fbpx Leptomeningeal Metastases - Plus Therapeutics (PSTV)
Leptomeningeal Metastases

A rare, difficult-to-treat cancer of the
central nervous system (CNS).

Leptomeningeal Metastases (LM), also known as leptomeningeal carcinomatosis, is a late-stage cancer complication in which cancer cells spread from four primary cancers – breast, lung, melanoma and gastrointestinal – to the CNS. It is usually found in either the leptomeninges or cerebrospinal fluid (CSF), often goes undiagnosed due to a lack of symptoms, and causes neurological complications such as difficulty thinking, double vision, and headaches.

Incidence

110K

cases diagnosed each year in the U.S.1

Survival

7%

of patients survive the first year from diagnosis 2

Current Treatment Approaches

There is considerable variation in the resource-intensive treatment of LM, with no standard of care and usually significant healthcare costs at the one-year mark after diagnosis. Typically, treatment includes radiation therapy to the affected sites, followed by chemotherapy.

Patients often face the difficult choice between toxic therapies
and a limited life expectancy.

The risk of significant side effects from entire neuroaxis radiation therapy generally outweighs the benefits in this relatively radioresistant tumor. Focal radiation therapy relieves neurological symptoms but has no significant effect on survival.
Due to the relatively short median survival, today, patients must carefully evaluate whether they would prefer to prolong life with significant side effects or let the disease take its course while remaining relatively pain-free.

The Opportunity

To extend the life of patients with LM and
maintain their quality of life at the same time.

Compared to similar radiotherapeutics, 186RNL may potentially clear the body in a quicker amount of time – less than a day. The use of the radioisotope, Rhenium-186, also appears to be a better match for this application than other radioisotopes, as it has a 3.8-day half-life that facilitates higher dose amounts to be absorbed in the CNS before entering the circulatory system.
Our lead drug candidate, 186RNL, is a radiotherapeutic designed to inject high doses of radiation directly into the CNS via an intraventricular Ommaya reservoir. By targeting the tumor more precisely, we expect 186RNL may minimize radiation exposure to normal tissues, exhibit a high safety margin with minimal risk of bone marrow suppression, and be able to treat most patients with LM.
186RNL is currently being investigated in our ReSPECT-LM Phase 1 Clinical Trial, where patients with LM will be administered a single dose on an outpatient basis. In preclinical models, 186RNL showed promising efficacy levels and no maximum tolerable dose was reached.