CTNI-27. TRIAL IN PROGRESS A PHASE 2 STUDY OF BPM 31510 (AN OXIDIZED COQ10-LIPID CONJUGATE NANODISPERSION) WITH VITAMIN K AND STANDARD CHEMORADIATION IN NEWLY DIAGNOSED GLIOBLASTOMA

Abstract

Abstract INTRODUCTION: BPM 31510 is a novel drug-lipid conjugate nanodispersion that significantly increases the bioavailability of ubidecarenone (oxidized CoQ10). Supraphysiological concentrations of CoQ10 have been shown to have a paradoxical pro-oxidant effect on a variety of malignant cells while not altering the metabolic phenotype in normal cells. Glioblastoma multiforme (GBM) is a metabolically active cancer that is reliant on mechanisms of redox homeostasis to avert reactive oxygen species (ROS)-triggered apoptosis. This trial investigates whether this susceptibility of GBM metabolism may be effectively targeted by the potentially synergistic combination of BPM 31510 and standard-of-care radiotherapy, a known producer of ROS. Early-phase trials of BPM 31510 have shown a favorable safety profile with primarily hepatotoxicity and coagulopathy, the latter of which is mitigated by co-administration of Vitamin K. TRIAL DESIGN: BPM 31510IV-11 (NCT04752813) is a single-arm multicenter phase 2 study of BPM 31510 + Vitamin K1 in combination with standard chemoradiation for newly diagnosed GBM. Eligible patients have GBM with no prior therapy, and those with recent hemorrhage, coagulopathy, or who require anticoagulation are excluded. BPM 31510 starts 2-4 weeks after biopsy or resection initially as monotherapy for 2 weeks followed by an additional 6 weeks in combination with temozolomide-based chemoradiation. To assess safety of BPM 31510 with concomitant chemoradiotherapy, this study begins with a dose confirmation phase and allows for one dose reduction in the event of a DLT. The starting dose of BPM 31510 is 110 mg/kg administered as a continuous infusion over 96-hours weekly. The primary endpoint is 6-month progression-free survival (PFS6) by RANO criteria. Secondary endpoints include overall survival and safety. Approximately 50 patients will be enrolled for 90% power in rejecting the null hypothesis of PFS6 ≤ 30%. The study is enrolling at two US sites with a third opening soon.