EPCT-18. A TWO-PART, PHASE 1 STUDY OF RHENIUM-186 NANOLIPOSOME (186RNL) DELIVERED BY CONVECTION ENHANCED DELIVERY FOR RECURRENT, REFRACTORY, OR PROGRESSIVE EPENDYMOMA AND HIGH-GRADE GLIOMA (HGG) AND NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

Ependymoma, HGG, and DIPG are gliomas that are often difficult to treat, frequently aggressive, and often carry an extremely poor prognosis. While external beam radiation therapy (EBRT) remains a central component of the management of pediatric gliomas, it is limited by tolerance of the surrounding normal brain tissue. Rhenium-186 NanoLiposome ((186)RNL) permits the selective delivery of beta-emitting radiation of high specific activity with excellent retention in the tumor. In a Phase 1 trial in adults with recurrent glioblastoma (NCT01906385), the mean absorbed dose to the tumor when coverage was 75% or greater (n=10) was 392 Gy (CI 306 – 478). Thus far, the therapy has been well tolerated, no dose-limiting toxicity has been observed, and no treatment-related serious adverse events have occurred despite markedly higher absorbed doses than typically delivered by EBRT (n=18). METHODS: This is a two-part, Phase 1 dose-finding study followed by an expansion cohort to explore efficacy. Part 1 will enroll up to 18 subjects to determine the maximum feasible dose (MFD) of (186)RNL administered by convection enhanced delivery (CED). Tumor size will be limited to a diameter of 4 cm in the longest axis and a volume of 34 mL. The dose limiting toxicity period (DLT) is 28 days post infusion. Part 2 will independently evaluate (186)RNL in 3 different cohorts: Cohort A: up to 12 subjects with a diagnosis of recurrent, refractory, or progressive ependymoma; Cohort B: up to 12 subjects with a diagnosis of recurrent, refractory, or progressive HGG; Cohort C: up to 15 subjects with newly diagnosed DIPG. The primary endpoint is overall response rate (ORR) by Radiographic Assessment in Pediatric Neuro-Oncology (RAPNO) criteria. Secondary endpoints are PFS-24 and OS-24 in Cohort A and PFS-12 and OS-12 in Cohorts B and C. Planned enrollment will begin in H2 2021.