▎WuXi AppTec Content Team Report

Today (January 8), the official website of China's National Medical Products Administration (NMPA) announced,Submitted by AstellasEnfortumab Vedotin for Injectionand submitted by MSDPembrolizumabThe marketing application for the combination therapy has been approved.According to the previous press release from Astellas, this combination therapy has been approved this time.For the first-line treatment of adult patients with previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC)。

Screenshot source: NMPAOfficial Website

Vientamab is aAntibody-drug conjugates (ADC) targeting Nectin-4, jointly developed by Astellas and Seagen (which has been acquired by Pfizer). Nectin-4 is a protein located on the cell surface and is highly expressed in bladder cancer. Vedotin can bind to cells expressing the Nectin-4 protein, then internalize and release the anti-tumor component monomethyl auristatin E (MMAE) into the cells, causing cell cycle arrest and programmed cell death (apoptosis). In August 2024, vedotin was approved in China.Approved for Marketing, used for treatmentPreviously treated with PD-1/PD-L1 inhibitors and platinum-based chemotherapy for locally advanced or metastatic diseaseUrothelial CarcinomaPatient.

Pembrolizumab is an anti-PD-1 monoclonal antibody developed by Merck. Previously, Astellas and Pfizer jointly signed a clinical cooperation agreement with Merck to evaluate the efficacy of Astellas and Pfizer's enfortumab vedotin combined with Merck's pembrolizumab in treating patients with previously untreated metastatic urothelial carcinoma.U.S. FDA、European Commission (EC)And Japan's Ministry of Health, Labour and Welfare have successively approved this combination therapy forFirst-line treatment for advanced urothelial carcinoma。

According to the press release from Astellas, the sBLA for vedelimumab in combination with pembrolizumab as a first-line treatment for advanced urothelial carcinoma is based on the results of the Phase 3 clinical trial EV-302 (also known as KEYNOTE-A39). The study found that the combination therapy improved overall survival (OS) and progression-free survival (PFS) in previously untreated patients with locally advanced or metastatic urothelial carcinoma (la/mUC), with results showing statistical significance and clinical importance.

• The median overall survival for the combination therapy was31.5 months(vs 16.1 months in the chemotherapy group), that isCompared with the chemotherapy group, the risk of death in patients treated with combination therapy was reduced by 53%.。

• The median progression-free survival period for combination therapy is12.5 months(vs 6.3 months in the chemotherapy group), i.e.Compared with the chemotherapy group, the risk of cancer progression or death in patients treated with combination therapy was reduced by 55%.。

• Consistent overall survival and progression-free survival results were observed in the preset subgroups, including cisplatin tolerance and PD-L1 expression levels.InCisplatin-tolerant subgroup and cisplatin-intolerant subgroup(The numbers of participants were 244 and 198, respectively), the risk of death was reduced by 47% and 57%, respectively, and the risk of disease progression or death was reduced by 52% and 57%, respectively.PD-L1 Low Expression Subgroup and PD-L1 High Expression Subgroup(The death risks for 184 and 254 people were reduced by 56% and 51%, respectively, and the risks of disease progression or death were reduced by 50% and 58%, respectively.)

Astellas' previous press release introduced that the first-line treatment strategy for advanced urothelial carcinoma in China is still platinum-based chemotherapy, with no other approved first-line treatment options available. The effectiveness and progression-free survival of this chemotherapy-based first-line treatment need further improvement. The combination of Vinblastine and Pembrolizumab has the potential to change the existing treatment model and become a combination therapy alternative to platinum-based chemotherapy.。

[1] Drug Approval Certificate Delivery Information on January 8, 2025. From https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20250108154612147.html

[2]AnAstellas and Pfizer's Enfortumab Vedotin Combined with Pembrolizumab for First-Line Treatment of Advanced Bladder Cancer sBLA Accepted by CDE. Retrieved Mar 28, 2024, from https://mp.weixin.qq.com/s/gLNxv-NxAnV27OlJFhNT9A

[3] International Agency for Research on Cancer (IARC). Bladder Fact Sheet. Lyon, France. 2022 (02-2024). Available at: 160-china-fact-sheet.pdf (who.int)

[4] Japan's Ministry of Health, Labour and Welfare approves Padcev (enfortumab vedotin) in combination with Keytruda (pembrolizumab) for first-line treatment of unresectable urothelial carcinoma. Retrieved Sep 26, 2024, from https://mp.weixin.qq.com/s/CIOYAOjO2ijBM4EvaNTmTw

[5FDA Approves PADCEV® in Combination with KEYTRUDA® for Advanced Bladder Cancer as the First and Only ADC Plus PD-1 Inhibitor Combination Therapy. Retrieved Dec 20, 2023, from https://mp.weixin.qq.com/s/VRDMDPu4bBSLfJQES18I1A