Radt-20. report of the respect-gbm™ phase i/iia dose escalation trial of rhenium-186 nanoliposome (186rnl) in recurrent glioma via convection enhanced delivery (ced) & planned phase iib trial

Abstract A phase I/IIa dose escalation trial was initiated to determine the safety and recommended phase II dose (RP2D) of 186RNL in patients with recurrent glioma. Liposomal rhenium-186 (186RNL) is a source of high energy beta particles and gamma photons with attractive properties for brain CED.Patients with biopsy proven recurrent glioma had computerized treatment planning and placement of up to 4 intracranial catheter(s). Each patient received a single administration of 186RNL by CED. Whole body planar and SPECT/CT imaging from days 1-8 following treatment was performed. Patients were followed for safety, sufficiency of delivery and overall survival. Twenty-one patients across 6 dose escalation cohorts received 1.0-22.3mCi in a volume of 0.6-8.8mL. Mean tumor volume was 8.3mL, patients were heavily pretreated (mean 1.7 recurrences) with poor prognostic factors. There were no CED failures. Mean absorbed radiation dose to the tumor (MARDT) was 271Gy. No dose limiting toxicities were observed. Patients were stratified by MARDT. Those receiving > 100Gy MARDT (n=12) had a median and mean overall survival of 129.9 (95% CI 35.1 to 169.3) and 99.5 ± 19 weeks respectively with 3 patients alive. Patients receiving ≤ 100Gy MARDT (n=9) had a median and mean overall survival of 22.4 (95% CI 6.6 to 45.4) and 24.7 ± 4.8 weeks respectively, none are alive. Kaplan Meier analysis of overall survival for patients receiving MARDT greater than 100Gy vs. those with ≤ 100Gy showed a statistically significant difference in overall survival (p< 0.001).A single administration of 186RNL by CED in recurrent glioma patients is feasible, safe, and potentially effective in increasing overall survival when > 100Gy radiation is delivered to the tumor. A RP2D of 22.3mCi in 8.8mL was selected for patients with tumor size of ≤ 15mL in the planned phase 2b trial. The PIIb trial design and comparative survival data will also be presented.