Enfortumab Vedotin Combo Earns Priority Review in Japan for Bladder Cancer

The FDA granted approval to enfortumab vedotin/pembrolizumab as a treatment for patients with locally advanced or metastatic urothelial cancer in December 2023.

Japan’s Ministry of Health, Labour, and Welfare (MHLW) has granted priority review to a supplemental biologics license application (sBLA) for enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab (Keytruda) as a frontline treatment for adult patients with previously untreated locally advanced or metastatic urothelial cancer, according to a press release from Astellas Pharma.¹

Supporting data for the sBLA in this indication came from the phase 3 EV-302 trial (NCT04223856).

According to previously published findings, the median progression-free survival (PFS) was 12.5 months in patients who received enfortumab vedotin plus pembrolizumab compared with 6.3 months in those who were treated with chemotherapy (HR, 0.45; 95% CI, 0.38-0.54; P <.00001).² Additionally, the median overall survival (OS) in each respective arm was 31.5 months vs 16.1 months (HR, 0.47; 95% CI, 0.38-0.58; P <.00001), and the confirmed overall response rates (ORRs) were 67.7% vs 44.4%.

Subgroup analysis findings from the EV-302 trial were also presented at the 2024 Genitourinary Cancers Symposium. Data highlighted a PFS benefit with enfortumab vedotin plus pembrolizumab compared with chemotherapy in those with visceral metastases (HR, 0.45; 95% CI, 0.37-0.55) and lymph node-only disease (HR, 0.40; 95% CI, 0.26-0.62).³ Additionally, the experimental combination produced an OS benefit in patients with visceral metastases (HR, 0.47; 95% CI, 0.37-0.60) and those without (HR, 0.46; 95% CI, 0.27-0.78).

Safety data in the EV-302 trial were comparable with prior reports of enfortumab vedotin and pembrolizumab. Additionally, investigators identified no new safety signals.

“The MHLW’s priority review for our application for [enfortumab vedotin] in combination with pembrolizumab reflects the significance of the EV-302 trial findings and the urgent need for innovative new treatment options,” Ahsan Arozullah, MD, MPH, senior vice president and head of Oncology Department at Astellas, said in the press release.¹ “We are pleased by this review designation and hope to quickly bring this treatment option to those who need it most.”

In the open-label phase 3 EV-302 trial, 886 patients were randomly assigned to receive enfortumab vedotin at 1.25 mg/kg intravenously on days 1 and 8 plus pembrolizumab at 200 mg intravenously on day 1 of every 3-week cycle or gemcitabine plus cisplatin or carboplatin.

The trial’s dual primary end points were PFS based on RECIST v1.1 criteria via blinded independent central review and OS. Secondary end points included ORR and safety.

The EV-302 trial is part of a clinical program assessing enfortumab vedotin plus pembrolizumab as a treatment for patients with urothelial cancer and other solid tumors. The ongoing, muti-cohort, open-label phase 1b/2 EV-103 trial (NCT03288545) is investigating enfortumab vedotin alone or with pembrolizumab and/or chemotherapy among patients with locally advanced or metastatic urothelial cancer and those with muscle-invasive bladder cancer.

The FDA granted approval to enfortumab vedotin/pembrolizumab as a treatment for patients with locally advanced or metastatic urothelial cancer in December 2023.⁴ Supporting data for the approval came from the EV-302 trial.

The European Medicines Agency (EMA) validated a type II application for the enfortumab vedotin combo for the same patient population in January 2024.⁵ The designation was also based on findings from the EV-302 trial.

“Patients in Europe need better treatment options for advanced stage urothelial cancer, and we look forward to working with the EMA on their review of the combination of enfortumab vedotin and pembrolizumab,” Arozullah said in a press release at the time the EMA validated the application.⁵ “If approved, the combination would be the first alternative to a chemotherapy-based treatment for this patient population. This milestone is another opportunity to affirm our commitment to helping patients with advanced urothelial cancer live longer.”

References

1. PADCEV™ (enfortumab vedotin (genetical recombination)) with KEYTRUDA® (pembrolizumab (genetical recombination)) granted priority review by Japan’s Ministry of Health, Labour and Welfare for first-line treatment of advanced bladder cancer. News release. Astellas Pharma Inc. February 16, 2024. Accessed February 19, 2024. http://tinyurl.com/7wuk5ybv
2. Powles TB, Perez Valderrama B, 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. Van Der Heijden M, Powles T, Gupta S, et al. Enfortumab vedotin (EV) in combination with pembrolizumab (P) versus chemotherapy in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC): subgroup analyses results from EV-302, a phase 3 global study. J Clin Oncol. 2024;42(suppl 4):LBA530. doi:10.1200/JCO.2024.42.4_suppl.LBA530
4. FDA approves enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial cancer. News release. FDA. December 15, 2023. Accessed February 19, 2024. https://bit.ly/48ls9bi
5. European medicines agency validates type II variation application for PADCEVTM (enfortumab vedotin) with KEYTRUDA®(pembrolizumab) for first-line treatment of advanced bladder cancer. News release. Astellas Pharma Inc. January 26, 2024. Accessed February 19, 2024. http://tinyurl.com/29s9h8dk