Enfortumab Vedotin Combo Approved in China for Advanced Bladder Cancer

The approval is based on findings from the phase 3 EV-302 trial (NCT04223856), which showed that the combination of enfortumab vedotin and pembrolizumab showed a statistically significant and clinically meaningful improvement in progression-free survival and overall survival in patients with previously untreated disease compared with platinum-containing chemotherapy.

China’s National Medical Products Administration (NMPA) granted approval to the combination of enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) as a treatment for adult patients with locally advanced or metastatic urothelial cancer, according to a press release from the developer, Astellas Pharma Inc.¹

The approval is based on findings from the phase 3 EV-302 trial (NCT04223856), which showed that the combination of enfortumab vedotin and pembrolizumab showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) and overall survival (OS) in patients with previously untreated disease compared with platinum-containing chemotherapy. Here, the median PFS was 12.5 months (95% CI, 10.4-16.6) with enfortumab vedotin and 6.3 months (95% CI, 6.2-6.5) with chemotherapy, leading to a 55% reduction in the risk of disease progression or death (HR, 0.45; 95% CI, 0.38-0.54; P <.00001).^2,3

The median OS was 31.5 months (95% CI, 25.4-not reached) vs 16.1 months (95% CI, 13.9-18.3) with enfortumab vedotin plus pembrolizumab and chemotherapy, respectively (HR, 0.47; 95% CI, 0.38-0.58; P <.00001).

"The NMPA approval of enfortumab vedotin in combination with pembrolizumab is the first non-platinum treatment for Chinese patients with advanced urothelial cancer that can be used in the first-line setting,” lead EV-302 investigator in China and professor Guo Jun, who also serves as director of the Department of Urologic Oncology and Melanoma/Sarcoma in Beijing Cancer Hospital, China, stated in a news release.¹ “The results of the EV-302 study demonstrate that this combination nearly doubled median [OS] and increased median [PFS], overall response rate [ORR] and complete response rate compared [with] platinum-based chemotherapy.”

Developers designed enfortumab vedotin as an antibody drug conjugate that targets Nectin-4, a protein highly expressed on the surface of cells in bladder cancer.

In December 2023, the FDA approved enfortumab vedotin plus pembrolizumab for patients with locally advanced or metastatic urothelial cancer, also based on the EV-302 study.⁴

In the ongoing, open-label, controlled phase 3 EV-302 trial, investigators are comparing enfortumab vedotin plus pembrolizumab with platinum-containing chemotherapy in 886 patients with previously untreated locally advanced or metastatic urothelial cancer. Patients are eligible for cisplatin- or carboplatin-containing chemotherapy, regardless of PD-L1 status.

The coprimary end points are PFS and OS per RECIST v1.1 criteria by blinded independent central review (BICR); key secondary outcome measures are ORR by RECIST v1.1 criteria by BICR, duration of response by RECIST v1.1 by BICR, and safety.

Additional data showed that safety results were comparable with those previously reported with this treatment combination. No new safety issues were identified.

Prior safety findings showed that the most common grade 3 or higher treatment-related adverse events with the combination, occurring in at least 3% of patients, comprised maculopapular rash, hyperglycemia, neutropenia, peripheral sensory neuropathy, diarrhea, and anemia.

"The current first-line treatment strategy for advanced urothelial carcinoma in China is platinum-based chemotherapy, with very limited clinical options available,” lead primary EV-302 investigator in China Huang Jian, who also serves as chairman of the Urology Subcommittee of the Chinese Medical Association in the Department of Urology at Sun Yat-sen Memorial Hospital of Sun Yat-sen University in Guangzhou, China, also stated in the news release.¹ “The approval of enfortumab vedotin in combination with pembrolizumab represents the first treatment regimen in the past 20 to 30 years that has shown superiority over platinum-based chemotherapy in the entire population. We hope that this combination could become the future standard-of-care treatment."

References

1. China's National Medical Products Administration (NMPA) Approves PADCEV™ in combination with KEYTRUDA® (pembrolizumab) for the Treatment of Advanced Bladder Cancer. Astellas Pharma. News release. January 8, 2025. Accessed January 9, 2025. https://www.prnewswire.com/news-releases/chinas-national-medical-products-administration-nmpa-approves-padcev-in-combination-with-keytruda-pembrolizumab-for-the-treatment-of-advanced-bladder-cancer-302345641.html
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):S1254-S1335. doi:10.1016/S0923-7534(23)04149-2
3. Powles TB, Valderrama BP, Gupta S, et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer. N Eng J Med. 2024;390(10):875-888. doi:10.1056/NEJMoa2312117
4. FDA approves enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial cancer. News release. FDA. December 15, 2023. Accessed January 9, 2025. https://bit.ly/48ls9bi