Abstract A056: Therapeutic Evaluation of Brigimadlin and Anti-PD-1 in a PBMC-Co-culture Model of Patient-Derived Liposarcoma Organoids

Abstract Liposarcoma is a rare and aggressive soft tissue sarcoma subtype that often exhibits limited responsiveness to immune checkpoint inhibitors due to low tumor immunogenicity and frequent MDM2 amplification. Brigimadlin (BI 907828), a potent MDM2 inhibitor, has shown promising activity in clinical trials, particularly in patients in liposarcoma. Yet, its combination with immune checkpoint blockade remains unexplored. To assess the potential synergy between MDM2 and PD-1 pathway inhibition, we established a gelatin-based co-culture model using patient-derived tumor organoids (PDTOs) from liposarcoma patients and allogenic peripheral blood mononuclear cells (PBMCs). PBMCs were pre-activated under T cell-stimulating conditions and co-cultured with PDTOs at optimized effector-to-target (E:T) ratios. Treatment groups included vehicle control, Brigimadlin alone, anti-PD-1 antibody (Durvalumab) alone, and the combination therapy. Drug efficacy was evaluated using morphology analysis, cell viability assays, and immunohistochemistry (IHC) was performed to assess drug response. This co-culture model provides a clinically relevant platform for evaluating immunotherapeutic combinations and enables the establishment of a personalized cancer model. By facilitating patient-specific drug screening, this approach has the potential to minimize the burden of ineffective treatments in liposarcoma patients. Citation Format: Eunyoung Tak, Jeong Kim, Kyuyoung Han. Therapeutic Evaluation of Brigimadlin and Anti-PD-1 in a PBMC-Co-culture Model of Patient-Derived Liposarcoma Organoids [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr A056.