FDA Approves Enfortumab Vedotin for Metastatic or Advanced Urothelial Cancer

The FDA granted accelerated approval to enfortumab vedotin-ejfv for the treatment of adult patients with locally advanced or metastatic urothelial cancer.

The FDA granted accelerated approval to enfortumab vedotin-ejfv (Padcev) for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have received prior treatment with a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy.

Of note, this is the first drug approved for this patient population.

“Metastatic urothelial cancer is an aggressive and devastating disease with limited treatment options, and the approval of Padcev is a significant advance for these patients who previously had limited options after initial therapies failed,” Jonathan E. Rosenberg, MD, medical oncologist, chief, genitourinary medical oncology service, Memorial Sloan Kettering Cancer Center, said in a press release.

The approval is based on results from the ongoing phase II EV-201 trial, which showed that enfortumab vedotin – a novel investigational antibody-drug conjugate that targets Nectin-4, a protein that is highly expressed in urothelial cancers – elicited an overall response rate (ORR) of 44% in patients with locally advanced or metastatic urothelial cancer, which included a 12% complete response rate, and a 32% partial response rate.

RR per blinded independent central review served as the primary endpoint of the study, while secondary endpoints included duration of response (DOR), disease control rate, progression-free survival (PFS), overall survival (OS), safety, and tolerability.

“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,” 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, said in statement. “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.”

Additional results showed that the OS was 11.7 months (95% CI, 9.1–not reached), the median PFS was 5.8 months (95% CI, 4.9-7.5), and the median DOR was 7.6 months (range, 0.95-11.30+).

The most common treatment-related adverse events (TRAEs) of any grade were fatigue (50%), alopecia (49%), and decreased appetite (44%), while TRAEs of interest include any case of rash (all grade, 48%; grade ≥3, 12%), any peripheral neuropathy (all grade, 50%; grade ≥3, 3%), and any hyperglycemia (all grade, 11%; grade ≥3, 6%).

The first-in-class antibody-drug conjugate is approved under the FDA’s Accelerated Approval Program, which allows approval of a medicine based on a surrogate endpoint if the medicine fills an unmet medical need for a serious condition. In this instance, the accelerated approval was based on tumor response rate.

Continued approval will be contingent upon further evaluation to verify and describe the clinical benefit of the drug in a confirmatory trial.


Seattle Genetics and Astellas Announce US FDA Grants Priority Review for Enfortumab Vedotin Biologics License Application in Locally Advanced or Metastatic Urothelial Cancer. Seattle Genetics. Published September 16, 2019. https://bit.ly/2mbJ9Ps. Accessed September 16, 2