Definition

An orally bioavailable, central nervous system (CNS) penetrating, mutant-selective covalent inhibitor of epidermal growth factor receptor (EGFR; ErbB1) and human epidermal growth factor receptor 2 (HER2; EGFR2; ErbB2) alterations, including exon 20 insertion (Ex20ins) mutations, with potential antineoplastic activity. Upon oral administration, EGFR/HER2 inhibitor ORIC-114 selectively targets, irreversibly binds to and inhibits the activity of EGFR or HER2 insertions or mutations. This prevents EGFR/HER2-mediated signaling. This may induce cell death and inhibit tumor growth in EGFR/HER2-overexpressing tumor cells. ORIC-114 is able to penetrate the blood-brain-barrier (BBB) and may therefore exert its activity against EGFR Ex20ins-driven CNS primary tumors and CNS metastases. The ErbB receptor tyrosine kinase family is involved in key cellular functions, including cell growth and survival. EGFR and HER2 alterations constitutively upregulate kinase activity.