China’s NMPA Accepts BLA for Enfortumab Vedotin in Locally Advanced/Metastatic Urothelial Cancer

The Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted the biologics license application (BLA) for enfortumab vedotin-ejfv (Padcev) for the treatment of patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1/L1 inhibitor and platinum-based chemotherapy.¹

The BLA is based on findings from the single-arm, open-label, multicenter phase 2 EV-203 trial (NCT04995419), which evaluated enfortumab vedotin in Chinese patients with locally advanced or metastatic urothelial cancer who previously received a PD-1/L1 inhibitor and platinum-based chemotherapy. Results showed that treatment with enfortumab vedotin produced a statistically significant improvement in objective response rate (ORR)––the primary end point––by independent review committee compared with historical controls.

“In China, there were nearly 86,000 new cases of bladder cancer in 2020, and we are working with the NMPA to seek approval for enfortumab vedotin for patients with advanced stage disease,” Ahsan Arozullah, MD, MPH, senior vice president and head of Development Therapeutic Areas at Astellas, said in a press release. “Enfortumab vedotin has become a second- and third-line treatment option for many patients around the world with previously treated locally advanced or metastatic urothelial cancer, and an approval in China may bring this therapy to those patients.”

EV-203 enrolled 40 patients in China. Additional results showed comparable efficacy and pharmacokinetic data between the trial and global data.

The agent is also under study in the phase 3 EV-301 (NCT03474107) and phase 2 EV-201 (NCT03219333) trials. EV-301 is a global, multicenter, open-label, randomized trial comparing enfortumab vedotin with physician’s choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in 608 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and platinum-based chemotherapy.

The primary end point is overall survival, and secondary end points include progression-free survival (PFS), ORR, duration of response (DOR), disease control rate, safety/tolerability, and quality of life.

EV-201 is a single-arm, multi-cohort, multicenter, pivotal trial evaluating enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor in addition to platinum-containing chemotherapy (cohort 1) and those who have not received platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (cohort 2). The trial enrolled 125 patients in cohort 1 and 89 patients in cohort 2 at multiple centers internationally.

The primary end point is confirmed ORR per blinded independent central review. Secondary end points include assessments of DOR, disease control rate, PFS, overall survival, safety, and tolerability.

Notably, results from the EV-301 trial and cohort 2 of the EV-201 trial served as the basis for the full and supplemental approval of enfortumab vedotin by the FDA in July 2021.² Additionally, results from EV-301 and cohort 1 of EV-201 supported the marketing authorization applications for enfortumab vedotin in the European Union, Japan, and Singapore.³

References

1. Astellas and Seagen announce China’s National Medical Products Administration accepts biologics license application for enfortumab vedotin in certain patients with locally advanced or metastatic urothelial cancer. News release. Astellas Pharma. March 9, 2023. Accessed March 10, 2023. https://investor.seagen.com/press-releases/news
2. US FDA grants approval and expands indication for PADCEV (enfortumab vedotin-ejfv) for patients with locally advanced or metastatic urothelial cancer. News release. Seagen Inc. and Astellas Pharma Inc. July 9, 2021. Accessed July 9, 2021. https://investor.seagen.com/press-releases/
3. European Medicines Agency accepts marketing authorization application for enfortumab vedotin. News release. Astellas Pharma Inc. and Seagen Inc. March 26, 2021. Accessed March 26, 2021. https://investor.seagen.com/press-releases/news-details/