ACTR-30. EORTC 1608: A PHASE 1B STUDY OF TG02, AN ORAL CYCLIN-DEPENDENT KINASE 9/5 INHIBITOR, IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA STRATIFIED BY MGMT PROMOTER METHYLATION STATUS

Abstract

BACKGROUND: TG02 is an orally bioavailable, multi-kinase inhibitor which appears to exert anti-tumor activity mainly by inhibiting cyclindependent kinase (CDK) 9, resulting in the depletion of oncoproteins such as induced myeloid leukemia cell differentiation protein (MCL) 1 and MYC (Myelocytomatosis-associated). TG02 exhibits strong activity in glioma models including stem cell models at concentrations likely to be achieved in human patients in vivo and shows promising blood brain barrier penetration. METHODS: Based on the strong preclinical data for TG02, the EORTC Brain Tumor Group has initiated EORTC 1608 study, a phase 1b dose-escalation and safety study of TG02 in combination with either hypofractionated radiotherapy (cohort A) or temozolomide (cohort B) in elderly patients with newly diagnosed glioblastoma not considered eligible for combined modality treatment. Patient allocation to treatment will be determined by O6-methylguaine DNA methyltransferase (MGMT) promoter methylation status according to European Association of Neuro-Oncology (EANO) guidelines for elderly patients with glioblastoma: unmethylated (cohort A) versus methylated (cohort B). Further, we will explore single agent activity of TG02 in glioblastoma patients aged 18 or more at first progression after temozolomide chemoradiotherapy with progression-free survival at 6 months as the main efficacy endpoint (cohort C). RESULTS: We will report on the current preclinical stage of development of TG02 and update on the clinical trial conducted by the EORTC Brain Tumor Group. CONCLUSION: TG02 targets a novel oncogenic pathway activated in glioblastoma, warranting studies on its activity in early clinical trials.