ACTR-28. PHASE 1 DOSE ESCALATION TRIAL OF THE SAFETY OF BMX-001 CONCURRENT WITH RADIATION THERAPY AND TEMOZOLOMIDE IN NEWLY DIAGNOSED PATIENTS WITH HIGH-GRADE GLIOMAS

BACKGROUND BMX-001 (MnTnBuOE-2-PyP5+) is a metalloporphyrin with differential action in response to oxidative stress caused by radiation therapy (RT)and chemotherapy, both critical components in the treatment of high-grade gliomas (HGG). In preclinical studies, BMX-001 functions as a radioprotectant of normal tissue, for example protection of central nervous system white matter and radiosensitizer of human glioblastoma (GBM) xenografts. Therefore, we underwent a phase 1 study to evaluate safety of BMX-001 in newly diagnosed patients with HGG receiving concurrent RT and temozolomide (TMZ). METHODS We performed a phase 1, single-center, dose-escalation study of BMX-001 in combination with concurrent RT (daily fractions of 1.8–2 Gy given 5 days/week for 6 weeks for a total of 59.4–60 Gy) and TMZ (75 mg/m2 daily X 42 days). We administered BMX-001 as a subcutaneous injection at a loading dose before start of RT and TMZ and then subsequently 2 times/week for 8 weeks. Primary endpoint was determination of the maximum tolerated dose (MTD). We assessed safety using National Cancer Institute Common Terminology Criteria for Adverse Events 4.03. RESULTS We enrolled 15 subjects with GBM (WHO grade IV) with age range of 19 to 80 years. BMX-001 at 42 mg loading dose and 20 mg subsequent dose was the maximum administered dose and 28 mg loading dose and 14 mg subsequent dose was the MTD. Sinus tachycardia (grade 3) was the dose-limiting toxicity at 42 mg loading dose (n=1). Only other related grade ≥ 3 event seen was hypotension (grade 3) (n=1). Most common related toxicity was grade 1 injection site reaction (n=7). CONCLUSIONS BMX-001 with RT plus TMZ and post-RT TMZ for patients with newly diagnosed HGG was safe and well-tolerated. Phase II study with BMX-001 in combination with concurrent RT and TMZ in subjects with newly diagnosed HGG is planned.

Duke Scholars

Author Ivan Spasojevic Medicine, Medical Oncology