Octs-11 Phase 1 Dose Escalation of Rhenium (186re) Obisbemeda (Rhenium Nanoliposome,186rnl for the Treatment of Leptomeningeal Metastases (Lm): Ongoing Clinical Study Update for Initial Safety and Feasibility

BACKGROUND Leptomeningeal metastases (LM) is a devastating systemic cancer complication most often seen with breast, lung, renal cell, and melanoma, with limited treatment options and poor survival. Rhenium (186Re) Obisbemeda (186RNL) provides the combination of effective therapeutic beta radiation, simultaneous gamma-decay for imaging, and ~89.2-hour physical half-life for optimal radiation delivery. An ongoing clinical trial update for the Phase 1 dose escalation study (Cohorts 1-5) is presented. METHODS ReSPECT-LM is a Phase 1 dose escalation study for patients with LM from any primary cancer. Adult patients are given a single dose of 186RNL via intraventricular catheter (Ommaya reservoir) in an outpatient setting to determine the maximum tolerated/feasible dose (MTD/MFD), safety, and tolerability. Subjects received 6.6, 13.2, 26.4, 44.10, or 66.14 mCi of 186RNL (Cohort 1-5, respectively). RESULTS Doses were well-tolerated with no treatment-related serious adverse events (SAEs); the majority of AEs were Grade 1 and 2. The MTD/MFD has not been reached. CSF tumor cell enumeration assays (CNSide test) were performed with a maximum reduction over baseline seen at Day28. Radiation absorbed doses were calculated for the ventricles, cranial subarachnoid space, and spinal fluid and showed a linear increase with administered dose, with liver and spleen remaining low. To date, neurological signs and symptoms from LM were reported to improve by investigators and patients. Cohort 5 is completing its enrollment and subsequent analysis. CONCLUSION A single dose of 186RNL for patients with LM is well tolerated, has high absorbed doses to the treatment area with low organ dose, and shows promising positive clinical improvement and reductions in tumor cell count. Enrollment to Cohort 6 (87.97 mCi) will follow Cohort 5’s data safety review; the current development status of the Phase 1 study will be reported.