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

Abstract

BACKGROUND: TG02 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. METHOD(S): Based on these data, the EORTC Brain Tumor Group, in cooperation with Tragara, is currently conducting the phase 1b STEAM trial (EORTC 1608), a three parallel group (A,B,C) open‐label, non‐randomized, multicenter study. The recommended phase II dose of TG02 in elderly patients with IDH1R132H‐non mutant newly diagnosed glioblastoma will be determined in a classical 3 + 3 design dose‐escalation and safety study of TG02 in combination with either hypofractionated radiotherapy (RT) or temozolomide (TMZ) in arms A and B. Patient allocation to treatment in arms A and B will be determined by MGMT promoter methylation status centrally determined according to EANO guidelines for the treatment of elderly patients with glioblastoma. Arm C will explore single agent TG02 activity in anaplastic astrocytoma or glioblastoma at first relapse after initial treatment with TMZ/RTTMZ with a primary endpoint of progression‐free survival at 6 months. Secondary objectives include efficacy, quality of life, safety, and correlation with molecular markers. The study is currently open in 2 sites and shall be opened until SNO in 5 additional EORTC sites in Europe. Patient enrolment is planned to start in June 2018. An update will be provided at the SNO conference.