CTNI-02. PRECLINICAL DATA AND INITIAL CLINICAL EXPERIENCE IN THE PHASE 1/2A DOSE ESCALATION TRIAL OF RHENIUM-186 NANOLIPOSOME (186RNL) IN LEPTOMENINGEAL METASTASES [LM]: THE RESPECT-LM TRIAL

Abstract

Abstract INTRODUCTION Leptomeningeal metastases (LM) is a clinical complication that occurs when cancer cells invade the leptomeninges and cerebrospinal fluid of patients with malignant tumors. Once diagnosed, limited treatment options exist, and survival is poor. Rhenium-186 Nanoliposome (186RNL) is a liposomal encapsulated beta emitter with a short path length of 1.8 mm, thereby allowing high specific activity brachytherapy with limited exposure to surrounding tissues. METHODS Preclinical efficacy was assessed using C6-Luc glioma cells in Wistar rats or MDA-MB-231 in Athymic Nude Rats via intraventricular injection. At 15 days post inoculation the animals were treated with 0.69 mCi of 186RNL. Absorbed doses were assessed with gamma camera imaging at 0h, 24h, and 48h post-treatment. Tumor growth was assessed by luciferase bioluminescence. A multicenter phase 1/2a dose (3 + 3 design) escalation trial was then initiated with 186RNL in LM patients to determine the maximum feasible dose, overall response rate (ORR) and overall survival distribution. RESULTS A significant difference in survival between the control and treatment groups (n = 8 each) was observed in the C6/Wistar model at 2 weeks post treatment, with 50% survival in the control group and 100% survival in the treatment group (p = 0.0087). Similar efficacy was observed in the MDA-MB-236/Athymic model. Thus far two patients have received 186RNL with 6.6 mCi in 5ml via Ommaya reservoir. Post treatment imaging shows full CSF distribution by 4 hours and persistence of activity through 7 days following administration. The dose was well-tolerated with no related AEs through day 56 following treatment. CSF cell count by BioCept analysis was reduced by > 90% with durability through day 28. CONCLUSION Intraventricular delivered 186RNL is promising for treatment of LM, with very early evidence of efficacy in patients. Enrollment is ongoing.