China NMPA Accepts sBLA for Enfortumab Vedotin Plus Pembrolizumab in Advanced Bladder Cancer
核心洞察
China's NMPA has accepted the sBLA for enfortumab vedotin with pembrolizumab as first-line treatment for locally advanced or metastatic urothelial cancer (搜索).
The application is based on the EV-302 trial, which showed significant improvements in overall and progression-free survival compared to chemotherapy.
If approved, this combination would be the first alternative to platinum-based chemotherapy for this patient population in China.
Astellas and Pfizer announced that the China National Medical Products Administration (NMPA) has accepted the supplemental Biologics License Application (sBLA) for enfortumab vedotin in combination with KEYTRUDA® (pembrolizumab) for the first-line treatment of adult patients with previously untreated locally advanced or metastatic urothelial cancer (搜索) (la/mUC). This decision marks a significant step toward providing a new treatment option for a patient population with limited alternatives to chemotherapy. If approved, enfortumab vedotin with KEYTRUDA would be the first combination treatment in China to offer an alternative to platinum-containing chemotherapy, the current standard of care in the first-line setting. The U.S. Food and Drug Administration approved the combination therapy in December 2023. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency is reviewing the enfortumab vedotin in combination with pembrolizumab therapy, as well as Japan’s Ministry of Health, Labour and Welfare (MHLW).
The sBLA is based on the results of the Phase 3 EV-302 clinical trial (also known as KEYNOTE-A39), which demonstrated statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) compared to platinum-containing chemotherapy in patients with previously untreated la/mUC. The safety profile observed in the trial was consistent with previous reports for this combination, with no new safety concerns identified.
Clinical Significance
Professor Guo Jun, lead PI in China for the EV-302 trial, highlighted the importance of this development, stating, "In China, the recommended first-line treatment for advanced urothelial cancer (搜索) is platinum-based chemotherapy, and there are currently no other treatments approved in the first-line setting... 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 progression-free survival, and significantly improve the overall survival benefit of patients with locally advanced or metastatic urothelial cancer compared to chemotherapy."
About the EV-302 Trial
The EV-302 trial is an open-label, randomized, controlled Phase 3 study that evaluated enfortumab vedotin in combination with pembrolizumab versus platinum-containing chemotherapy in 886 patients with previously untreated la/mUC who were eligible for cisplatin- or carboplatin-containing chemotherapy, regardless of PD-L1 status. The dual primary endpoints of the trial were OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included ORR per RECIST v1.1 by BICR, DOR per RECIST v1.1 by BICR, and safety. Findings from EV-302 were presented at the European Society for Medical Oncology (ESMO) Congress 2023 in October 2023.
Urothelial Cancer Burden
Urothelial cancer (搜索), which accounts for 90% of all bladder cancers, affects the bladder, urethra, ureters, and renal pelvis. Approximately 12% of cases are locally advanced or metastatic at diagnosis. Globally, there are approximately 614,000 new cases of bladder cancer (搜索) and 220,000 deaths annually. In China, it is estimated that approximately 93,000 people were diagnosed with bladder cancer and approximately 41,000 deaths were reported in 2022.
About Enfortumab Vedotin
Enfortumab vedotin is a first-in-class antibody-drug conjugate (ADC) that targets Nectin-4 (搜索), a protein highly expressed in bladder cancer (搜索). Nonclinical data suggest that enfortumab vedotin's anticancer activity results from its binding to Nectin-4-expressing cells, followed by internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE), leading to cell cycle arrest and apoptosis.