Compound DescriptionOral, selective c-Met RTK inhibitor
Areas of ResearchSolid tumors
Proposed Mechanism of ActionINC280 is a highly selective inhibitor of c-MET. In human malignant disease, the c-Met pathway is one of the dysregulated pathways.1 Inappropriate signaling through the c-Met RTK occurs in multiple types of human cancers due to receptor overexpression, gene amplification, gene mutation and/or ligand-dependent activation, and contributes to malignant progression through increased cell proliferation, survival, invasion, and metastasis.1–3 Aberrant c-Met signaling has been documented in many tumor types, including most carcinomas.1–3
Key Preclinical DataINC280 has demonstrated inhibitory activity (IC50 values: 0.2–2 nM) in cell-based biochemical and functional assays that measure c-Met signaling and c-Met–dependent cell proliferation, survival, and migration.3,4 Oral administration of INC280 conferred in vivo activity in blocking both c-Met phosphorylation and tumor growth in mouse tumor models.3,4 Furthermore, INC280 is highly specific for c-Met kinase inhibition.3,5 It has demonstrated > 10,000-fold selectivity to c-Met over a panel of more than 50 human kinases in in vitro assays.3,5
Clinical StatusThere are several ongoing trials of INC280 in various solid tumors. A Phase I, open-label, dose-escalation with expansion to assess the safety and efficacy of INC280 in patients with solid tumors that are refractory to current treatment or for which there is not a current standard of care and whose tumors have dysregulation of the c-MET pathway.
A Phase Ib/II study is assessing the safety and efficacy of escalating doses of INC280 when added to gefitinib in patients with lung cancer that are known to have dysregulation of the c-MET pathway and who have failed after benefiting on a prior treatment with either gefitinib or erlotinib.7 A Phase II study is currently evaluating the safety and efficacy of INC280 in patients with advanced hepatocellular carcinoma known to have dysregulation of the c-MET pathway.8
The information contained herein was last updated on April 12, 2013.
All Compounds are either investigational or studied in new indications. Efficacy and safety have not been established. There is no guarantee that they will become commercially available.
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