Priority Review Granted to Two Applications for Enfortumab Vedotin in Metastatic Urothelial Carcinoma


Based on results from the EV-301 and EV-201 trials, 2 separate applications for enfortumab vedotin as therapy for certain patients with previously treated metastatic urothelial carcinoma were accepted by the FDA and granted priority review.

Two supplemental biologics license applications for enfortumab vedotin (Padcev) have been accepted by the FDA and granted priority review for the treatment of locally advanced or metastatic urothelial carcinoma, announced Astellas Pharma, Inc. and Seagen Inc. who are responsible for developing the agent.1

The first application seeks to convert the current accelerated approval in the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/PD-L1 inhibitor and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting to a full approval based on results of the phase 3 EV-301 trial (NCT03474107).

The second application is based on results of the pivotal cohort 2 of the phase 2 EV-201 trial (NCT03219333) and seeks to expand the current indication to include patients who’ve previously been treated with a PD-1/PD-L1 inhibitor but are not eligible for cisplatin. The target action date for both applications is August 17, 2021.

“These FDA filings, along with regulatory submissions outside of the United States under our collaboration with Astellas, are important steps in our shared goal of bringing [enfortumab vedotin] to more patients with advanced urothelial cancer,” Roger Dansey, MD, chief medical officer of Seagen, said in a press release.

Data from the EV-301 demonstrated that patients receiving enfortumab vedotin (n = 301) had significantly prolonged survival versus those receiving investigator-chosen chemotherapy (n = 307). Median overall survival (OS) in each group was 12.88 months and 8.97 months, respectively (HR, 0.70; 95% CI, 0.56-0.89; P = .001). Progression-free survival times were also superior with enfortumab vedotin with a median of 5.55 months versus 3.71 months with chemotherapy (HR, 0.62; 95% CI, 0.51-0.75; P <.001).2

The confirmed overall response rate (ORR) was higher with enfortumab vedotin at 40.6% versus 17.9% with chemotherapy (P <.001). Fourteen patients in the enfortumab vedotin group had a complete response (4.9%) versus 8 patients (2.7%) in the chemotherapy group.

Both groups had a high overall rate of treatment-related adverse events, at 93.9% for enfortumab vedotin and 91.8% for chemotherapy, with grade 3 or greater occurring in 51.4% and 49.8%, respectively. Dose reductions, treatment interruptions, or withdrawal due to treatment-related adverse events occurred in 32.4%, 51.0%, and 13.5% of patients receiving enfortumab vedotin, respectively, and in 27.5%, 18.9%, and 11.3% with chemotherapy, respectively.

Data from cohort 2 of EV-201 were presented during the 2021 Genitourinary Cancers Symposium.3 Eligible patients had locally advanced unresectable or metastatic urothelial carcinoma, were previously treated with a PD-1/PD-L1 inhibitor, and were ineligible for cisplatin-containing chemotherapy. They had no prior exposure to platinum-containing chemotherapy in the locally advanced or metastatic setting.

In this cohort of patients, the ORR was 52% (95% CI, 40.8%-62.4%), with roughly 20% of patients having a complete response to therapy. Subgroup analyses showed response rates were seen consistently in tumors of the upper tract (ORR = 61%), in patients with liver metastasis (ORR = 48%), and in those who did not respond to prior PD-1/PD-L1 inhibitors (ORR = 48%).

Both applications are under review as part of the Real-Time Oncology Review pilot program. Under Project Orbis, a global collaborative review program, health authorities in Australia and Canada are also evaluating data from both trials. Regulatory submissions in Japan and the European Union had been previously announced.

“With our recent regulatory submissions, we intend to provide the highest level of clinical evidence supporting [enfortumab vedotin] use, overall survival data from a randomized phase 3 trial, and expand availability in multiple countries where there is unmet medical need,” Andrew Krivoshik, MD, PhD, senior vice president and Oncology Therapeutic Area Head of Astellas, said in a press release.


1. Astellas and Seagen Announce U.S. FDA Acceptance of Two Supplemental Biologics License Applications for PADCEV® (enfortumab vedotin-ejfv) in Locally Advanced or Metastatic Urothelial Cancer. News release. Astellas Pharma, Inc. and Seagen Inc. April 19, 2021. Accessed April 19, 2021.

2. Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N Engl J Med. 2021;384(12):1125-1135. doi: 10.1056/NEJMoa2035807

3. Balar AV, McGregor BA, Rosenberg JE, et al. EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors. J Clin Oncol. 2021;39(suppl 6).394. doi: 10.1200/JCO.2021.39.6_suppl.394

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