ACTR-53. STEAM / EORTC 1608: STUDY OF TG02 IN ELDERLY NEWLY DIAGNOSED OR ADULT RELAPSED PATIENTS WITH ANAPLASTIC ASTROCYTOMA OR GLIOBLASTOMA - A PHASE 1B STUDY

摘要

BACKGROUNDTG02 is an oral multi-cyclin dependent kinase (CDK) inhibitor that is thought to inhibit tumor growth mainly through CDK9-dependent depletion of oncoproteins such as MCL-1 and MYC. MCL-1 and MYC are frequently overexpressed in glioblastoma (up to 80%). Several studies including analyses of patient-derived glioma cell lines have demonstrated profound inhibitory activity (IC50 range = 25–150 nM). Clinical pharmacokinetics from a phase 1b study in multiple myeloma patients demonstrate that TG02 exposures in humans are sufficient for achieving inhibitory concentrations required in the majority of the glioma cell lines tested. Preclinical studies in mice have demonstrated that TG02 is a good candidate for development in gliomas.