TEST:

CNSide™ Cerebrospinal Fluid Assay

CNSide can be used to detect oncogene amplification on CSF-TCs of patients with LMD, and mutational status of the LMD tumor may differ from the original tumor biopsy. CSF-TC analysis may provide therapeutic insights that vary from the original tumor and could open the door to additional treatment targets for patients struck with LMD.

mOS was longer for patients eligible for intrathecal chemotherapy (HR: 0.189, 95%CI: 0.053-0.672, P = .010). This retrospective, real-world analysis of CNSide™ showed increased sensitivity versus cytology and provided clinically relevant molecular CSF analyses.

"Company acquired assets for the synergistic leptomeningeal metastases (LM) diagnostic platform, 'CNSide' and discussed potential partnering opportunities....Plus presented topline clinical trial data from the FORESEE trial which met its primary endpoint of clinical utility for the CNSide test in 40 patients with LM due to either breast or non-small cell lung cancer; a presentation of the full analysis is planned for the August 8-10 SNO/ASCO Meeting in Denver, CO."

In this single institution study, we detected a higher sensitivity to diagnose LMD with CNSide. This CSF assay identified 38% of LMD cases which were missed by standard CSF cytology and of note, 15% of the cases found with LMD were missed by both CSF cytology and MRI. In addition, CSF molecular testing using this assay demonstrated high concordance with tissue-based molecular testing.

CSF-TC density may carry prognostic value in patients with LMD from solid tumors. Integrating CSF-TC density into LMD patient risk-stratification may help guide treatment decisions.

The median survival for LMD patients was 16.1 m (5.2-NR). We show that CNSide can supplement the management of LMD in conjunction with SOC methods for the diagnosis, monitoring response to therapy, and identifying actionable mutations unique to the CSF in patients with LMD.

This retrospective, single-institution, real-world analysis of CNSideâ„¢ showed increased sensitivity versus cytology and provided clinically relevant, cell-based molecular CSF analyses.

Physicians will also indicate which component of the test aided in management, modeling other similar studies that measure the effect of serum biomarker results on clinical management of cancer. Secondary end points include diagnostic comparison to clinical evaluation, cytology, and radiographic results, and determining the sensitivity, specificity, PPV and NPV of CNSide in the detection of CSF tumor cells (cytology being the reference standard).

She had been taking adjuvant letrozole at the time of presentation. This case also highlights the benefits of using advanced and highly sensitive CSF assays to diagnose and surveil leptomeningeal disease and to assess HER2 signaling. This case is well-timed especially in the era of next-generation, CNS penetrating, potent HER2-directed antibody-drug conjugate like T-DXd which can mount antitumor activity even with minimal HER2 expression in tumors.

We observed concordance and heterogeneity in the status of actionable mutations between the CSF, peripheral blood, and systemic metastatic tumor tissue. Larger studies are needed to assess the clinical utility of these observations, particularly with the development of several novel targeted agents that are CNS-penetrant.

"Biocept...announces the full enrollment of 40 subjects with breast or non-small cell lung cancer (NSCLC) who have suspicious or confirmed leptomeningeal metastases (LM) in the feasibility phase of its prospective FORESEE clinical trial (NCT0414123). This trial is evaluating the performance of Biocept’s proprietary CNSide assay in monitoring the response to therapy of LM, a cancer in the membranes that surround the brain and spinal cord, and assessing its impact on treatment decisions made by physicians."

"Biocept, Inc...announces the signing of a non-exclusive licensing agreement for CNSide™ with Plus Therapeutics, Inc...which expands the comprehensive laboratory services agreement between the two companies that was announced in June 2022....This new agreement allows for Plus to perform CNSide testing during its clinical trials and commercially, subject to regulatory approval....Plus will pay Biocept an upfront fee of $150,000 in stock, plus $6,000 per CSF tumor cell enumeration analysis performed in Biocept’s CLIA-certified and CAP-accredited laboratory prior to the completion of the technology transfer. Once the technology transfer is complete, Plus will pay Biocept $300,000 plus fees on a sliding scale starting at $2,800 for each CNSide test they perform. The license agreement also gives Plus the option to negotiate for third-party exclusivity with a $1,000,000 payment to Biocept."

"Biocept...announces that its CNSide cerebrospinal fluid assay was featured in two oral presentations at the 2023 SNO/ASCO CNS Cancer Conference on Saturday, August 12."

"Biocept...announces a poster presentation at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting underway in Chicago showing the ability of CNSide™ to detect rates of leptomeningeal metastases (LM) compared with standard CSF cytology from lumbar puncture. The poster, titled 'Evaluating the diagnostic performance of leptomeningeal diagnosis with CNSide compared to standard cytology,' was presented by Dr. Haley Appel at the Miami Cancer Institute, Baptist Health South Florida, on Saturday, June 3. The abstract of the poster is available here, including a link to the full poster which is accessible to ASCO registrants."

