Drug intelligence / Profile preview

lenalidomide + sunitinib + cyclophosphamide

Development stage
Phase 2
Lead developer
NIH Clinical Center
Modality
Small Molecules
Administration
Oral
01

Overview

This combination therapy consists of the immunomodulatory drug lenalidomide, the multi-kinase inhibitor sunitinib malate, and low-dose metronomic cyclophosphamide. It was evaluated in a Phase II clinical trial (NCT00482911) led by the National Institutes of Health Clinical Center (CC) for the treatment of stage IV ocular (uveal) melanoma. Lenalidomide is an immunomodulatory imide drug (IMiD) that targets the cereblon E3 ubiquitin ligase complex, leading to anti-angiogenic and pro-apoptotic effects. Sunitinib is a multi-targeted receptor tyrosine kinase inhibitor that primarily inhibits vascular endothelial growth factor receptors (VEGFR) and platelet-derived growth factor receptors (PDGFR), which are critical for tumor angiogenesis. Cyclophosphamide is an alkylating chemotherapy agent administered at low, metronomic doses to exert anti-angiogenic effects and modulate the tumor microenvironment by reducing regulatory T-cell activity. The combination was designed to synergistically inhibit tumor growth and angiogenesis in metastatic ocular melanoma.

Other names
Lenalidomide, Sunitinib, and Cyclophosphamide for Stage IV Ocular Melanoma
02

Targets

CRBN (Cereblon)CSF1R (Macrophage colony-stimulating factor receptor)DNAFLT3 (Fms related receptor tyrosine kinase 3)KIT (c-KIT proto-oncogene receptor tyrosine kinase)PDGFRA (Platelet-derived growth factor receptor alpha)PDGFRB (Platelet-derived growth factor receptor beta)RET (Rearranged during transfection receptor tyrosine kinase)VEGFR-1 (Vascular endothelial growth factor receptor 1)VEGFR2 (Vascular endothelial growth factor receptor 2)VEGFR4 (Vascular endothelial growth factor Receptor-3)

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