FDA Approves Enfortumab Vedotin-ejfv for Previously Treated Advanced Urothelial Cancer

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On December 18, the U.S. Food and Drug Administration (FDA) granted accelerated approval to enfortumab vedotin-ejfv (Padcev) for adult patients with locally advanced or metastatic urothelial cancer who have previously received neoadjuvant or adjuvant treatment with a programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy in the locally advanced or metastatic setting.

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

“Antibody-drug conjugates are strategic tools in the targeted treatment of cancer. These conjugates combine the ability of monoclonal antibodies to target specific receptors on cancer cells and then deliver a drug to the cancer cell,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “[Enfortumab vedotin-ejfv] is an antibody-drug conjugate that targets Nectin-4, a cell surface protein expressed on bladder cancer cells and a cell-killing agent, monomethyl auristantin E.”

EV-201 Trial

Efficacy was investigated in EV-201, 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 at 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 version 1.1.


The ORR was 44% (95% confidence interval [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 (in ≥ 20% of patients) 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 preexisting 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.


The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.