Enfortumab Vedotin Combo Earns Priority Review in China for Bladder Cancer

The FDA approved enfortumab vedotin plus pembrolizumab for patients with locally advanced or metastatic urothelial cancer in December 2023.

The Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted a supplemental biologics license application (sBLA) seeking approval of enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab (Keytruda) as frontline treatment for adult patients with locally advanced or metastatic urothelial cancer, according to a press release from developers Astellas Pharma.¹

Supporting data for the sBLA in this indication came from the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856).

According to findings presented at the 2023 European Society for Medical Oncology (ESMO) Congress, the median overall survival (OS) was 31.5 months (95% CI, 25.4-not reached [NR]) with enfortumab vedotin plus pembrolizumab vs 16.1 months (95% CI, 13.9-18.3) with chemotherapy (HR, 0.47; 95% CI, 0.38-0.58; P <.00001).² OS findings were consistent across all predefined subgroups based on characteristics including cisplatin eligibility and PD-L1 expression status. Additionally, the median progression-free survival (PFS) was 12.5 months (95% CI, 10.4-16.6) vs 6.3 months (95% CI, 6.2-6.5) in each respective arm (HR, 0.45; 95% CI, 0.38-0.54; P <.00001).

Safety findings in the EV-302 trial were comparable with prior reports of the enfortumab vedotin and pembrolizumab combination.

“In China, the recommended first-line treatment for advanced urothelial cancer is platinum-based chemotherapy, and there are currently no other treatments approved in the first-line setting,” Professor Guo Jun, lead primary investigator in China for the EV-302 trial, director of the Department of Melanoma and Urological Oncology at Beijing Cancer Hospital, and executive board member of the Chinese Society Of Clinical Oncology (CSCO), said in the press release.¹

“Given the efficacy brought by chemotherapy, alternate treatment options are extremely needed to extend survival benefits and potentially improve the prognosis of those patients. The results of the EV-302 study demonstrated that enfortumab vedotin in combination with pembrolizumab, as the first non-platinum first-line treatment, can achieve a clinically meaningful improvement in response rate, nearly double the median [PFS], and significantly improve the [OS] benefit of patients with locally advanced or metastatic urothelial cancer compared to chemotherapy.”

In the EV-302 trial, 886 patients with previously untreated locally advanced or metastatic urothelial carcinoma were assigned to receive enfortumab vedotin plus pembrolizumab or platinum-based chemotherapy. The trial’s dual primary end points were OS and PFS based on RECIST v1.1 criteria. Secondary end points included overall response rate, duration of response, and safety.

China’s NMPA also accepted a BLA for enfortumab vedotin monotherapy as a treatment for those with locally advanced or metastatic urothelial carcinoma previously treated with a PD-L1 inhibitor plus platinum-containing chemotherapy earlier in March 2023.³ Supporting data for the BLA in this indication came from the phase 2 EV-203 trial (NCT04995419).

“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 at the time the BLA was accepted.³ “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.”

The FDA approved enfortumab vedotin plus pembrolizumab for patients with locally advanced or metastatic urothelial cancer in December 2023.⁴ Supporting data for the approval in this indication came from the EV-302 trial.

References

1. China's National Medical Products Administration accepts Astellas and Pfizer's supplemental biologics license application for enfortumab vedotin with KEYTRUDA® (pembrolizumab) for first-line treatment of advanced bladder cancer. News release. Astellas Pharma Inc. March 28, 2024. Accessed March 29, 2024. https://tinyurl.com/y5hkzd9t
2. Groundbreaking EV-302 trial significantly extends overall survival and progression-free survival in patients treated with PADCEV® (enfortumab vedotin-ejfv) and KEYTRUDA® (pembrolizumab) in first-line advanced bladder cancer. News release. Astellas Pharma Inc. October 23, 2023. Accessed March 29, 2024. https://tinyurl.com/yy8zjfpu
3. 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 Inc. and Seagen Inc. March 10, 2023. Accessed March 29, 2024. https://tinyurl.com/4s3z2563
4. FDA approves enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial cancer. News release. FDA. December 15, 2023. Accessed March 29, 2024. https://bit.ly/48ls9bi