CTSI-06 PHASE 1 DOSE ESCALATION OF RHENIUM (186RE) OBISBEMEDA (RHENIUM NANOLIPOSOME,186RNL (REYOBIQ) FOR THE TREATMENT OF LEPTOMENINGEAL METASTASES (LM): CLINICAL STUDY RESULTS FOR SAFETY AND EFFICACY

Abstract Leptomeningeal disease (LMD) is a devastating cancer complication with poor survival. Rhenium obisbemeda (Reyobiq) is a liposomal encapsulated radiopharmaceutical evaluated in a phase 1 dose escalation study (ReSPECT-LM) for patients with LMD from any cancer. Patients received a single dose of Reyobiq via intraventricular route (Ommaya reservoir) to determine the maximum tolerated/feasible dose, safety, and tolerability using a 3 + 3 design. A total of 29 subjects received 6.6, 13.2, 26.4, 44.10, 66.14, or 75 mCi of Reyobiq (cohorts 1-6, respectively). No dose limiting toxicity (DLT) was observed in cohorts 1-4, with 1 DLT in each of cohorts 5 and 6 of grade 4 cytopenia. After safety review, dose escalation and enrollment was concluded with cohort 6 and the recommended phase 2 single dose was 44 mCi. The majority of adverse events across the trial were Grade 1 and 2. There were no serious adverse events reported in cohort 4 (n=6). A dose dependent increase was observed in the absorbed dose to the cranial and spinal subarachnoid space reaching a mean of 272 Gy in cohort 6. Radiographic response data available for 17 patients showed 5 partial responses and 8 stable disease through day 112 (76% benefit rate). Additionally, a clinical response with decrease in disease symptoms was noted in 2/15 evaluable patients (13%), and 11 showing stable symptoms through day 112 (clinical benefit rate of 87%). CSF tumor cell enumeration (TCE) assays (CNSide test) were performed with a maximum reduction over baseline of 100% seen at Day 28. Five of the 7 patients with a TCE response >80% survived at least 1 year. Across cohorts 1-4 (20 patients) median overall survival was 9 months, comparing favorably with literature reports of ~4 months. Reyobiq shows excellent safety and promising activity for LM. Both single-dose expansion and multidose studies are planned.