This study is a single-arm phase II clinical trial. The study targets patients aged 18-75 years with ECOG performance status 0-2, diagnosed with locally advanced pancreatic ductal adenocarcinoma based on comprehensive assessment of pathology and imaging studies (CT or MRI). Participating patients will receive the GnP regimen every 21 days (nab-paclitaxel 125mg/m² ivgtt on days 1 and 8 + gemcitabine 1000mg/m² ivgtt on days 1 and 8, repeated every 21 days) combined with serplulimab (200mg ivgtt Q3W). In the second cycle, patients will receive SBRT targeting the primary tumor and/or retroperitoneal lymph nodes: 6.6Gy×5 fractions, 7Gy×5 fractions, or 8Gy×5 fractions, administered every other day with radiotherapy completed in 5 sessions (specific selection determined by investigators based on lesion size and organs at risk \[OAR\] assessment). Comprehensive evaluation including tumor markers and CT scans will be performed every 2 cycles with multidisciplinary team (MDT) review, and patients who meet surgical criteria will undergo radical resection surgery.
Bone marrow function (no blood transfusion within 14 days prior to screening): White blood cell count (WBC) ≥4.0×10⁹/L, absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelet count (PLT) ≥80×10⁹/L, hemoglobin (Hb) ≥90 g/L;
Hepatic function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3× upper limit of normal (ULN), total bilirubin (TBIL) ≤2×ULN (for subjects with hepatic metastases: ALT and AST ≤5×ULN, TBIL ≤2×ULN), Child-Pugh score ≤7;
Renal function: Serum creatinine (Cr) ≤1.5×ULN, proteinuria ≤2+ or ≤2 g/24h, glomerular filtration rate (GFR) ≥60 mL/min/1.73 m²;
Coagulation function: Prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR) ≤1.5×ULN. Patients receiving stable anticoagulation therapy for at least 30 days prior to study drug treatment may have PT or INR >1.5×ULN if deemed appropriate for the study by investigator assessment, provided adequate justification is documented;
Known hypersensitivity or allergy to any of the study drugs;
Patients with distant metastatic disease classified as Stage IV pancreatic cancer;
Patients whose tumor lesions are determined by the surgical team or multidisciplinary team to be resectable or borderline resectable pancreatic cancer based on imaging studies (CT or MRI) (per 2022 CSCO guideline definition);
Patients whose lesions are deemed unsuitable for stereotactic body radiation therapy (SBRT) by investigator assessment;