Validation of Novel Therapeutic Approach for Leptomeningeal Metastases

ABSTRACT Leptomeningeal Metastases (LM) is a condition in which tumor cells from a primary tumor metastasize, invade the subarachnoid space (SAS) and spread throughout the cerebrospinal fluid (CSF), resulting in seeding along the meninges, brain and spinal cord. LM represents a devastating event of cancer progression. There are 30,000 cases annually and currently no cure, with average survival of 3-6 months with current therapies. Reduction in tumor burden is the primary goal to extend survival and quality of life. Minnetronix, a medical device development and manufacturing company, proposes this Phase II STTR in collaboration with experts from the Duke Cancer Institute and Neurosurgery Department at Duke University. Phase I demonstrated the dramatic results of Neurapheresis, a CSF processing platform, with the ability for targeted circulation of chemotherapeutics (such as Methotrexate, MTX), along with rapid clearance of tumor cells both in vitro and in vivo, in a rabbit LM model. Phase II will optimize and validate a tailored human system to deliver the first-ever platform for LM patients. It will allow for circulation of chemotherapeutic agents (MTX) intrathecally, control of drug concentration and toxicity, rapid removal of tumor cells from the CSF, sampling of CSF to follow circulating tumor cell reduction and drainage of CSF to normalize ICP. Specific Aim 1 will understand and optimize the dosing regimen of intraventricularly delivered MTX during Neurapheresis in a cranial/spinal model and develop a PK model. Specific Aim 2 will demonstrate the safety and efficacy of Neurapheresis filtration and MTX circulation in a pivotal rabbit LM model, refine the PK model, and develop a PK/PD model. Specific Aim 3 will complete the development of the validated Neurapheresis system for intrathecal MTX circulation and targeted removal of cells from the CSF and prepare the system for human trials. Neurapheresis is an innovative, new therapeutic option that provides direct access to the CSF and allows for active circulation of intraventricularly delivered intrathecal agents, combined with targeted reduction in tumor burden. This treatment is complementary and does not replace standard of care (SOC) interventions with systemic regimens. Successful completion of this Phase II STTR will provide Minnetronix with the ability to complete development of a GLP-quality system for the treatment of LM patients. Concurrent regulatory and clinical study planning will be conducted to prepare for an investigational device exemption (IDE) application at the end of Phase II. The long-term goal of the project is to develop a novel tumoricidal approach to reduce morbidity and mortality for LM patients worldwide.NARRATIVE In this Phase II STTR, Minnetronix plans to validate an innovative, new therapeutic platform for treating a devastating central nervous system (CNS) metastatic disease. Leptomeningeal metastases (LM) is a condition in which cells from a primary solid or hematological tumor spread throughout the cerebrospinal fluid (CSF) and seed the leptomeninges. It affects 30,000 patients in the US annually, with a median survival of 3-6 months with current therapies. This project will improve lives by providing the first-ever tumoricidal platform, allowing for active circulation of chemotherapeutic agents, and safely targeting the CNS tumor burden.