▎WuXi AppTec Content Team Report

Bladder cancer is a common tumor of the urinary system. Urothelial carcinoma is the most common type of bladder cancer, accounting for about 90% of bladder cancer cases. Urothelial carcinoma is a highly malignant tumor. Platinum-based regimens are effective first-line treatments for patients with advanced stages, but after a period of time, patients tend to develop resistance to chemotherapy, leading to tumor recurrence and progression. Moreover, treatment options are limited for patients after the failure of platinum-based chemotherapy.

Nectin-4 is a protein located on the cell surface and highly expressed in bladder cancer. Studies have shown that the anticancer activity of intravenous Vedotin Monomethyl Auristatin E (MMAE) is due to its binding to cells expressing the Nectin-4 protein, followed by the internalization and release of the antitumor component MMAE into the cells, leading to...Leading to cell cycle arrest and programmed cell death (apoptosis).

According toAccording to a previous press release from Astellas,The marketing application approval of Vedotin is based onEV-203 Study Data, this is a single-arm, open-label, multi-center phase 2 clinical trial designed to evaluateVientamabTreatment of locally advanced or metastatic urothelial carcinoma previously treated with PD-1/PD-L1 inhibitors and platinum-containing chemotherapyChinese PatientsEfficacy, safety, and pharmacokinetic characteristics.The study enrolled a total of 40 patients.

According to Astellas at the 2023 American Society of Clinical Oncology (ASCO) Annual MeetingResearch DataPatients receiving monotherapy with intravenous Vientoyuzumab,The Objective Response Rate (ORR) assessed by the Independent Review Committee (IRC) was 37.5%, and the Disease Control Rate (DCR) was 72.5%., with its efficacy data and PK data consistent with the global data. In terms of secondary endpoints, the candidate drug also demonstrated clinically meaningful improvements in efficacy.The ORR assessed by the investigator was 42.5%, and the DCR was 82.5%.；The median progression-free survival (PFS) assessed by the Independent Review Committee was 4.67 months.。

It is worth mentioning that in December 2023, the U.S. FDA announcedFull ApprovalVientoyumabIn combination with MSD's PD-1 inhibitor pembrolizumab, used forFirst-line treatmentAdult patients with locally advanced or metastatic urothelial carcinoma. In China, the first-line treatment indication for this combination therapy was accepted by the NMPA in March 2024. Astellas previously stated in a press release that if approved,The Combination TherapyWill replace the current first-line standard chemotherapy for locally advanced or metastatic urothelial carcinoma, becoming the first combination therapy in China to replace chemotherapy.

References:

[1] Drug Approval Certificate Delivery Information on August 19, 2024. Retrieved Aug 19, 2024, from https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20240819150923195.html

[2] China's National Medical Products Administration Accepts the Biologics License Application for Enfortumab Vedotin to Treat Patients with Locally Advanced or Metastatic Urothelial Cancer. Retrieved Mar 9, 2023, from https://mp.weixin.qq.com/s/eqIpC765Nrpt2r4q5RSlvQ

[3] Astellas Announces Positive Results from EV China Bridging Study at the 2023 ASCO Annual Meeting. Retrieved Jun 2, 2023, from https://www.prnasia.com/story/406479-1.shtml

[4] Astellas 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