According to a recent press release from Biospace, the first cohort of the ReSPECT-LM trial has officially completed enrollment. This trial focuses on Rhenium-186 NanoLiposome (186RNL) as a treatment for leptomeningeal metastases (LM), which occur when cancer cells travel from their original site – whether that be breast cancer, melanoma, or lung cancer – to the cerebrospinal fluid (CSF) or leptomeninges. About 5% of those with cancer develop LM and face a 2-year survival rate of 3%.
About the Study
ReSPECT-LM is a phase 1/2a clinical trial that investigates 186RNL as a treatment for LM. It is dose-escalating, open-label, multicenter, single dose, sequential cohort, and utilizes a modified Fibonacci 3+3 study design in order to evaluate the efficacy, safety, maximum feasible dose (MFD), and maximum tolerable dose (MTD) of one administration of 186RNL. Patients will be given the investigational drug via IV catheter following chemotherapy, radiation, and/or surgical treatment.
To be more specific, researchers will focus on the primary endpoints of the severity and incidence of (serious) adverse events (AEs) and dose limiting toxicities. Additional attention will be paid to the secondary endpoints, which include overall survival (OS), duration of response (DOR), progression-free survival (PFS), and overall response rate (ORR).
This clinical trial follows encouraging preclinical data, in which two animal models of LM showed reduced tumor burden and tolerated doses as high as 1,075 Gy without any visible significant toxicity. Additionally, the FDA has already granted its Fast Track designation to 186RNL for LM, which means that its developer, Plus Therapeutics, will have more communication with the FDA, rolling review, and eligibility for Priority Review and Accelerated Approval.
Now, Pulse has said that the next clinical and enrollment updates are to come in the third quarter of this year.
Administered as a single dose via an Ommaya reservoir, 186RNL is a nanoscale compound paired with a unique chelated radioisotope. One portion of the compound, Rhenium-186, is a dual energy emitter that offers high precision, a low dose rate that is safer for healthy tissue, and a high radiation density that allows it to overwhelm sitting DNA repair mechanisms. Further, the emission of dual energy makes it possible to both see and evaluate the administration of the drug in real-time.
About Leptomeningeal Metastases (LM)
According to Memorial Sloan Kettering Cancer Center, LM occur when malignant cells from a patient’s cancer, regardless of what type of cancer they have, travels to the CSF or leptomeninges. These metastases grab on to nerve cells as the exit the brain and pass the spinal cord, which then leads to numbness and weakness. Other symptoms are dizziness, nausea, double vision, trouble thinking, vomiting, headaches, seizures, loss of bladder/bowel control, pain in the extremities, difficulty with swallowing and speaking, and weakness and/or lack of coordination in the extremities. Patients may have one or more of these symptoms, but they will most likely not have them all. A complication that may occur is a clogging of the leptomeninges, which can stop CSF from flowing properly and building up in the brain.