Data from Phase Ia/b Multicenter Study of BPM31510IV Targeting Mitochondrial Metabolism/Warburg Effect as Monotherapy and Combination Chemotherapy in Solid Tumor Patients

作者：Vivek Subbiah, Peter Paul Yu, Rangaprasad Sarangarajan, Michael A. Kiebish, Leonardo O. Rodrigues, Gregory M. Miller, Viatcheslav R. Akmaev, Shen Luan, John P. McCook, Nikunj Tanna, Tracey Reilly, Emily Chen, Valerie Bussberg, Shobha Ravipaty, Vivek K. Vishnudas, Stéphane Gesta, David Lucius, Can Bruce, Suwagmani Hazarika, Arianne Lyng, Allison Klotz, Vladimir Tolstikov, Janice R. Stevens, Victoria S. Chua, Elder Granger, Poornima K. Tekumalla, Ely Benaim, Vijay Modur, Marc S. Rudoltz, Paul Y. Song, Scott T. Tagawa, Andrew Hendifer, Sant P. Chawla, Manish A. Shah, David S. Hong, Ralph Zinner, Niven R. Narain, Madappa N. Kundranda · 年份：2025 · DOI：10.1158/2767-9764.c.8216454 · 研究领域：Coenzyme Q10 studies and effects、Mitochondrial Function and Pathology、ATP Synthase and ATPases Research

<div>AbstractPurpose:BPM31510IV, a highly bioavailable intravenously administered coenzyme Q10 (CoQ10) formulation, was evaluated in a phase Ia/Ib 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 multiomics pharmacodynamic (PD) analyses were performed on plasma and core biopsy samples.Results:A total of 97 patients were enrolled, 33 in arm 1 and 71 in arm 2 (seven patients crossed from arm 1 to arm 2). The MTD 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 eight (24%) patients. In arm 2, there was one (1%) PR, with SD reported in 25 (35%) patient...