EXPLORING PERSONALISED GLIOBLASTOMA THERAPIES THROUGH FUNCTIONAL PRECISION MEDICINE: EARLY DATA FROM PEAR-GLIO

Abstract AIMS Gliomas and other primary brain tumours remain a significant cause of cancer-related mortality, with lim- ited predictive biomarkers to guide therapy selection. The PEAR-GLIO trial investigates Pear Bio’s AI-driven ex vivo platform to evaluate the therapeutic sensitivity of FDA-approved and experimental treatments on patient- derived 3D immune-microtumours. This observational study aims to validate the platform’s ability to provide actionable insights for patient stratification and treatment optimisation. The trial also integrates patient and public involvement (PPIE) to improve study design and accessibility. METHODS PEAR-GLIO (NCT06038760) is a UK-based observational study enrolling 50 patients with operable primary brain tumours, including grades 2-4 gliomas. Inclusion criteria include histologically confirmed malignancy, avail- ability of ≥0.4g of tumour tissue and 40mL of whole blood, and consent for sample and data use. Patients re- ceiving pre-surgical chemotherapy or radiotherapy within 30 days or with inoperable disease are excluded. Tumour-derived and immune cells are co-cultured as physiologically relevant 3D immune-microtumours and exposed to FDA-approved and experimental treatments. Phenotypic and molecular responses, including changes in tumour viability, cell death, migration, and immune cell infiltration, are assessed using live imag- ing and computer vision. Real-time confocal imaging and omics analyses evaluate drug mechanisms of action, correlating responses with biomarkers like MGMT methylation, IDH mutation, and 1p/19q co-deletion. RESULTS Recruitment began in October 2023, with 12 patients enrolled to date. Data from the first cohort will guide plat- form optimization and scalability. All samples are anonymised, with outcomes monitored per RANO guidelines. CONCLUSION Early PPIE efforts have enhanced trial design. The platform is concurrently being validated in other high- unmet-need indications, including early-stage breast cancer (NCT05435352) and metastatic kidney cancer (NCT06264479), aiming to advance precision treatment selection and transform clinical oncology.