Initial Testing (Stage 1) of LCL161 a SMAC Mimetic by the Pediatric Preclinical Testing Program

摘要

LCL161, a SMAC mimetic, was tested against the PPTP in vitro panel (1.0 nM to 10.0 μM) and the PPTP in vivo panels (30 mg/kg or 75 mg/kg [solid tumors] or 100 mg/kg [ALL]) administered orally twice weekly. LCL161 showed a median relative IC50 value of >10 μM, being more potent against several leukemia and lymphoma lines. In vivo LCL161 induced significant differences in EFS distribution in approximately one-third of solid tumor xenografts (osteosarcoma, glioblastoma), but in no ALL xenografts. No objective tumor responses were observed. In vivo LCL161 demonstrated limited single agent activity against the pediatric preclinical models studied.