LTBK-09. RESULTS OF BMX-HGG STUDY: A MULTI-INSTITUTIONAL, RANDOMIZED PHASE 2 CLINICAL TRIAL OF CONCURRENT CHEMORADIATION WITH OR WITHOUT BMX-001 IN PATIENTS WITH NEWLY DIAGNOSED HIGH GRADE GLIOMA

Abstract BACKGROUND Standard treatment for high grade glioma (HGG) remains neurosurgical resection followed by concurrent radiation therapy (RT) and temozolomide (TMZ). Overall survival (OS) for GBM is roughly 12-16 months. RT is associated with cognitive and quality of life (QoL) impairments. Advances are needed to improve OS while mitigating injury to the normal brain. BMX-001 is a novel metalloporphyrin that radiosensitizes cancer cells and radioprotects normal tissue. METHODS This multi-institutional, open-label, phase 2 trial randomized newly diagnosed HGG patients to receive RT/TMZ with or without BMX-001 (NCT02655601). Both arms received 6 weeks RT/TMZ (75 mg/m2). BMX-001 was administered as a loading dose of 28 mg sc before RT, followed by 14 mg twice weekly for 8 weeks. Randomization was stratified by tumor grade and institution. Key eligibility criteria include histologically confirmed HGG, age ≥ 18 years, and KPS ≥ 70%. The primary endpoint was OS. Key secondary/exploratory outcomes included cognition, QoL, and white matter integrity using advanced imaging. OS evaluation occurred after 84 deaths when a 1-tailed logrank test (α=0.2) had 90% power to detect a hazard ratio of 0.63. Two interim analyses and a final analysis were conducted using an O’Brien-Fleming stopping boundary. RESULTS Of the 160 patients randomized, 72.5% had GBM, and 62.5% were male. Analyses focused on 145 patients who completed RT/TMZ (74 with BMX-001, 71 without BMX-001). Median OS of BMX-001+RT/TMZ group (31.3 [95% CI, 21.6, not reached] months) was longer than RT/TMZ group (24.7 [95% CI, 19.6-32.6] months), HR=0.735; p=0.079 (significant at the predefined α level). Common toxicities (Grade 1-2) attributed to BMX-001 were injection site reactions (64), tachycardia (24), and pruritus (17) with no related Grade 4-5. Diffusion tensor MR imaging indicated mitigation of dose-related white matter damage in BMX-001+RT/TMZ group. CONCLUSIONS BMX-001 is safe, and there is improved OS in HGG patients receiving BMX-001.