205 Treatment of Recurrent Glioblastoma (rGBM) Via Convection Enhanced Delivery (CED) With Rhenium (186Re) Obisbemeda (Rhenium-186 Nanoliposome, 186RNL): ReSPECT-GBM Phase 2 Trial Update

INTRODUCTION: 186RNL is a liposomally-encapsulated beta-emitting radiotherapy with high specific activity and excellent retention in tissue. Our previous Phase 1 study revealed up to 22.3mCi 186RNL by CED for recurrent GBM was well-tolerated with absorbed doses over 700Gy, with no dose limiting toxicities (DLTs) observed. The mOS in Phase 1 was 11 months across all cohorts and correlated with radiation absorbed dose and percent tumor treated. When dichotomized by radiation absorbed dose of 100Gy, the mOS was 17 months for >100 Gy (n=12), compared to 6 months for <100 Gy (n=9) (p=0.001). METHODS: A single arm, Phase 2, prospective trial was initiated in bevacizumab-naÏve, histologically confirmed rGBM. Subjects (n=17) underwent stereotactic biopsy followed by convection (2-4 catheters) of a single dose of 22.3mCi (8.80mL, 2.5mCi/mL) 186RNL. Whole-body planar and SPECT/CT imaging was performed for biodistribution and dosimetry; longitudinal MRI was performed to assess treatment outcomes. Patients were followed for safety, dose distribution, progression, and survival. RESULTS: A single dose of 186RNL was well-tolerated with minimal systemic absorbed radiation dose exposure. No patient had treatment-related adverse events (AEs) with outcome of death, and no patient withdrew due to AEs. Most AEs were mild (66.35%) and moderate (25%) and unrelated/unlikely-related to 186RNL. Average absorbed tumor dose was 309.14 Gy (range 62.60-739.5 Gy). Preliminary efficacy analysis (n=15) shows mOS was 13 months (m) (95% CI 5m-NA) and median progression free survival (mPFS) was 11m (95% CI 6m-11m), at the time of censoring consistent with Phase 1 data previously presented, versus historical-controls for bevacizumab and CED studies (∼8m). CONCLUSIONS: 186RNL therapy continues to show favorable dose-and-volume-dependent impacts on mOS without significant toxicity. Phase 2 is enrolling, and updated results will be presented.