Phase 1a/b Multi-Center Study of BPM31510IV Targeting Mitochondrial Metabolism/Warburg Effect as Monotherapy and Combination Chemotherapy in Solid Tumor Patients.
Academic Article
Overview
abstract
PURPOSE: BPM31510IV, a highly bioavailable intravenously administered coenzyme Q10 (CoQ10) formulation evaluated in a Phase 1a/1b study as monotherapy and in combination with chemotherapy in patients with advanced solid tumors. PATIENTS AND METHODS: Using a 3+3 design, patients received twice-weekly intravenous infusions of BPM31510IV monotherapy (Arm 1) or combined with gemcitabine, 5-fluorouracil/leucovorin, or docetaxel (Arm 2); crossover between arms was permitted. Tumor response was assessed by RECIST1.1. Pharmacokinetic and multi-omics pharmacodynamic (PD) analyses were performed on plasma and core biopsy samples. RESULTS: 97 patients were enrolled, 33 in Arm 1 and 71 in Arm 2 (seven patients crossed from Arm 1 to Arm 2). The maximum-tolerated dose was 171 mg/kg for BPM31510IV monotherapy or with 5-fluorouracil/leucovorin and 110 mg/kg with gemcitabine or docetaxel. Four dose-limiting toxicities occurred (two in monotherapy; two in combination with chemotherapy). Most adverse events were coagulation-related, occurring in 96% of patients (Grade ≥3 in 4%). Pharmacokinetics showed dose-proportional increases in CoQ10 levels to supraphysiologic concentrations (>200×). In Arm 1, there was one (3%) partial response (PR), with stable disease (SD) reported in 8 (24%) patients. In Arm 2, there was one (1%) PR with SD reported in 25 (35%) patients. Fluorodeoxyglucose-positron emission tomography imaging and PD data suggest a change in tumor metabolism from glycolysis to oxidative phosphorylation. CONCLUSIONS: BPM31510IV monotherapy and in combination with chemotherapy was safe, with preliminary evidence of anti-tumor activity. High plasma CoQ10 levels were achieved, inducing PD responses consistent with mitochondrial metabolic changes. These findings support continued clinical development of BPM31510IV.
