Progress report of a phase 2 study of BPM31510 (a lipid nano dispersion of oxidized CoQ10) with vitamin K in combination with standard of care (SOC) RT and TMZ in glioblastoma multiforme (GBM) patients without prior therapy.

Abstract

TPS2101 Background: BPM31510 is an investigational, drug-lipid conjugate nanodispersion. Preclinical studies demonstrate that intravenous infusion can achieve plasma concentrations of oxidized CoQ10 approximately 10,000 times higher than baseline physiological levels with its accumulation in organs, including brain. Preclinical studies show that supraphysiological concentrations of CoQ10 induce metabolic shifts in a variety of cancer cells and generate Reactive Oxygen Species (ROS) leading to apoptosis. In Phase 1, the main adverse events were related to mild hepatotoxicity and coagulopathy. All coagulation related issues were alleviated by coadministration of Vitamin K. The Phase 2 trial in newly diagnosed patients with glioblastoma tests whether treatment with BPM31510 results in improved efficacy of standard of care temozolomide (TMZ) and radiotherapy (RT). Methods: BPM31510IV-11; NCT04752813 is a single-arm, non-randomized, open-label, phase 2 study of intravenous (IV) BPM31510 + prophylactic subcutaneous (SC) Vitamin K1 with standard chemoradiation and temozolomide (TMZ) in newly diagnosed GBM patients. The primary endpoint is Progression Free Survival at 6 months (PFS6) and 12 months (PFS12) while the secondary endpoints are Overall S (OS) survival and safety. Patients with recent hemorrhage, coagulopathy, or requiring anticoagulants are excluded. SC Vit K and IV BPM31510 are initiated 2-4 weeks after biopsy or tumor resection. After two weeks, standard of care chemoradiation and TMZ are started in combination with weekly IV BPM31510 for 8 weeks, after which IV BPM31510 treatment and standard RT are discontinued with subjects continuing to receive maintenance TMZ treatment for up to 12 cycles as per standard of care. Of the approximately 50 patients enrolled and treated upon the recommendation of an independent safety monitoring committee, 25 will be available for PFS6 efficacy endpoint analysis and these data will be presented. Clinical trial information: NCT04752813 .