In the largest, retrospective, single institution, real-world study, implementation of CNSide showed increased sensitivity relative to standard cytology and increased specificity relative to EANO criteria, and provided clinically relevant, cell-based molecular and cell-free DNA analyses. CNSide increased the diagnostic yield by 56.5%.

"Biocept...announces enrollment of the first patient in the FORESEE clinical trial with the Company’s proprietary cerebrospinal fluid assay CNSide (NCT05414123). This first patient was seen at the UT Southwestern Medical Center, one of the largest and most respected hospitals in the nation."

"Biocept...announces a collaboration agreement to participate in an investigator-initiated, non-therapeutic pilot study to evaluate the cerebrospinal fluid tumor and immune cell microenvironment in patients with metastatic breast cancer and brain metastases and/or leptomeningeal disease. The study is designed to identify biomarkers associated with central nervous system (CNS) metastasis, enabling a better understanding of treatment response, prognosis, and treatment resistance that may improve the management of CNS disease in patients with metastatic breast cancer...Results from cerebrospinal fluid using Biocept’s CNSide assay and matched patient blood samples will be analyzed and compared to detect and characterize cancer in the cerebrospinal fluid with the goal of identifying new targets and to guide therapeutic decisions."

"Biocept, Inc...announces the expanded commercial availability of CNSide for patients with metastatic melanoma. Previously validated for lung, breast, and all other carcinomas, Biocept’s CNSide is a proprietary CSF assay designed to better detect and inform treatment decisions for patients with metastatic cancers involving the central nervous system (CNS)...The new CNSide for melanoma assay uses a novel antibody cocktail optimized for the capture of melanoma cells based on unique cellular characteristics."

"Biocept, Inc...announces an hour-long webinar to be held October 14 at 1 p.m. Eastern time featuring case studies presented by leading neuro-oncologists who have used the company’s CNSide assay in the management of patients with confirmed or suspected central nervous system metastasis."

"Plus Therapeutics, Inc...and Biocept, Inc...announce a multi-year agreement to employ Biocept’s cerebrospinal fluid (CSF) assay CNSide1 in Plus Therapeutics’ ReSPECT-LM Phase 1/2a dose-escalation clinical trial of Rhenium-186 NanoLiposome (186RNL) for the treatment of patients with leptomeningeal metastases (LM), which is cancer in the membranes that surround the brain and spinal cord."

"Biocept, Inc...highlighted the ability of its CNSide™ cerebrospinal fluid (CSF) assay to aid in therapeutic research programs for metastatic brain cancer in a presentation at the Molecular & Precision Med Tri-Con meeting. The company is also exhibiting (booth #508) at the conference, which is the leading international meeting for the precision medicine community, Feb. 21-23, 2022, in San Diego."

"Biocept, Inc...presented a study demonstrating the ability of its CNSide™ assay to identify HER2 and other actionable tumor alterations in the cerebrospinal fluid of patients with breast cancer and leptomeningeal disease (LMD). The poster was chosen for a Spotlight Presentation at the San Antonio Breast Cancer Symposium on Dec. 8, 2021."

"Biocept...announced the presentation of a multi-institutional case series showing that its CNSide™ cerebrospinal fluid assay helps physicians monitor treatment response and detects actionable mutations in patients with metastatic breast cancer and leptomeningeal disease (LMD). The poster will be presented virtually at the Society for Neuro-Oncology Annual Meeting...At diagnosis, CNSide detected cancer cells in three of three patients, compared with two of three patients for cytology. (The fourth patient was diagnosed before CNSide was available.) CNSide detected CSF tumor cells in all eleven measurements taken, compared to six of eleven using cytology. Throughout treatment, CNSide showed a decrease in CSF tumor cells in all four patients, ranging from 99.7% to 100%, corresponding with an improved clinical response."

Our experience suggests that using CNSide for quantitative CSF tumor cell detection may aid in diagnosing LMD, as well as in quantifying response to treatment particularly in the setting of intrathecal therapy. However, larger prospective clinical trials are needed to establish the role of CNSide in the diagnosis and management of LMD.

HER2 amplification is frequently found in breast cancer patients with LMD and can be reliably detected in tumor cells isolated from CSF. Evaluation of HER2 status in CSF-TCs allows treating physicians the opportunity to rapidly confirm the presence of this biomarker and select a more effective targeted therapy against HER2 in patients who present with life-threatening complications of breast cancer. Additional studies are needed to fully establish the clinical utility of CNSide when using various anti-HER2 therapies or therapy combinations to treat breast cancer patients with LMD.