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FDA Grants Accelerated Approval to Enfortumab Vedotin for the Treatment of Urothelial Cancers

Nichole Tucker
Published Online:12:30 AM, Thu December 19, 2019
Enfortumab vedotin-ejfv (Padcev) has been approved by the FDA for treatment of patients with locally advanced or metastatic urothelial cancers who had prior treatment with a PD-1 or PD-L1 inhibitor and a platinum-containing chemotherapy regimen, according to a press release from the FDA.1

The approval was based on results from a clinical trial (NCT03219333) of enfortumab vedotin monotherapy, which was administered to patients in this population. 

The overall response rate (ORR) observed in the study was 44%. Among these patients, 12% had a complete response to treatment and 32% had a partial response. These responses lasted for a median of 7.6 months.

In terms of safety and tolerability, the most common adverse events (AEs) observed from treatment with enfortumab vedotin were fatigue, peripheral neuropathy, decreased appetite, rash, alopecia, nausea, altered taste, diarrhea, dry eye, pruritis, and dry skin. Based on the AEs observed in this study, the FDA recommends patient monitoring for new or worsening peripheral neuropathy. They also recommend that physicians ensure venous access prior to beginning treatment with enfortumab vedotin and that patients who may be able to conceive use contraception while undergoing treatment in the study.

“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. “Padcev 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.”

Patients in the study were treated with intravenous enfortumab vedotin on days 1, 8, and 15, every 28 days. The primary end point of the study is ORR. The study is also evaluating co-secondary end points, which include duration of response, disease control rate, progression-free survival, and other safety and efficacy outcomes.

Patients were eligible to enroll if they had histological confirmation of urothelial cancer, metastatic disease, measurable disease, and an ECOG performance status of ≤1. Patients were required to have prior treatment with an immune checkpoint inhibitor and were stratified into 1 of 2 cohorts based on whether they had previously received platinum-based chemotherapy or not.

The study excluded individuals with ongoing sensory or motor neuropathy of grade 2 or higher; active central nervous system metastases; had immunotherapy for myocarditis, colitis, uveitis, or pneumonitis; uncontrolled tumor-related pain or spinal cord compression; or were previously enrolled to a study using enfortumab vedotin as treatment.

The study is actively recruiting patients and has a target completion date of May 2025.

The accelerated approval of enfortumab vedotin as a treatment in this patient population serves an unmet need. Further exploration of the drug in the clinical trial setting will be necessary for the clinical benefit of the drug to be verified.
FDA approves new type of therapy to treat advanced urothelial cancer. FDA website. https://bit.ly/35Bzdk7. Published December 18, 2019. Accessed December 18, 2019.

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