CTNI-43. PHASE 1/2 RESPECT-GBM TRIAL OF RHENIUM (186RE) OBISBEMEDA IN RECURRENT GLIOBLASTOMA: SAFETY AND EFFICACY FROM THE PHASE 1 AND UPDATE ON PHASE 2

Abstract Rhenium (186Re) Obisbemeda (186RNL; Reyobiq), a novel radiotherapeutic consisting of 186Re encapsulated in nanoliposomes, is under investigation for convection enhanced delivery in recurrent glioblastoma (GBM) in the Phase 1/2 ReSPECT-GBM trial (IND 116117). The Phase 1 dose-escalation study, employing a modified 3 + 3 design, was completed and enrolled 29 patients across eight cohorts to determine the maximum tolerated dose (MTD), maximum feasible dose (MFD), and safety profile. Doses escalated from 1.0 mCi (0.66 mL) to 41.5 mCi, achieving a maximum absorbed tumor dose of 739.5 Gy. Only one dose-limiting toxicity (DLT; Grade 4 hemiplegia) was observed in Cohort 8, with the Cohort 6 dose (22.3 mCi) selected as the recommended Phase 2 dose (RP2D) due to its favorable safety profile. Across all patients treated in both Phase 1 and 2 (n=46 to date), most treatment-related adverse events (TRAEs; 114 total) were Grade 1 or 2, including lymphopenia (7.9%), cognitive disorder (7.0%), and headache (7.0%), with no treatment-related deaths or study discontinuations due to serious adverse reactions (SARs). Preliminary efficacy data from Phase 1 cohorts 1 to 6 (N=21) showed a median overall survival (mOS) of 17.0 months (95% CI 8.0–35.0) for patients receiving ≥100 Gy (n=12), compared to 6.0 months (95% CI 1.0–11.0) for those receiving <100 Gy (N=9), surpassing historical bevacizumab monotherapy outcomes (mOS ~7.4–9.2 months). The ongoing Phase 2 study has enrolled 23 of a planned 34 patients as of data cutoff, continuing to evaluate safety and efficacy at the RP2D. SPECT/CT imaging confirms high tumor-specific radiation retention, with minimal systemic exposure. These results support Reyobiq’s promising safety and efficacy profile, warranting further investigation as a novel therapeutic for recurrent GBM, addressing a critical unmet medical need.