Cixutumumab, or IMC-A12 is a monoclonal antibody against IGF1-R.
Manufacturer: ImClone, website link www.ImClone.com
oral or intravenous: intravenous
Definition from NCI Drug Dictionary: Cixutumumab is a fully human IgG1 monoclonal antibody directed against the human insulin-like growth factor-1 receptor (IGF-1R) with potential antineoplastic activity. Cixutumumab selectively binds to membrane-bound IGF-1R, thereby preventing the binding of the natural ligand IGF-1 and the subsequent activation of PI3K/AKT signaling pathway. Downregulation of the PI3K/AKT survival pathway may result in the induction of cancer cell apoptosis and may decrease cancer cellular proliferation. IGF-1R, a receptor tyrosine kinase of the insulin receptor superfamily overexpressed by many cancer cell types, stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis; IGF-1R signaling has been implicated in tumorigenesis and metastasis.
Development: Evidence from preclinical studies show that Cixutumumab (IMC-A12) effectively blocked IGF-1R and inhibited ligand-dependent signaling and tumor growth in models of human breast cancer, colon and pancreatic cancer. In September 2007, NCI selected 10 proposals for Phase 1 and 2 clinical trials of IMC-A12 exploring the clinical activity, pharmacology and biological effects of the drug as a single agent and in combination with other anti-cancer agents in a wide range of malignancies, including both adult and pediatric sarcomas. Several other proposals have been selected since that time.
Clinical trials with that have relevance to GIST include:
Multi-center Phase 1 trial of IMC-A12 in Children with Relapsed/Refractory Solid Tumors (NCT00609141) This trial has been completed.