Enapotamab vedotin (HuMax-AXL-ADC)

Enapotamab vedotin (HuMax®-AXL-ADC) is an antibody-drug conjugate (ADC) targeted to Axl (from anexelekto, or uncontrolled growth). Axl is a unique RTK that is aberrantly expressed in many solid tumor types and is implicated in tumor cell proliferation, migration, and invasion.1 Enapotamab vedotin is in Phase I/II development for multiple types of solid tumors: ovarian, cervical, endometrial, thyroid, non-small cell lung cancer, melanoma and sarcoma.2 Enapotamab vedotin is fully owned by Genmab, and the ADC technology used with enapotamab vedotin has been licensed from Seattle Genetics

Axl was first described as a transforming gene in chronic myeloid leukemia.1 It is a receptor tyrosine kinase (RTK) that belongs to the TAM (Tyro3, Axl, and Mer) family.3

Axl function in normal physiology includes:
• Tissue homeostasis4
• Regulation of inflammation and autoimmune responses3
• Sperm production5

Axl contributes to tumor progression and has been associated with poor clinical prognosis in many cancer types.3 Overexpression has been described in solid cancers, including lung, esophageal, ovarian, breast, cervical, thyroid, endometrial, pancreatic, and others.1,2

Axl is emerging as a marker in tumors with resistance to therapy (tyrosine kinase inhibitors, chemotherapy).1,3 In addition, overexpression of Axl is observed in advanced tumors with epithelial–mesenchymal transition (EMT)-like features.1

 
References
1 Song X, Wang H, Logsdon CD, et al. Overexpression of receptor tyrosine kinase Axl promotes tumor cell invasion and survival in pancreatic ductal adenocarcinoma. Cancer. 2011;117(4):734-743.
2 US National Institutes of Health. HuMax-AXL-ADC safety study in patients with solid tumors. https://clinicaltrials.gov/ct2/show/NCT02988817?term=genmab+axl&rank=1. Updated August 16, 2017. Accessed March 14, 2018. 
3 Linger RMA, Keating AK, Earp HS, Graham DK. TAM receptor tyrosine kinases: biologic functions, signaling, and potential therapeutic targeting in human cancer. Adv Cancer Res. 2008;100:35-83.
4 Holland SJ, Powell MJ, Franci CF, et al. Multiple roles for the receptor tyrosine kinase Axl in tumor formation. Cancer Res. 2005;65(20):9294-9303.
5 Lu Q, Gore M, Zhang Q, et al. Tyro-3 family receptors are essential regulators of mammalian spermatogenesis. Nature. 1999;398(6729):723-728.

 


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Enapotamab vedotin is being tested in multiple solid tumors (ovarian, cervical, endometrial, thyroid, non-small cell lung cancer, melanoma and sarcoma). For more information on studies of enapotabmab vedotin, visit clinicaltrials.gov

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