CTNI-63. RHENIUM (186RE) OBISBEMEDA (RHENIUM NANOLIPOSOME,186RNL) FOR THE TREATMENT OF LEPTOMENINGEAL METASTASES (LM): SUMMARY OF THE PHASE 1 DOSE ESCALATION STUDY AND PHASE 2 ADMINISTERED DOSE SELECTION

Abstract BACKGROUND Leptomeningeal metastases (LM) is a devastating systemic cancer complication most often seen with breast, lung, 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 ~90-hour physical half-life for optimal radiation delivery. A summary of the Phase 1 dose escalation study, expected to be completed, will be 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. Seven administered dose cohorts in a 3 + 3 design, from 6.6 mCi to 109.96 mCi, were anticipated. RESULTS For the first 5 cohorts, doses were well-tolerated; most AEs were Grade 1 and 2 with 1 DLT (Cohort 5) at time of abstract submission. CSF tumor cell enumeration assays were performed with a maximum reduction over baseline seen at Day 28. 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. Neurological symptoms were reported to improve. We expect the Phase 1 conclusion and the RP2D to be determined for conference reporting; additionally, based on duration of benefit seen during the Phase 1, a multidose paradigm will be initiated to extend benefit. CONCLUSION A single dose of 186RNL for patients with LM has been well-tolerated, with high absorbed doses to the treatment area, acceptable organ doses, and promising clinical improvement and reductions in tumor cell count. Phase 2 is expected to begin enrollment by Q4 2024. Additionally, based on these data, a Phase 1 multidose study is planned to be initiated this year.