Ogct-02 a Translational Observational Biorepository and Management Study in Patients With Breast Cancer Leptomeningeal Metastasis: The Biolept Study

BACKGROUND Leptomeningeal disease (LMD) is a devastating complication of breast cancer (with high rates of morbidity and mortality) and breast cancer accounts for almost 30% of LMD cases. Despite the advances in the treatment of breast cancer, unfortunately there are still limited treatment options available. AIMS We designed the BioLept clinical trial for patients with breast cancer LMD with three main purposes: 1) Improve the timelines for patients to obtain diagnostic work up and treatment recommendations 2) Track patient outcomes (using a novel de-centralized clinical trial platform) 3) Collect biospecimens for translational correlative work focusing on CSF ctDNA (to optimize therapy and understand disease biology). OUTCOME MEASURES We will evaluate the sensitivity and concordance between different diagnostic tests, including imaging (MRI) and biomarkers (CSF cfDNA and cytology, blood-based ctDNA and tissue-based NGS), with the hypothesis that combining different tests enhances sensitivity. We will also describe the accuracy of these tests in monitoring response to therapy. We aim to establish an accelerated infrastructure whereby patients may achieve rapid diagnostics and treatment recommendations (within 7 days) from a multi-disciplinary molecular tumor board using an inclusive de-centralized clinical trial platform and to initiate therapy within 14 days of enrollment. For patients with molecularly-targeted therapies, we will describe the survival and the patient reported outcomes (PROs) and its correlation with biomarkers. We will also attempt to correlate the longitudinal brain volume changes on MRI (as a non-invasive surrogate measure of hydrocephalus) with PROs. CONCLUSIONS Considering the challenges in diagnosing and treating LMD and lack of durable treatment options, we consider that our research is pivotal to help improve the diagnosis and management of these patients and further understand disease biology, stimulating the discovery of novel therapeutics. Clinical trial information: NCT06638294.