BPM31510, an investigational mitochondrial-targeted therapy, given in combination with standard-of-care (SOC) radiation and temozolomide (Temodar), produced an encouraging overall survival (OS) trend in patients with newly diagnosed glioblastoma (GBM), according to preliminary findings from an ongoing phase 2 trial (NCT04752813).1,2
Patients in the overall population evaluable per protocol (n = 39) experienced a median OS of 19.3 months (95% CI, 15.0-not reached [NR]).1,2 Notably, patients with MGMT-unmethylated tumors (n = 24) achieved a median OS of 29.3 months (95% CI, 12.8-NR), compared with a historical control range of 12.7 to 15.5 months.1,2 Median OS was NR (95% CI, 10.6-NR) in the 13 evaluable patients with MGMT-methylated tumors.2
“As the data continue to mature, we are increasingly encouraged by the preliminary findings emerging from both cohorts, particularly the OS trends observed in the cohort with MGMT-unmethylated GBM,” Niven R. Narain, PhD, president and chief executive officer of BPGbio, stated in the news release.1
BPM31510 is a lipid nanodispersion of oxidized coenzyme Q10 (CoQ10) administered with vitamin K1.1 The agent is designed to target the tumor microenvironment and alter the mitochondrial metabolic machinery to modulate oxidative phosphorylation reactivation and reactive oxygen species production, thereby restoring apoptotic function in tumors. In cancer, altered mitochondrial metabolism supports tumor growth, therapeutic resistance, and adaptation to oxidative stress. BPM31510 was designed to address these metabolic vulnerabilities while supporting efficient metabolism in nontumorigenic tissues.
In a TCGA analysis presented along with preliminary data at the
The single-arm, open-label, nonrandomized phase 2 trial evaluated BPM31510 in combination with radiation and temozolomide in adult patients with newly diagnosed, pathologically verified GBM who had not received prior radiation, chemotherapy, immunotherapy, or targeted agents for the treated lesion.3
Eligible patients needed to be at least 18 years of age, have a Karnofsky performance score of at least 60, have a life expectancy of at least 3 months, and be 15 to 50 days removed from surgery.
The study opened with a dose-confirmation phase following a standard 3+3 design, with a starting BPM31510 dose of 110 mg/kg per week and 1 potential de-escalation to 66 mg/kg per week in the event of a dose-limiting toxicity, before advancing to the efficacy phase at the recommended phase 2 dose. Patients received a weekly 96-hour infusion of BPM31510 for 8 weeks, with prophylactic subcutaneous vitamin K1 administered before each week of therapy. Concurrent SOC radiotherapy and temozolomide at 75 mg/m² daily were initiated after 2 weeks of BPM31510, followed by up to 12 cycles of temozolomide.
The primary end point is progression-free survival at 6 and 12 months per RANO criteria, with OS and safety as secondary end points.
The intention-to-treat population at the time of the analysis comprised 51 patients, including 33 with MGMT-unmethylated tumors, 16 with methylated tumors, and 2 with unknown MGMT status.2 The median age was 64 years, and 28 patients (54.9%) were male.
BPM31510 was generally well tolerated in combination with standard chemoradiation, with no new drug-related serious adverse effects (AEs) observed among treatment-naive patients in the frontline setting.1
In the ITT population evaluable for safety (n = 51), treatment-emergent AEs (TEAEs) of any grade occurred in 96.1% of patients, and 36 (70.6%) experienced TEAEs related to study treatment.2 Grade 3 TEAEs, grade 4 TEAEs, and grade 5 TEAEs were reported at respective rates of 43.1%, 9.8%, and 5.9%. Serious TEAEs occurred in 33.3% of patients, including 9.8% of which were treatment-related.
TEAEs led to treatment discontinuation in 9.8% of patients and to death in 5.9% of patients, with 1 death (2.0%) considered related to study treatment. The most frequently affected system organ classes were nervous system disorders (70.6%) and gastrointestinal disorders (62.7%).
