Investigational Drug for Previously-Treated Advanced Urothelial Cancer Shows Positive Results


Enfortumab vedotin is being investigated for the treatment of locally advanced or metastatic urothelial cancer following both platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor.

In an ongoing phase 2 clinical trial, the investigational drug enfortumab vedotin achieved positive topline results for the treatment of patients with previously-treated locally advanced or metastatic urothelial cancer, according to Seattle Genetics.

The EV-201 clinical trial is a phase 2 single-arm study evaluating the therapy in patients with locally advanced or metastatic urothelial cancer who have received previous treatment with both platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor. The FDA previously granted Breakthrough Therapy designation to enfortumab vedotin based on preliminary results from the phase 1 trial EV-101 for patients whose disease has progressed during or following treatment with a PD-1 or PD-L1 inhibitor.

Enfortumab vedotin is an investigational antibody-drug conjugate (ADC) that targets Nectin-4, a therapeutic target that is highly expressed in multiple solid tumors including urothelial cancers. Urothelial cancer accounts for 90% of bladder cancer cases, with more than 82,000 individuals diagnosed with bladder cancer in the United States in 2018, according to the press release. Currently, there are no approved therapies for metastatic urothelial cancer once it has progressed after chemotherapy and a PD-1 or PD-L1 inhibitor.

The phase 2 trial includes 2 cohorts, with cohort 1 comprised of patients previously treated with a platinum-containing chemotherapy and cohort 2, which is continuing enrollment, including patients who have not received a platinum-containing chemotherapy and are ineligible for cisplatin.

According to the results, the study showed a 44% objective response rate per blinded independent central review, with a duration of response that was consistent with what was reported in the previous phase 1 study. The most common treatment-related adverse effects in the trial were fatigue, alopecia, decreased appetite, rash, and peripheral neuropathy.

“Despite recent approvals of multiple checkpoint inhibitors for previously treated locally advanced or metastatic urothelial cancer, there remains a high unmet need for effective treatments upon progression after initial chemotherapy and immunotherapy,” Roger Dansey, MD, chief medical officer at Seattle Genetics, said in a statement. “These results for enfortumab vedotin indicate it may be able to help patients whose urothelial cancer progresses following treatment with standard chemotherapy and a PD-1 or PD-L1 inhibitor.”

According to Seattle Genetics, the company expects to submit a Biologics License Application later this year. A confirmatory phase 3 study is also ongoing to support global registration.


Seattle Genetics and Astellas Announce Positive Topline Results from Pivotal Trial of Enfortumab Vedotin in Locally Advanced or Metastatic Urothelial Cancer [news release]. Seattle Genetics. Accessed March 28, 2019.

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