BACKGROUND: Combination of chemotherapy and immunotherapy is the current standard of care for advanced endometrial cancer. However, survival outcome remains poor, highlighting the urgent need for new treatments and reliable tools to identify patients who will benefit from them. Patient-Derived Tumor Organoids (PDTO) are three-dimensional structures established from patient tumors, and are closely mimicking the features of the tumor of origin. Moreover, more and more evidences show that PTDOs hold promises as predictive tools for the response to treatment of patients. METHOD: The PENDOR study is a monocentric observational study designed to assess the feasibility of generating and testing PDTOs derived from endometrial cancer for evaluating treatment sensitivity. PDTOS will be established from surgical specimens not required for anatomopathological diagnosis. Tumor cells will be dissociated, embedded in extracellular matrix, and cultured in a medium supplemented with growth factors and signaling pathways inhibitors. Molecular and histological analyses will be conducted to validate the resemblance of PDTO to the original tumor. Response of PDTO to conventional chemotherapy and PARP inhibitors will be evaluated and compared to clinical response and to the results of an academic HRD test Genomic Instability Scar (GIScar), respectively, to assess their predictive value. DISCUSSION: This pilot study aims to validate the feasibility to develop PDTOs from endometrial cancer from patients who will undergo surgical resection. We aim to provide a proof of concept regarding the predictive value of these models for their potential application into routine clinical practice as part of precision medicine. This approach could therefore facilitate the identification of patients who could benefit from PARP inhibitors. TRIAL REGISTRATION: This clinical trial (N°ID-RCB: 2024-A01206-41) has been validated by local research ethic committee on July 16th 2024 and registered at ClinicalTrials.gov with the identifier NCT06603506 on September 6th 2024, version 1.