ACTR-71. PHASE 1/2 STUDY OF DIANHYDROGALACTITOL (VAL-083) WITH RADIATION THERAPY IN PATIENTS WITH NEWLY DIAGNOSED, MGMT-UNMETHYLATED GLIOBLASTOMA

ABSTRACT: Abstract Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Current standard-of-care includes surgery followed by chemo-radiation and temozolomide. An unmethylated promoter for O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for temozolomide-resistance and is strongly correlated with poor outcomes. Unmethylated MGMT represents the majority of newly diagnosed GBM tumors. VAL-083 is a first-in-class bi-functional DNA-targeting agent that has shown activity against GBM in NCI-sponsored clinical trials both as single agent and in combination with radiotherapy. VAL-083 induces interstrand cross-links at N7-guanine, leading to DNA double-strand breaks and cell-death. VAL-083s unique mechanism-of-action circumvents MGMT-mediated chemoresistance, and

SUBMITTER: Chen Z 

PROVIDER: S-EPMC6216509 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature