CTNI-49. RHENIUM-(RE-186)-OBISBEMEDA [RE-186-NANOLIPOSOME] (186RNL) PHASE 2 FOR RECURRENT GLIOBLASTOMA (RGBM) VIA CONVECTION ENHANCE DELIVERY [CED

Abstract

Abstract BACKGROUND The Phase 1 ReSPECT-GBM trial observed a relative improvement in overall survival(OS) in rGBM with absorbed doses >100 Gray[Gy] compared to lower doses and historical controls. Statistical modeling was employed to understand the dose response relationship in planning the Phase2 trial. METHODS Phase1 data from cohorts1-6 of the 3 + 3 dose-escalation trial[N = 21] were utilized. Longitudinal MRI and SPECT/CT imaging were performed to assess treatment outcomes. SPECT/CT images were used to find the treatment volume. Variation in survival significance was assessed with log rank tests and an accelerated failure time (AFT) model. All statistical testing was 2-sided with a 5% significance level. RESULTS MTD/DLT was not reached in the first 6 cohorts. The 3 + 3 dosing (ml&mCurie) by cohort was 1: 0.66&1.0, 2: 1.32&2.0, 3: 2.63&4.0, 4: 5.28&8.0, 5: 5.28&13.4, 6: 8.8&22.3. Unadjusted for covariate information, median OS was 11.0 months(m) [95% Confidence Interval (CI) 5.0 m to 17 m]. Median OS varied significantly with absorbed dose; < 100 Gy: n = 9, median OS = 6.0 m, 95% CI 1.0m to 11m), ≥100 Gy: n = 12, median OS = 17.0 m (95% CI 8.0 m to 35.0 m), p < 0.001. After adjustment for age, baseline ECOG performance status, and baseline tumor volume, the AFT model predicted the OS to fold increase by 1.3 (95% CI 1.1 to 1.5)/100Gy increase in the absorbed dose (p < 0.001) and by 1.28 (95% CI 1.21 to 1.35 m)/10% increase in the treated to total tumor volume ratio (p < 0.001). The phase 2 trial, utilizing Cohort6 administered dose 22.3mCi in 8.8mL for tumor volumes ≤20mL [average absorbed dose of 374.5Gy], is ongoing--n = 5 accrued as of May 2023. CONCLUSION 186RNL therapy resulted in a dose and volume dependent impact on OS without significant toxicity. Based on these data, the Cohort 6 non-DLT dose advanced to Phase 2. Study progress will be reported.