499TiP - A phase II study of BPM31510 (a lipid nanodispersion of oxidized CoQ10) with vitamin K in combination with standard of care (SOC) RT and TMZ in glioblastoma multiforme (GBM) patients without prior therapy

Background

BPM31510 is a novel drug-lipid conjugate nanodispersion that has been shown to result in 10,000X supraphysiological levels of oxidized CoQ10. Preclinical studies show that supraphysiological concentrations of oxidized CoQ10 induce a metabolic shift in cancer cells while sparing normal cells. This metabolic shift is accompanied by Reactive Oxygen Species (ROS) generation leading to apoptosis. Main AEs in phase I were hepatotoxicity and coagulopathy. DLT was not achieved even at the highest dose level. Coagulopathy (prolonged PT/INR, PTT/aPTT) was alleviated by prophylactic administration of Vitamin K. Starting at phase I, RP2D dose has remained at 110 mg/kg/week.

Trial design

BPM31510IV-11 (NCT04752813) is a single-arm, non-randomized, open-label, phase II study of BPM31510 + Vitamin K1 with standard chemoradiation and TMZ in newly diagnosed GBM patients. The primary endpoint is progression-free survival at 6 months (PFS6) while the secondary endpoints are overall survival, PFS12, and safety. Patients with recent hemorrhage, coagulopathy, or requiring anticoagulants are excluded. Weekly intravenous BPM31510 is initiated 2-4 weeks after biopsy or tumor resection. After two weekly BPM31510 doses, standard chemoradiation and TMZ protocols are implemented in combination with BPM31510 for 6 weeks. Treatment concludes after 8 weeks of BPM31510 treatment to coincide with end of standard RT schedule. Subjects can receive maintenance TMZ treatment for up to 12 cycles. BPM31510 started at 110mg/kg body weight and one dose reduction was permitted in the event of a DLT. The Data and Safety Monitoring Committee approved the 110 mg/kg dose level and trial continuation. The BPM31510IV-11 trial will enroll approximately 50 patients for ∼90% power in rejecting the null hypothesis of PFS6 of ≤ 30%. The study is currently open at 4 US sites, with additional sites opening in the upcoming months. BPM31510IV-11 has enrolled thirteen (13) patients and to date seven (7) patients have completed the study.

Clinical trial identification

NCT04752813.

Editorial acknowledgement

Legal entity responsible for the study

BPGbio, Inc.

Funding

BPGbio, Inc.

Disclosure

A. Lyng, B. Berman, V.K. Vishnudas, M.A. Kiebish, S. Gesta, P.K. Tekumalla, V. Modur: Financial Interests, Personal, Full or part-time Employment: BPGbio. N.R. Narain: Financial Interests, Personal, Full or part-time Employment: BPGbio; Financial Interests, Personal, Stocks/Shares: BPGbio. All other authors have declared no conflicts of interest.