TIPS-23 SAFETY AND FEASIBILITY RESULTS FROM A PHASE 1/2 CLINICAL TRIAL OF RHENIUM (186RE) OBISBEMEDA (186RNL) IN RECURRENT GLIOMA: THE RESPECT-GBM TRIAL

OBJECTIVES: 186RNL is BMEDA-chelated 186Re encapsulated in nanoliposomes. 186Re’s ~2 mm beta emission path length provides direct delivery of radiation therapy while sparing surrounding healthy tissue. 186RNL is delivered via convection enhanced delivery (CED) to achieve durable, localized tumor retention with high absorbed radiation doses. We present results from our ongoing ReSPECT-GBM trials (NCT01906385). METHODS: ReSPECT-GBM is a multi-center, sequential cohort, open-label, dose escalation, Phase 1/2 clinical trial in adults with recurrent glioma to evaluate the safety, tolerability, and activity of a single dose of 186RNL administered by CED. Following computer-assisted MRI guidance treatment planning for CED catheter placement, patients received a single administration of 186RNL before whole body planar and SPECT/CT imaging for dosimetry and distribution. Patients were followed for safety, progression, and survival. RESULTS: 25 patients across 8 dosing cohorts including 23 with recurrent GBM were treated with a single dose of 186RNL ranging from 1.0-41.5mCi. Average absorbed radiation dose (AARD) to the tumor was ~300 Gy over a wide range. Exposure outside the brain was negligible. A single dose of 186RNL was well-tolerated, with no dose limiting toxicities. No patient had treatment-related death or withdrawals and most AEs mild or moderate (Grade 1 or 2) and non-serious. 5 patients remain alive. mOS for all patients was >12 months, with an OS30 of 25% overall and 50% for those receiving >100Gy. Cox Proportional Hazards Ratio and Accelerated Failure Time modeling both demonstrate absorbed dose and percent tumor treated to significantly correlate with overall survival (p<0.003-0.0001). Five patients have subsequently enrolled in Phase 2 and all are alive. CONCLUSION: A single dose of 186RNL in recurrent glioma patients achieves high absorbed doses without significant toxicity, is well tolerated, and shows favorable OS. Cohort 8 and Phase 2 continue enrolling. Development progress and data will be reported.