Background: There is increasing evidence suggesting benefit from a neoadjuvant approach to PC. However, the optimal regimen is unclear and will likely require a precision medicine approach, where patient and tumor attributes define therapy. Platinum-containing regimens have shown survival benefit for PC, with occasional exceptional responders, but biomarkers (BM) of response are not well defined and treatment decisions are often based on patient performance status (PS) and co-morbidity. Tumors with defects in BRCA1/2and other Fanconi Anemia genes show defective DNA damage response (DDR), conferring potential selective sensitivity to DNA-damaging agents (e.g. platinum) and newer targeted agents. We have shown that DDR deficiency (DDRd) is present in up to 20% of PC. This study aims to exploit DDRd as a therapeutic vulnerability, with integrated analysis to define candidate BM for FA and AG response. Methods: PRIMUS-002 will enroll patients registered on the Precision-Panc Master Protocol who are molecularly profiled using the Precision-Panc Clinical Cancer Genome including a novel DDRd assay, and the transcriptome with longitudinal sampling (pre-, during, and post-treatment). Patients receive either FA (nab-paclitaxel 150mg/m²IV,oxaliplatin 85mg/m², folinic acid 350mg flat dose, fluorouracil infusion 2400mg/m²continuous IV infusion), orAG (nab-paclitaxel 125mg/m², gemcitabine 1000 mg/m²) for 3 months,based on patient age and PS.Following initial safety analysis, chemoradiation may be introduced. The primary endpoint is disease progression (DP) during neoadjuvant therapy. The study is designed to detect a 20% difference in DP between the BM+ve (10%) and BM –ve (30%) in patients treated with FA (90% power, 5% 1-sided level of statistical significance)., Exploratory translational endpoints include surrogate therapeutic response assessment using CA19.9, PET-CT SUV, DWI-MRI and ctDNA. Current Enrolment: 2 patients enrolled to date: 1 to receive FA and 1 to AG treatment. Clinical trial information: ISRCTN34129115.