LOXO-292 demonstrated potent and selective anti-RET activity preclinically against human cancer cell lines harboring endogenous RET gene alterations; cells engineered to express a KIF5B-RET fusion protein -/+ the RET V804M gatekeeper resistance mutation or the common RET activating mutation M918T; and RET-altered human cancer cell line and patient-derived xenografts, including a patient-derived RET fusion-positive xenograft injected orthotopically into the brain.
Comprehensive genomic profiling performed by means of a clinical grade cancer gene panel next-generation sequencing assay demonstrated a KIF5B-RET fusion in three; and fluorescence in-situ hybridization documented a RET rearrangement in two.