Abstract B024: Advancing precision medicine: A prospective feasibility study integrating <i>ex vivo</i> drug testing and genomic profiling to improve outcomes in children and adults with advanced cancers

Abstract Background: Despite advancements in precision oncology, only a minor subset of patients can be matched with effective targeted therapy, and even fewer experience sustained benefits. This is partly because current approaches, such as genomic profiling alone, do not fully capture the complexity of tumor biology. Integrating ex vivo drug sensitivity testing of patient-derived tumor cells with genomic profiling may offer a more comprehensive solution, helping identify effective treatments for patients with limited standard options or failed therapies. Objective: This prospective, non-randomized, single-arm observational study aims to evaluate the feasibility and clinical utility of integrating ex vivo drug sensitivity testing with genomic profiling to support real-time treatment decision-making for pediatric and adult patients with advanced solid tumors. The primary objective is to determine if treatment recommendations based on ex vivo drug testing can be delivered within a clinically actionable timeframe. The secondary objective is to evaluate if these patient-derived organoids (PDO)-guided recommendations improve clinical outcomes, specifically progression-free survival (PFS) and overall survival (OS). Methods: Tumor biopsies or resection specimens from patients with advanced solid tumors undergoing genomic profiling (matched tumor-normal WGS, total RNAseq) at our center will be processed to establish PDOs. Drug sensitivity will be tested using a luminescence-based viability assay (CellTiterGlo). Drug panels will be tailored for each patient by including on- and off-label options relevant to each diagnosis. If possible, drugs in clinical trials will also be included. Patients lacking effective standard-of-care treatments will receive alternative recommendations informed by both PDO drug sensitivity profiles and genomic data. Feasibility will be assessed by tracking the time required to return actionable recommendations to the clinical team within a predefined window (&amp;lt;4 weeks). For patients with resistant tumors, transcriptomic profiling will be used to explore the molecular mechanisms underlying resistance and potential alternative therapies. Approximately 30 patients will be enrolled over two years for an initial assessment of the clinical impact of this approach. Currently, we are performing a pilot study to optimize tissue processing and drug screening protocols across various tumor types, correlating ex vivo drug response with patient treatment outcomes. Conclusion: We hypothesize that PDO-guided treatment will lead to improved clinical outcomes compared to those treated without ex vivo guidance. This study will provide foundational evidence for integrating functional precision oncology into clinical practice and support future large-scale trials that could enhance the standard of care for patients with advanced and treatment-resistant cancers. Citation Format: Malene Blond, Maria E Skjøtt, Aram Arshadi, Søren B Poulsen, Ronja Carstensen, Kirstine J Elbæk, Anders R Korshøj, Britt E Laursen, Eva A Sædder, Ole H Larsen, Torben Mikkelsen, Kasper Thorsen, Martin K Thomsen, Maria Rusan. Advancing precision medicine: A prospective feasibility study integrating ex vivo drug testing and genomic profiling to improve outcomes in children and adults with advanced cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr B024.