LMD-13. ReSPECT-LM: Maximum tolerated dose, safety, and efficacy of intraventricular Rhenium-186 Nanoliposome ((186)RNL) for leptomeningeal metastases

INTRODUCTION: Leptomeningeal metastases (LM) are a rare but typically fatal complication of advanced cancer that affects the fluid-lined structures of the central nervous system and are diagnosed in approximately 5 percent of patients with metastatic cancer. With survival measured in weeks to months, novel approaches are needed that can both improve quality and quantity of life. Rhenium-186 NanoLiposome (186RNL) permits the selective delivery of beta-emitting radiation of high specific activity directly to the tumor. In a Phase 1 trial in adults with recurrent glioblastoma (NCT01906385), the mean absorbed dose to the tumor when coverage was 75% or greater (n=10) was 392 Gy (CI 306 – 478). Thus far, the therapy has been well tolerated with one possible treatment-related serious adverse event, cerebral edema, that resolved after steroid treatment. METHODS: This is a two-part, Phase 1 dose-finding study followed by an expansion cohort to explore efficacy. Part 1 will enroll up to 21 subjects to characterize the safety and tolerability of a single dose of 186RNL administered intraventricularly via an Ommaya reservoir and to identify a maximum tolerated dose (MTD) / maximum feasible dose (MFD) for future studies. The dose limiting toxicity period is 28 days post infusion. Part 2 will independently evaluate 186RNL in 2 different cohorts: Cohort A: up to 20 subjects with a diagnosis of LM from primary breast cancer; Cohort B: up to 20 subjects with a diagnosis of LM from primary non-small cell lung cancer. The primary endpoint is to estimate the anti-tumor activity of 186RNL as a single agent. Secondary endpoints are to characterize the pharmacokinetic and dosimetry profile of a single dose of 186RNL, determine the overall response rate (ORR) based on CSF and radiographic findings, and to describe the survival distribution. Planned enrollment will begin in H2 2021.