▎Edited by the WuXi AppTec content team

Today (March 28), the official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China showed,Astellas (Astellass) Submitted byInjectable VientoyouMonoclonal antibodies and MSD submittedPembrolizumabThe listing application has been accepted.Vientamab is aTargetedAntibody-drug conjugates targeting Nectin-4 (ADC），Co-developed by Astellas and Seagen (acquired by Pfizer), pembrolizumab is a product developed by MSD.Anti-PD-1 MonoclonalAnti. According toAstellas News Release, the current submission isVientoyouMonoclonal AntibodyIn combination with pembrolizumabSupplemental Biologics License Application (sBLA), intended for first-line treatment of previously untreated locally advanced or metastaticAdult patients with urothelial carcinoma。

Screenshot source: CDE official website

Urothelial carcinoma (UC) includes cancers of the lower urinary tract (bladder and urethra) and upper urinary tract (ureter and renal pelvis), with lower urinary tract cancers accounting for 90% to 95% of all urothelial carcinoma cases. It is estimated that in 2022, approximately 93,000 patients in China were diagnosed with bladder cancer, and about 41,000 patients died.[3]。 

Vedotin is an antibody-drug conjugate that directly targets Nectin-4.Nectin-4 isA protein located on the cell surface that is highly expressed in bladder cancer.Vientoyumab canBinding to cells expressing the Nectin-4 protein, it then internalizes and releases the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, causing cell cycle arrest and programmed cell death (apoptosis). In March 2023,CDE has alreadyAcceptanceNivolumab for the treatment of locally advanced or metastatic urothelial carcinoma patients who have previously received PD-1/L1 and platinum-based chemotherapy.

Previously, Astellas and Pfizer entered into a clinical collaboration agreement with MSD to evaluate the efficacy of Astellas and Pfizer’s enfortumab vedotin in combination with MSD’s pembrolizumab (Keytruda) for the treatment of patients with previously untreated metastatic urothelial cancer.The U.S. FDA approved in December 2023Vientamab and PembrolizumabCombination Therapy。

According to the introduction in Astellas' press release, thisVientamabThe sBLA for the combination therapy used in first-line treatment is based on aPhase 3 Clinical Trial EV-302(Also known as KEYNOTE-A39) The results showed 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 statistically significant and clinically meaningful outcomes.

• The median overall survival for the combination therapy was 31.5 months (vs 16.1 months for the chemotherapy group), meaning that compared to the chemotherapy group,The risk of death was reduced by 53% in patients receiving combination therapy.

• The median progression-free survival in the combination therapy group was 12.5 months (vs 6.3 months in the chemotherapy group), meaning that compared with the chemotherapy group,Patients in the combination therapy group had a 55% reduction in the risk of cancer progression or death.

• Consistent overall survival and progression-free survival results were observed in the predefined subgroups, including cisplatin tolerance and PD-L1 expression levels. In the cisplatin-tolerant subgroup and the cisplatin-intolerant subgroup (with 244 and 198 patients, respectively), the risk of death was reduced by47%And57%, the risk of disease progression or death was reduced by52%And57%. The risk of death was reduced in the PD-L1 low-expression subgroup and PD-L1 high-expression subgroup (184 and 254 people, respectively).56%And51%, the risk of disease progression or death was reduced by50%And58%。

Principal Investigator of EV-302 Trial in China, Director of the Department of Melanoma and Genitourinary Tumor Medicine at Peking University Cancer HospitalProfessor Guo JunIt is reported that the current first-line treatment strategy for advanced urothelial carcinoma in China remains 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 still need further improvement. Therefore, there is an urgent clinical need for the emergence of a breakthrough first-line treatment to further improve patient outcomes. The global data from the EV-302 study has established...MaintenanceEntuximabIn combination with pembrolizumab as a first-line regimen without platinum-based chemotherapy. Compared with chemotherapy, this treatment regimen can achieve a clinically meaningful improvement in efficacy., nearly doubling the median progression-free survival and significantly extending the survival period of patients with advanced urothelial carcinoma.。

Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, GuangzhouProfessor Huang JianThe global research data of EV-302 confirmed that in the population of patients with advanced urothelial carcinoma,MaintenanceEntocortIn combination with pembrolizumabCompared with the significant efficacy and safety of chemotherapy, the combination therapy that has emerged in the past 20 to 30 years is superior to platinum-based chemotherapy and is expected to become the new first-line standard treatment for advanced urothelial carcinoma. It is hoped that it will be approved by regulatory authorities in China as soon as possible to benefit more Chinese patients.

[1] 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