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Proposed MOA of
Enfortumab Vedotin (EV)
Actor portrayal.
Enfortumab vedotin is an investigational agent in some settings, and its safety and efficacy have not been established.
Enfortumab vedotin | An antibody-drug conjugate directed against Nectin-41,2
More to know
- EV is an antibody-drug conjugate (ADC) directed against Nectin-4 and is comprised of a fully human monoclonal antibody, the microtubule disrupting agent monomethyl auristatin E (MMAE), and a protease-cleavable linker. EV delivers MMAE to cells expressing Nectin-4, leading to cell cycle arrest and apoptotic cell death3
- Nectin-4 is a cell adhesion molecule that is expressed in both normal and tumor tissues. It is involved in multiple cellular processes known to be associated with oncogenesis, including cell adhesion, migration, proliferation, differentiation, and survival4,5
- High expression of Nectin-4 in select solid malignancies, including pancreatic, lung, breast, ovarian, and esophageal cancers, is associated with poor prognosis6-10
- The moderate to high expression levels of Nectin-4 in urothelial carcinoma (UC) and other tumors, compared with its low to moderate expression in normal tissues, make it a robust therapeutic target for drug development11
References: 1. PADCEV [package insert]. Northbrook, IL: Astellas Pharma US, Inc. 2. Liu BA, Olson D, Snead K, et al. Additional mechanisms of action of Enfortumab vedotin, an anti-Nectin-4 ADC demonstrating bystander effect and immunogenic cell death antitumor activity in models of urothelial carcinoma. Poster presented at: AACR Virtual Annual Meeting II; June 22-24, 2020. https://www.aacr.org/meeting/aacr-annual-meeting-2020/ 3. Rosenberg JE, O’Donnell PH, Balar AV, et al. Pivotal trial of enfortumab vedotin in urothelial carcinoma after platinum and anti-programmed death 1/programmed death ligand 1 therapy. J Clin Oncol 2019;37(29):2592-600. 4. Boylan KLM, Buchanan PC, Manion RD, et al. The expression of Nectin-4 on the surface of ovarian cells alters their ability to adhere, migrate, aggregate, and proliferate. Oncotarget 2017;8(6):9717-38. 5. Zhang Y, Liu S, Wang L, et al. A novel PI3K/AKT signaling axis mediates nectin-4-induced gallbladder cancer cell proliferation, metastasis and tumor growth. Cancer Lett 2016;375(1):179-89. 6. Deng H, Shi H, Chen L, Zhou Y, Jiang J. Over-expression of Nectin-4 promotes progression of esophageal cancer and correlates with poor prognosis of the patients. Cancer Cell Int 2019;19(106):1-13. 7. DeRycke MS, Pambuccian SE, Gilks B, et al. Nectin 4 overexpression in ovarian cancer tissues and serum: potential role as a serum biomarker. Am J Clin Pathol 2010;134(5):835-45. 8. Nishiwada S, Sho M, Yasuda S, et al. Nectin-4 expression contributes to tumor proliferation, angiogenesis and patient prognosis in human pancreatic cancer. J Exp Clin Cancer Res 2015;34(30):1-9. 9. Takano A, Ishikawa N, Nishino R, et al. Identification of nectin-4 oncoprotein as a diagnostic and therapeutic target for lung cancer. Cancer Res 2009;69(16):6694-703. 10. Zeindler J, Soysal SD, Piscuoglio S, et al. Nectin-4 expression is an independent prognostic biomarker and associated with better survival in triple-negative breast cancer. Front Med 2019;6(200):1-7. 11. Challita-Eid PM, Satpayev D, Yang P, et al. Enfortumab vedotin antibody-drug conjugate targeting nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer Res 2016;76(10):3003-13.
