MA13.05 TA0953/HM06, a Novel RET-specific Inhibitor Effective in Extracranial and CNS Disease Models of NSCLC with RETfusions

RET kinase fusions act as oncogenic drivers in approximately 2% of NSCLC patients. Two RET-selective kinase inhibitors, selpercatinib and pralsetinib, have proven effective at reducing tumor burden, and are FDA-approved. However, the emergence of resistance to these drugs, and brain metastasis, remain serious clinical challenges. TAS0953/HM06 is a new pharmacologically advanced RET-specific inhibitor that is structurally different from other RET inhibitors, has superior brain penetration kinetics compared to selpercatinib and pralsetinib, and retains activity in the setting of RET G810 (solvent front) mutations.