 trial (ClinicalTrials.gov identifier NCT04697628), in which 502 patients were randomly assigned to tisotumab vedotin at 2 mg/kg every 3 weeks (n = 253) or investigator’s choice of chemotherapy (n = 249; topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) until disease progression or unacceptable toxicity. Patients had received one to two prior systemic regimens, including chemotherapy with or without bevacizumab and/or anti–PD-L1 therapy. Patients were excluded if they had active ocular surface disease, any prior episode of cicatricial conjunctivitis or ocular Stevens-Johnson syndrome, grade ≥ 2 peripheral neuropathy, or clinically significant bleeding issues or risks.

Median overall survival was 11.5 months (95% confidence interval [CI] = 9.8–14.9 months) in the tisotumab vedotin group vs 9.5 months (95% CI = 7.9–10.7 months) in the chemotherapy group (hazard ratio [HR] = 0.70, 95% CI = 0.54–0.89, P = .0038). Median progression-free survival was 4.2 months vs 2.9 months (HR = 0.67, 95% CI = 0.54–0.82, P <. 0001).

How It Is Used

The recommended tisotumab vedotin dose is 2 mg/kg (maximum of 200 mg for patients ≥ 100 kg) via intravenous infusion every 3 weeks until disease progression or unacceptable toxicity.

Product labeling provides instructions on premedication and required eye care to reduce risk of ocular adverse reactions. Labeling provides instructions on dosage modification, including dose reduction, for adverse reactions including keratitis, conjunctival and other ocular adverse reactions, peripheral neuropathy, hemorrhage, pneumonitis, and severe cutaneous reactions. Information is provided on concomitant use with strong CYP3A4 inhibitors (eg, clarithromycin, erythromycin, diltiazem). Use should be avoided in patients with moderate or severe hepatic impairment.

Safety Profile

In the innovaTV 301 trial, the most common adverse events of any grade in the tisotumab vedotin group were peripheral neuropathy (38%), conjunctival adverse events (37%), nausea (33%), fatigue (28%), epistaxis (26%), constipation (25%) alopecia (24%), decreased appetite (24%), diarrhea (22%), hemorrhage (21%), corneal adverse events (21%), and dry eye (21%); the most common in the chemotherapy group were nausea (40%), fatigue (32%), and pyrexia (21%). The most common grade 3 or 4 adverse events in the tisotumab vedotin group included peripheral neuropathy (6%), fatigue (6%), and urinary tract infection (5%). The most common grade 3 or 4 laboratory abnormalities were decreased hemoglobin (7%) and neutrophils (3%) and increased alanine aminotransferase (3%).

Serious adverse events occurred in 33% of the tisotumab vedotin group, most commonly urinary tract infection (4.8%), small intestinal obstruction (2.4%), sepsis (2%), abdominal pain (2%), and hemorrhage (2%). Adverse events led to discontinuation of treatment in 15%, most commonly peripheral neuropathy (6%) and ocular adverse events (6%). Adverse events led to death in 1.6% of patients, including acute kidney injury, pneumonia, sepsis, and Stevens-Johnson syndrome.

Tisotumab vedotin has a boxed warning for ocular toxicity. It has warnings/precautions for peripheral neuropathy, hemorrhage, pneumonitis, severe cutaneous reactions (including Stevens-Johnson syndrome), and embryofetal toxicity. Patients should be advised not to breastfeed while receiving tisotumab vedotin.

REFERENCE

1. Tisotumab vedotin-tftv (Tivdak) for injection, for intravenous use, prescribing information, Seagen Inc and Genmab US, Inc, April 2024. Available at https://www.tivdakhcp.com. Accessed May 31, 2024.