LOCL-08 SAFETY AND FEASIBILITY OF RHENIUM-186 NANOLIPOSOME (186RNL) IN RECURRENT GLIOMA: THE RESPECT™ PHASE 1 TRIAL

Abstract

Abstract BACKGROUND Liposomal rhenium-186 (186RNL) is a potent source of electrons with short path length, low dose rate, high radiation density and gamma emission. Preclinically, 186RNL via convection enhanced delivery (CED) achieves very high doses of targeted radiation and a wide therapeutic index. We report the updated results of ReSPECT, the first in man, dose escalation phase 1 trial of 186RNL in recurrent glioma. METHODS Following computer assisted treatment planning and placement of intracranial catheter(s), we performed a single administration of 186RNL by CED. Whole body planar and SPECT/CT imaging was obtained on days 1-8 following treatment for dosimetry and distribution. Patients were followed for safety, progression and survival. RESULTS Twenty-one patients across 7 cohorts received 1.0-22.3mCi in a tumor volume of 0.6-8.80mL. Mean tumor volume was 8.3mL (0.9-22.8mL). Patients had a mean of 1.7 recurrences, 5 with prior bevacizumab. 19 (91%) were grade 4 gliomas, and 100% were after cohort 4. We used a CED rate of 5-20µl/min per catheter, with 1-4 catheters per patient. Tumor mean absorbed radiation dose was 255Gy (8.9-740Gy) while exposure outside the brain was negligible. The mean percentage tumor in the treated volume (Tu/Tv) was 60.3% (19.8%-100%). Thus far, we have observed no dose limiting toxicities, one grade 3 treatment related adverse event (AEs), and the majority of AEs were mild in intensity. The incidence and severity of AEs did not correlate with increasing dose. Mean Tu/Tv in patients not receiving prior bevacizumab was 75% vs. 48% in those that had. Thus far, overall survival (OS) in 16 bevacizumab naïve patient is 49 weeks with 7 patients still alive and a positive correlation of OS to Tu/Tv. CONCLUSIONS 186RNL achieves high absorbed doses without significant toxicity with favorable overall survival. Updated delivery feasibility, safety and overall survival will be presented.