Padcev Gets Full Approval, Expanded Indication for Urothelial Cancer

The Food and Drug Administration (FDA) has granted regular approval to Padcev® (enfortumab vedotin-ejfv), a Nectin-4-directed antibody and microtubule inhibitor conjugate, for the treatment of adults with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand (PD-L1) inhibitor and platinum-containing chemotherapy. This indication had previously been granted accelerated approval based on tumor response rate. 

The full approval was based on data from the open-label, randomized, multicenter confirmatory phase 3 EV-301 trial ( Identifier: NCT03474107), which evaluated the efficacy and safety of enfortumab vedotin-ejfv in 608 patients with locally advanced or metastatic urothelial cancer who received a prior PD-1 or PD-L1 inhibitor and platinum-based chemotherapy. Patients were randomly assigned 1:1 to receive either enfortumab vedotin-ejfv 1.25mg/kg intravenously on days 1, 8 and 15 of each 28-day cycle (n=301) or investigator’s choice of single-agent chemotherapy (docetaxel, paclitaxel, or vinflunine; n=307). 

The primary endpoint was overall survival (OS). Key secondary endpoints included progression-free survival (PFS) and overall response rate (ORR) as assessed by an investigator using RECIST v1.1.

At the time of pre-specified interim analysis, median OS was observed to be 12.9 months (95% CI, 10.6-15.2) with enfortumab vedotin-ejfv vs 9 months (95% CI, 8.1-10.7) with chemotherapy (hazard ratio [HR] 0.70; 95% CI, 0.56-0.89; P =.0014). The median PFS was 5.6 months (95% CI, 5.3-5.8) for the enfortumab vedotin-ejfv arm and 3.7 months (95% CI, 3.5-3.9) for the chemotherapy arm (HR 0.62; 95% CI, 0.51-0.75; P <.0001). The ORR was 40.6% (95% CI, 34.9-46.5) with enfortumab vedotin-ejfv vs 17.9% (95% CI, 13.7-22.8) with chemotherapy (P <.0001).

Approval was also granted to the supplemental Biologics License Application (sBLA) for Padcev for the treatment of adults with locally advanced or metastatic urothelial cancer who are ineligible for cisplatin-containing chemotherapy and have previously received 1 or more prior lines of therapy. The sBLA approval was based on data from cohort 2 of the single-arm, multi-cohort phase 2 EV-201 trial ( Identifier: NCT03219333), which included 89 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor, and were cisplatin ineligible and did not receive platinum in the locally advanced or metastatic setting. The primary endpoint was ORR, with duration of response (DOR) being a key secondary endpoint.

After a median follow-up of 16 months, findings showed a confirmed ORR of 51% (95% CI, 39.8-61.3), with 22% of patients achieving complete response and 28% of patients achieving partial response. Median DOR was 13.8 months (95% CI, 6.4-not estimable).

“Almost half of advanced bladder cancer patients cannot receive cisplatin-based chemotherapy,” said Evan Y. Yu, MD, Division of Oncology, Department of Medicine, University of Washington School of Medicine and a lead investigator for the EV-201 trial, in which all patients were previously treated with immunotherapy. “Many of these patients will receive first-line immunotherapy. If their cancer does not respond, or if it progresses after prior response to immunotherapy, there is an urgent need for more treatment options as there is currently no standard of care. A new regulatory approval for enfortumab vedotin is an important clinical advance and can help serve this unmet need.”

As for safety, the prescribing information for Padcev now includes a Boxed Warning describing the risk of serious skin reactions that may occur with therapy (eg, Stevens-Johnson syndrome and toxic epidermal necrolysis). The labeling also warns of the potential for severe, life-threatening or fatal pneumonitis.

Padcev is supplied as 20mg and 30mg of enfortumab vedotin-ejfv as a lyophilized powder in a single-dose vial for reconstitution.


  1. FDA grants regular approval to enfortumab vedotin-ejfv for locally advanced or metastatic urothelial cancer. [press release]. Silver Spring, MD: US Food and Drug Administration; July 9, 2021. 
  2. U.S. FDA grants regular approval and expands indication for Padcev® (enfortumab vedotin-ejfv) for patients with locally advanced or metastatic urothelial cancer. [press release]. Tokyo, Japan and Bothell, WA; Astellas Pharma Inc. and Seagen Inc.; July 9, 2021.
  3. Padcev [package insert]. Northbrook, IL and Bothell, WA: Astellas Pharma Inc. and Seagen Inc.; 2021.