Using organoids to predict efficacy of adjuvant treatment to improve outcome in resectable pancreatic cancer: UNITEPANC (AIO-PAK-0424), a prospective, multicenter, proof-of-concept trial of the AIO Pancreatic Cancer Group.

TPS4266 Background: Pancreatic cancer (PDAC) is a heterogeneous disease and there is a lack of predictive biomarker to guide treatment. Patient tumor derived organoids (PDO) recapitulate key morphological and genetic features and may preserve patient-specific drug response phenotypes Methods: UNITEPANC is a prospective, proof of concept, multicenter IIT of the German AIO PDAC Group and funded by the German Cancer Aid. UNITEPANC examines the feasibility of an organoid-educated adjuvant treatment approach with respect to organoid establishment, expansion and characterization and its potential role for selecting an optimal adjuvant treatment in PDAC in a multicenter setting. Preparatory activities like harmonizing SOPs and round-robin-tests for generation of organoids and organoid-based pharmacotyping in the trial centers and the different Organoid Facilities have been completed and evaluated. UNITEPANC examines selection of adjuvant chemotherapy by pharmacotyping of tumor organoids. Options for adjuvant treatment are gemcitabine, gemcitabine/capecitabine, gemcitabine/nab-paclitaxel or mFOLFIRINOX. Major inclusion criteria are R0 or R1 resected, histologically confirmed PDAC and patients in principle, suitable for mFOLFIRINOX treatment in the adjuvant setting, postoperative Ca19-9 < 180 U/ml, and a timely PDO-based chemotherapy recommendation by the UNITEPANC Organoid Board to guarantee a start of the adjuvant treatment within 12 weeks after resection. UNITEPANC is an interventional, prospective, multicenter, single-arm trial. 92 patients shall be allocated to the trial for the generation of organoids, 38 patients shall be enrolled for PDO-based adjuvant treatment and 34 patients need to be analyzed as ITT population in the follow-up period. Efficacy: The efficacy endpoint of the trial is purely descriptive and intended to obtain a signal for further development of the strategy. This requires the proof of an efficient 1) generation and 2) expansion of PDO and 3) a clear sign that an organoid-educated treatment selection is superior to standard treatment with mFOLFIRINOX. For 1) and 2) we have chosen a rate of 75% and 60%, respectively, according to the literature. For 3): The approach would be considered promising, if the true 18-months-DFS rate is 77% (corresponding to a hazard ratio of 0.5 compared to Prodige-24, 80% power, one-sided type I error 0.1. HR-QoL data will be analyzed (QLQ-C30, Pan26). Additionally, an extensive translational program is enclosed. UNITEPANC has started recruitment in Q3/2025. Clinical trial information: 2023-510490-34-00.