CNSide Diagnostics, a subsidiary of Plus Therapeutics, presented data from the FORESEE trial at the 2024 Society for Neuro-Oncology (SNO) Annual Meeting, highlighting the utility of the CNSide Cerebrospinal Fluid (CSF) Assay in diagnosing and guiding clinical decision-making for patients with leptomeningeal metastases (LM) from breast and non-small cell lung cancer.
The FORESEE study (NCT-5414123) was a multi-center, prospective clinical trial that enrolled patients with breast or non-small cell lung cancer (NSCLC) who had suspicious or confirmed leptomeningeal metastases (LM). The study evaluated the performance of CNSide in monitoring the LM’s response to treatment and to assess the impact of CNSide on treatment decisions made by physicians.
Key Findings from the FORESEE Trial
The FORESEE trial achieved its primary endpoint, demonstrating that CNSide influenced treatment decisions in over 90% of cases evaluated, surpassing the predetermined 20% primary endpoint target. The assay demonstrated enhanced sensitivity in detecting tumor cells (80%) compared to CSF cytology (29%) in patients with LM. CNSide identified actionable mutations in the CSF, such as HER2 amplification, influencing 24% of therapeutic selection decisions. The assay exhibited high specificity, with no tumor cells detected in patients without LM, and demonstrated improved Negative Predictive Value in ruling out LM (25%) compared to CSF cytology (10%). Notably, CNSide revealed HER2 positivity in LM tumors in 60% of breast cancer patients with HER2-negative primary tumors, informing physician treatment strategies.
Clinical Significance
Leptomeningeal Metastases (LM) is a rare complication of cancer in which the primary cancer spreads to the cerebrospinal fluid (CSF) and leptomeninges surrounding the brain and spinal cord. All malignancies originating from solid tumors, primary brain tumors, or hematological malignancies have this LM complication potential with breast cancer as the most common cancer linked to LM, with 3-5% of breast cancer patients developing LM. The incidence of LM is on the rise, partly because cancer patients are living longer and partly because many standard chemotherapies cannot reach sufficient concentrations in the spinal fluid to kill the tumor cells; yet, there are no FDA-approved therapies specifically for LM patients, who often succumb to this complication within weeks to several months if untreated.
According to Marc H. Hedrick, M.D., President and CEO of Plus Therapeutics, current gold standard CSF cytology lacks the sensitivity needed to reliably diagnose LM in most clinical situations and lacks utility for disease monitoring. The FORESEE trial suggests that CNSide may be a useful tool in accurately identifying all patients with LM, ruling out patients at risk, and enhancing the disease management and monitoring of LM.
About the CNSide CSF Assay Platform
The CNSide Cerebrospinal Fluid (CSF) Assay Platform consists of four laboratory developed tests (LDTs) used for diagnosis, treatment selection, and treatment monitoring of patients with Leptomeningeal Metastases (LM) from carcinomas or melanoma. The CNSide platform facilitates tumor cell detection / enumeration and biomarker identification using cellular assays (immunocytochemistry (ICC) and fluorescence in situ hybridization (FISH)) and molecular assays (next generation sequencing (NGS)). The CNSide CSF tumor cell enumeration LDT is currently being used in the ReSPECT-LM trial as an exploratory endpoint and is anticipated to become commercially available in 2025.
