FDA grants accelerated approval to enfortumab vedotin-ejfv for metastatic urothelial cancer

On December 18, 2019, the Food and Drug Administration granted accelerated approval to enfortumab vedotin-ejfv (PADCEV, Astellas Pharma US, Inc.) for adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting.

Enfortumab vedotin-ejfv is the first Nectin-4-directed antibody-drug conjugate to receive FDA approval.

Efficacy was investigated in EV-201 (NCT03219333), a single-arm, multicenter trial enrolling 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy. Patients received enfortumab vedotin-ejfv 1.25 mg/kg on days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity.

The main efficacy outcome measures were confirmed objective response rate (ORR) and response duration as assessed by blinded independent central review using RECIST 1.1. The ORR was 44% (95% CI: 35.1, 53.2) with complete and partial response rates of 12% and 32%, respectively. The estimated median response duration was 7.6 months (95% CI: 6.3, not estimable).

The most common adverse reactions (≥20%) included fatigue, peripheral neuropathy, decreased appetite, rash, alopecia, nausea, dysgeusia, diarrhea, dry eye, pruritus and dry skin. Diabetic ketoacidosis and death have occurred in patients treated with enfortumab vedotin-ejfv, regardless of pre-existing diabetes mellitus. Blood glucose levels should be monitored closely in patients with, or at risk, for diabetes mellitus or hyperglycemia.

The recommended enfortumab vedotin-ejfv dose is 1.25 mg/kg (up to a maximum dose of 125 mg) administered as an intravenous infusion over 30 minutes on days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.

View full prescribing information for PADCEV.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was approved approximately 3 months prior to the FDA goal date.

This indication is approved under accelerated approval based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. FDA granted this application priority review. Enfortumab vedotin-ejfv also was granted Breakthrough Therapy designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

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