FDA Accepts sBLAs for Enfortumab Vedotin/Pembrolizumab in Advanced or Metastatic Urothelial Cancer

The FDA has set the Prescription Drug User Fee Act date for April 21, 2023 for each supplemental biologics license application of enfortumab vedotin-ejfv and pembrolizumab in urothelial carcinoma.

The FDA has granted priority review to supplemental biological license applications for enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) for use as a combination therapy in locally advanced or metastatic urothelial cancer for those who are ineligible to receive cisplatin-based chemotherapy, according to a press release from Seagen, Astellas Pharma, and Merck.1

The applications for the agents were supported by efficacy and safety findings from cohort A and cohort K from the phase 1b/2 EV-103 or KEYNOTE-869 trial (NCT03288545). Results from cohort K were shared during a session at the 2022 European Society for Medical Oncology (ESMO) Congress.2

Findings from cohort K of the trial indicated that the most common treatment-related adverse effects (TEAEs) among 76 patients treated with enfortumab vedotin plus pembrolizumab included fatigue (56.6%), peripheral sensory neuropathy (51.3%), and alopecia (46.1%).

Investigators reported a confirmed objective response rate (ORR) of 64.5% with a complete response (CR) rate of 10.5% among those treated with enfortumab vedotin and pembrolizumab vs 45.2% and 4.1% in the enfortumab vedotin monotherapy arm. A total of 85.7% of responses were reported at 9±1 weeks. Additionally, the median duration of response (DOR) was not reached in the combination arm vs 13.2 months in the monotherapy arm.

The median overall survival (OS) was 22.3 months and 21.7 months, respectively. Moreover, the median progression-free survival (PFS) was not reached and 8.0 months in each respective arm.

The FDA has set a Prescription Drug User Fee Act date of April 21, 2023 for each application.

“We look forward to working closely with the FDA as we seek potential accelerated approval for this combination in the hopes that it can be another treatment option for patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-containing chemotherapy,” Ahsan Arozullah, MD, MPH, senior vice president and head of Development Therapeutic Areas at Astellas, said in the press release.

The ongoing, multi-cohort, open-label phase 1b/2 EV-103 study evaluated enfortumab vedotin on its own and in combination with pembrolizumab and/or chemotherapy as a first- or second-line treatment for patients with locally advanced or metastatic urothelial cancer.

Patients were treated with enfortumab vedotin at a dose of 1/25 mg/kg intravenously on day 1 of every 3-week cycle. Patients in the dose escalation (n = 5) and expansion cohorts (n = 40) also received pembrolizumab. Moreover, cohort K (n = 151) had the option of receiving the combination regimen or enfortumab vedotin monotherapy.

Primary end points of the EV-103 study included confirmed ORR per RECIST v1.1 criteria by investigator assessment, with key secondary end points including confirmed ORR, disease control rate, DOR, PFS, OS, and safety.

Patients 18 years and older with histologically documented locally advanced or metastatic urothelial cancer were eligible to enroll on the trial. Additional inclusion criteria included having an ECOG performance status of 0 to 2.

Patients were unable to enroll on the trial if they had received any prior treatment with a PD-1, PD-L1, or PD-L2 inhibitor, or with stimulatory T-cell receptor agents such as CD137 agonists or OX-40 agonists. Patients were also unsuitable for enrollment if they had any grade 2 or higher sensory or motor neuropathy, active central nervous system metastases, ongoing grade 2 or higher treatment-related AEs, or received any prior treatment with enfortumab vedotin.

Enfortumab vedotin was previously approved by the FDA for use in adult patients with locally advanced or metastatic urothelial cancer following prior treatment with a PD-1 or PD-L1 inhibitor in July 2021.3


  1. Seagen, Astellas and Merck announce FDA acceptance of sBLAs for PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® (pembrolizumab) for the first-line treatment of certain patients with locally advanced or metastatic urothelial cancer. News release. Seagen, Astellas, Merck. December 20, 2022. Accessed December 20, 2022. bwnews.pr/3G8qriv
  2. Rosenberg JE, Milowsky M, Ramaurthy C, et al. Study EV-103 Cohort K: antitumor activity of enfortumab vedotin (EV) monotherapy or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC). Ann Oncol. 2022;33(suppl 7):S808-S869. doi:10.1016/annonc/annonc1089
  3. FDA grants regular approval to enfortumab vedotin-ejfv for locally advanced or metastatic urothelial cancer. News release. FDA. July 9, 2021. Accessed December 20, 2022. https://bit.ly/3hsvrln

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