P12.04.A PERSONALIZED TARGETED GLIOBLASTOMA THERAPIES BY EX VIVO DRUG SCREENING: ADVANCED BRAIN TUMOR THERAPY CLINICAL TRIAL (ATTRACT)

Abstract BACKGROUND When applied within a personalized treatment framework, targeted therapies have revolutionized the management of several solid cancers. So far, various clinical trials aiming to introduce the concept of personalized targeted therapies in glioblastoma have not been successful, as no clinically meaningful responses have been observed. Importantly, most clinical trials investigating molecular targeted therapies included all-comers and concentrated on genetic biomarkers predicting treatment response. Given the biological complexity of glioblastoma, genetic biomarkers alone are insufficient predictors of response in a given patient, and multidimensional personalized treatment approaches are warranted. As novel approaches are urgently needed, we designed a prospective clinical trial to investigate the potential of cultivated patient-derived tumor cells (PDCs) for ex vivo drug screening. MATERIAL AND METHODS In this randomized phase 2 study, we are testing the ability of PDC-based ex vivo drug screening to formulate a personalized recommendation for maintenance treatment in patients with newly diagnosed glioblastoma with unmethylated MGMT promoter after neurosurgical resection followed by combined radio-chemotherapy. Based on overall survival as the primary endpoint, we plan to include 240 patients (120 per group) to show with a power of 80% that we can increase the median survival from 12 to 17 months (hazard ratio 0.7). Patients are randomized 1: 1 to either the standard group (no drug screening) or the intervention group (drug screening and personalized recommendation for maintenance treatment). In the intervention group, automated drug screening is performed on PDCs with 28 drugs approved for the treatment of extracranial solid tumors and hematological malignancies. Based on the cytotoxic/cytostatic activity of these drugs, as quantified by relative viability based on adenosine triphosphate levels, a molecular tumor board recommends a personalized treatment regimen. RESULTS The first patient was enrolled in July 2024. Interim analysis of the ATTRACT study (NCT06512311) is expected in late 2027, and final results in 2030. The clinical trial is accompanied by a comprehensive translational research program that seeks to gain insights into the biological underpinnings of treatment response in glioblastoma. CONCLUSION If successful, functional precision oncology using PDCs in the ATTRACT trial might offer better treatment options for patients with glioblastoma, thereby breaking the long-lasting trend of unsuccessful approaches in the treatment of this tumor entity.