Abstract 2968: BPM31510, a Coenzyme Q10 (CoQ10) containing lipid nanodispersion, enhances radiation effects to prolong survival in a rodent glioblastoma model

Abstract

Abstract BPM31510 is a Coenzyme Q10 (CoQ10)-containing lipid nanodispersion in clinical development for the treatment of glioblastoma. Prior results demonstrate that high doses of CoQ10 delivered via BPM31510 differentially increases oxidative stress in glioblastoma relative to non-tumor cells in vitro and extends long-term survival (LTS) in an in vivo glioblastoma model. Since a primary consequences of tumor irradiation is induction of oxidative stress, we hypothesized that BPM31510 treatment would result in an enhanced radiation response and influence survival outcomes.1 x 106 luciferase labeled C6 cells were implanted into the right striatum of Sprague Dawley rats. 4 days post-implantation, rats were randomized into one of four groups: (i) Saline injection ip bid; (ii) BPM31510 50 mg/kg ip bid to continue up to 35 days; (iii) 12 Gy radiotherapy (RT) to be administered on Day 8 post-implant with saline injection; and (iv) BPM31510 + RT. Tumor-bearing rats were monitored until death or Day 50. Log rank survival analysis indicated a marked enhancement of median survival with the addition of BPM31510 to RT. While neither RT nor BPM31510 enhanced median survival relative to saline, the combination was markedly more effective (median survival of 17, 19, 24 and >50 days for saline, BPM31510, RT and combination, respectively, p < 0.001). This was also reflected in increase in frequency of LTS, which was over 70% (11 of 14 rats) in the combination group (p < 0.01 compared to control). BPM31510 significantly enhanced the therapeutic efficacy of radiation in this model of glioblastoma. Effects on median survival and an enhancement of LTS with combination treatment were observed. While the mechanistic underpinnings are under investigation, the low toxicity profile of BPM31510 and its potential protective effects on normal cells may offer a unique strategy with which to enhance radiation. Citation Format: Jiaxin Sun, Milton Merchant, Anne R. Diers, Shiva Kazerounian, Stephane Gesta, Niven R. Narain, Rangaprasad Sarangarajan, Seema Nagpal, Lawrence Recht. BPM31510, a Coenzyme Q10 (CoQ10) containing lipid nanodispersion, enhances radiation effects to prolong survival in a rodent glioblastoma model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2968.