This clinical trial, sponsored by Memorial Sloan Kettering Cancer Center, investigates the efficacy of NALIRIFOX combined with ablative dose radiation therapy (AD-XRT) and capecitabine as a total neoadjuvant therapy for patients with borderline resectable and locally advanced PDAC. The study aims to assess treatment response, quality of life, and event-free survival in a single-arm design with an estimated enrollment of 60 participants.