The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Enfortumab vedotin

Geo Regions

Enfortumab vedotin

Overview + Rationale

  • Enfortumab vedotin (EV) is an antibody-drug conjugate directed to Nectin-4. It is made up of a fully human monoclonal antibody specific for Nectin-4, the microtubule disrupting agent monomethyl auristatin E (MMAE), and a protease-cleavable linker maleimidocaproyl-valine-citrulline that covalently attaches MMAE to the antibody which may enable preferential release of MMAE within target cells.1,2 Delivery of intracellular MMAE to tumor cells expressing Nectin-4 leads to cell cycle arrest and apoptotic cell death3 
  • Nectin-4 is a cell adhesion molecule that is expressed in both normal and tumor tissues and is involved in multiple cellular processes known to be associated with oncogenesis, including cell adhesion, migration, proliferation, differentiation, and survival4 
  • High expression of Nectin-4 in select solid malignancies, including pancreatic, lung, breast, ovarian, and esophageal cancers, is associated with poor prognosis5-11 

  • The elevated expression levels of Nectin-4 in urothelial carcinoma and other tumors, compared to its low-to-moderate expression in normal tissues, make it a robust therapeutic target for drug development4,5 

    Partner: Astellas Pharma Global Development, Inc.

Stage of Development

Enfortumab vedotin is being investigated in the tumor types shown below. Safety and efficacy for the uses listed below have not been established.

Small icon representing GU Cancer
Locally Advanced or Metastatic Urothelial Cancer
Phase 1 Mono and Combo*§

Phase 2 Mono and Combo*†

Phase 3 Combination
Small icon representing GU Cancer
Cisplatin-Eligible Muscle-Invasive Bladder Cancer
Phase 3 Combination*§
Small icon representing Early Solid Tumors
Locally Advanced or Metastatic Solid Tumors
Phase 2 Monotherapy and Combination
Small icon representing GU Cancer
BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer
Phase 1 Monotherapy
Small icon representing GU Cancer
Cisplatin-Ineligible/decline cisplatin muscle-invasive bladder cancer
Phase 3 Combination§

*Closed to Enrollment. § Study sponsored by Merck Sharp and Dohme LLC. † Study sponsored by Astellas Pharma Global Development, Inc.

REFERENCES: 1. Senter PD. Curr Opin Chem Biol. 2009;13:235-44; 2. Doronina SO. Nat Biotechnol. 2003;21(7):778-84; 3. Rosenberg JE. J Clin Oncol. 2019;37(29):2592-600; 4. Boylan KLM. Oncotarget. 2017: 9717-38; 5. Challita-Eid PM. Cancer Res. 2016: 3003-13; 6. Zhang Y. Cancer Lett. 2016: 179-89; 7. Deng H. Cancer Cell Int. 2019;19(106):1-13.; 8. DeRycke MS. Am J Clin Pathol 2010;134(5):835-45; 9. Nishiwada S. J Exp Clin Cancer Res 2015;34(30):1-9; 10. Takano A. Cancer Res 2009;69(16):6694-703; 11. Zeindler J. Front Med 2019;6(200):1-7. 12. NCT05562830. https://clinicaltrials.gov/study/NCT05562830 Accessed February 25, 2024; 13. NCT03288545. https://clinicaltrials.gov/study/NCT03288545; Accessed February 25, 2024; 14. NCT04223856 https://clinicaltrials.gov/study/NCT04223856 Accessed February 25, 2024: 15. NCT05014139 https://clinicaltrials.gov/study/NCT05014139 Accessed February 25, 2024; 16. NCT04700124 https://clinicaltrials.gov/study/NCT04700124; Accessed February 25, 2024; 17. NCT03924895 https://clinicaltrials.gov/study/NCT03924895 Accessed February 25, 2024; 18. NCT04225117 https://clinicaltrials.gov/study/NCT04225117; Accessed February 25, 2024: