On July 9, 2021, enfortumab vedotin-ejfv, an antibody-drug conjugate targeting nectin-4, was granted regular approval. The agent is indicated for the treatment of adults with locally advanced or metastatic urothelial cancer who have received a PD-1 or PD-L1 inhibitor and platinum chemotherapy or are ineligible for cisplatin-containing chemotherapy and have received at least one prior line of therapy.1
Supporting Efficacy Data
Regular approval was based on findings from the confirmatory phase III EV-301 trial (ClinicalTrials.gov identifier NCT03474107) and a cohort of platinum-ineligible patients in the phase II EV-201 trial (NCT03219333).
In the EV-301 study, 608 patients were randomly assigned to receive enfortumab vedotin at 1.25 mg/kg on days 1, 8, and 15 of 28-day cycles (n = 301) or the investigator’s choice of single-agent chemotherapy (docetaxel, paclitaxel, vinflunine; n = 307). Median overall survival was 12.9 months in the enfortumab vedotin group vs 9.0 months in the chemotherapy group (hazard ratio [HR] = 0.70, 95% confidence interval [CI] = 0.56–0.89, P = .0014). Median progression-free survival was 5.6 months vs 3.7 months (HR = 0.62, 95% CI = 0.51–0.75, P < .0001). Objective response rates were 40.6% vs 17.9% (P < .0001).
Among 89 patients in the EV-201 study who had received a PD-1 or PD-L1 inhibitor, the confirmed objective response rate was 51% (95% CI = 39.8%–61.3%), including a complete response in 22%; the median duration of response was 13.8 months (95% CI = 6.4 months to not estimable).
How It Is Used
The recommended dose of enfortumab vedotin is 1.25 mg/kg (up to a maximum dose of 125 mg) via intravenous infusion over 30 minutes on days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Dose reductions are permitted for adverse reactions, and product labeling provides instructions on dose modification.
In the EV-301 trial, the most common adverse events of any grade in the enfortumab vedotin group were rash, fatigue, and peripheral neuropathy. Adverse events led to discontinuation of treatment in 17%, and fatal adverse events occurred in 3%.
Enfortumab vedotin has a new boxed warning for serious skin reactions and pneumonitis. The drug also has warnings/precautions for hyperglycemia, pneumonitis, peripheral neuropathy, ocular disorders, infusion-site extravasation, and embryofetal toxicity.
1. Padcev (enfortumab vedotin-ejfv) prescribing information, Astellas Pharma, July 2021. Available at www.accessdata.fda.gov. Accessed July 21, 2021.