FDA Offers Priority Review to Enfortumab Vedotin-Ejfv, Pembrolizumab Combination for Metastatic Bladder Cancer


If approved, this combination will become a first-line treatment option for patients who are cisplatin eligible.

The FDA has given Priority Review to a supplemental Biologics License Application (sBLA) for the combination therapy of enfortumab vedotin-ejfv (Padcev; Astellas Pharma Inc., Seagen Inc.) plus pembrolizumab (Keytruda; Merck) as a first line treatment for patients with locally advanced or metastatic urothelial cancer (la/mUC), according to a recent Astellas press release. The review is based on results from the phase 3 EV-302 (NCT04223856) study and a target action date is set for May 9, 2024.

“Chemotherapy has been the standard of care for over 30 years…[and] these patients have a critical need for innovative new therapies,” said Astellas Senior Vice President, Ahsan Arozullah, MD, MPh, Head of Oncology Development, in the press release.

Silver Spring, MD, USA - June 25, 2022: The FDA White Oak Campus, headquarters of the United States Food and Drug Administration, a federal agency of the Department of Health and Human Services (HHS).

Image credit: Tada Images | stock.adobe.com

Annually, approximately 573,000 new cases of bladder cancers are reported around the world and UC makes up 90% of all bladder cancers. Up to 12% of patients may be initially diagnosed with locally advanced disease (cancer that has spread to other organs and muscles) or metastatic disease (meaning it has spread to other parts of the body), which are associated with fast progression and poor long-term survival outcomes.

The open-label, randomized, and controlled phase 3 EV-302 trial is evaluating enfortumab vedotin-ejfv with pembrolizumab against chemotherapy as treatment in patients with untreated la/mUC and are eligible for chemotherapy (cisplatin- or carboplatin-based). The trial included 886 patients, and none were not excluded based on programmed death-ligand 1 (PD-L1) status.

The primary endpoints, which include overall survival (OS) and progression-free survival (PFS) in accordance with RECIST v1.1 and were assessed by blinded independent central review, were met, with the combination therapy significantly extending OS and PFS compared to chemotherapy. EV-302 secondary endpoints included overall response rate (ORR) and duration of response (DOR, and safety.

Some of the most common adverse events (AEs) associated with enfortumab vedotin-ejfv include skin conditions (i.e., rash, dry skin), gastrointestinal issues (decreased appetite, nausea), increased aspartate aminotransferase, glucose, creatinine, and fatigue, decreased lymphocytes, and peripheral neuropathy.

Enfortumab vedotin-ejfv is a first-in-class antibody-drug conjugate (ADC) that binds to cancer cells that express the Nectin-4 protein. Data suggest that, upon binding, the ADC releases an anti-tumor agent called monomethyl auristatin E (MMAE), which may eventually cause cancer-cell apoptosis (programmed cell death).

This drug combination received Breakthrough Therapy designation in 2020. In 2022, the FDA granted Priority Review based on the results of EV-103, and it received accelerated approval for the treatment of this patient population in April 2023.

EV-302 aims to expand the combination’s indication to include cisplatin-eligible patients. It is also meant to confirm findings that supported accelerated approval; thus, if the application is approved, the accelerated approval will become standard approval as a firstline therapy for patients with la/mUC, Arozullah said.

The FDA’s acceptance of our application is a critical step in our work as we seek to deliver this combination to more patients who currently have few treatment options at the advanced stage,” said Roger Dansey, MD, President, Research and Development, Seagen, in the press release.


FDA Grants Priority Review for Supplemental Biologics License Application (sBLA) of PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® (pembrolizumab) for First-Line Treatment of Advanced Bladder Cancer. Astellas. December 1, 2023. Accessed on December 1, 2023. https://www.astellas.com/en/news/28736

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