FDA Grants Priority Review to sBLA for Enfortumab Vedotin Plus Pembrolizumab in Advanced Urothelial Cancer

The FDA has granted priority review to a supplemental biologics license application (sBLA) for enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) for the frontline treatment of patients with locally advanced or metastatic urothelial cancer.¹

The designation is based on findings from the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856), which demonstrated that the combination led to a statistically significant improvement in overall survival (OS) and progression-free survival (PFS) compared with platinum-containing chemotherapy in patients with previously untreated locally advanced or metastatic urothelial cancer.² Additionally, the safety profile of the regimen was in line with that previously reported with the combination, and no new safety signals occurred.¹

The target action date is May 9, 2024, under the Prescription Drug User Fee Act. If approved, the combination would be the first treatment regimen for patients with previously untreated locally advanced or metastatic urothelial cancer regardless of cisplatin eligibility.

“Through our clinical development program, data have consistently shown the impact of combining enfortumab vedotin with pembrolizumab for advanced bladder cancer. The FDA’s acceptance of our application is a critical step in our work as we seek to deliver this combination to more patients who currently have few treatment options at the advanced stage,” Roger Dansey, MD​, president of Research and Development at Seagen​, stated in a news release.

In February 2020, the combination received breakthrough therapy designation from the FDA as frontline therapy for cisplatin-ineligible patients³ and by December 2022, the sBLA for the regimen had received priority review designation for this population.⁴ In April 2023, the FDA granted accelerated approval to the combination for the treatment of adult patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-containing chemotherapy based on response rate and durability of response data from the phase 1b/2 EV-103/KEYNOTE-869 trial (NCT03288545).⁵

The EV-302 trial was designed to serve as the confirmatory trial for the US accelerated approval and the basis for other global regulatory submissions as well as support the expanded indication into the cisplatin-eligible patient population.

“We look forward to the FDA’s review of this application, which, if approved, will convert the accelerated approval of the combination based on results from the EV-103 study to standard approval for all first-line locally advanced or metastatic urothelial cancer patients, expanding the indication to cisplatin eligible patients. These patients have a critical need for innovative new therapies, as chemotherapy has been the standard of care for over 30 years. We are committed to delivering on our goal of helping patients with advanced urothelial cancer live longer,” Ahsan Arozullah, MD, MPH, senior vice president and head of Oncology Development at Astellas​, said.

The combination of enfortumab vedotin and pembrolizumab is also under investigation in patients with muscle-invasive bladder cancer in the phase 3 EV-304/KEYNOTE-B15 (NCT04700124) and EV-303/KEYNOTE-905 (NCT03924895) trials.

Additionally, the open-label, multicenter, multi-cohort, phase 2 EV-202 trial (NCT04225117) is evaluating enfortumab vedotin alone in patients with previously treated advanced solid tumors. The study also has a cohort that is evaluating enfortumab vedotin plus pembrolizumab in patients with previously untreated recurrent or metastatic head and neck squamous cell carcinoma.

References

1. FDA grants priority review for supplemental biologics license application (sBLA) of PADCEV (enfortumab vedotin-ejfv) with KEYTRUDA (pembrolizumab) for first-line treatment of advanced bladder cancer. News release. Seagen and Astellas. November 30, 2023. Accessed December 1, 2023. https://investor.seagen.com/press-releases/news-details/2023/FDA-Grants-Priority-Review-for-Supplemental-Biologics-License-Application-sBLA-of-PADCEV-enfortumab-vedotin-ejfv-with-KEYTRUDA-pembrolizumab-for-First-Line-Treatment-of-Advanced-Bladder-Cancer/default.aspx
2. Powles TB, Valderrama BP, Gupta S, et al. EV-302/KEYNOTE-A39: open-label, randomized phase III study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC). Ann Oncol. 2023;34(suppl 2):S1340. doi:10.1016/j.annonc.2023.10.106
3. Astellas and Seattle Genetics receive FDA breakthrough therapy designation for PADCEV (enfortumab vedotin-ejfv) in combination with pembrolizumab in first-line advanced bladder cancer. News release. Astellas Pharma Inc. and Seattle Genetics, Inc. February 19, 2020. Accessed December 1, 2023. https://www.prnewswire.com/news-releases/astellas-and-seattle-genetics-receive-fda-breakthrough-therapy-designation-for-padcev-enfortumab-vedotin-ejfv-in-combination-with-pembrolizumab-in-first-line-advanced-bladder-cancer-301007506.html
4. 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, and Merck. December 20, 2022. Accessed December 1, 2023. https://investor.seagen.com/press-releases/news-details/2022/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/default.aspx
5. FDA grants accelerated approval to enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial carcinoma. FDA. April 3, 2023. Accessed December 1, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/