NALIRIFOX+Adebrelimab+PULSAR for Advanced Pancreatic Cancer

Inclusion criteria

• Age: 18-75 years, regardless of gender.
• Histologically confirmed pancreatic ductal adenocarcinoma (PDAC).
• Previously untreated, locally advanced unresectable or metastatic PDAC, with at least one measurable lesion (RECIST v1.1) not previously irradiated.
• ECOG Performance Status (PS): 0-1.
• Expected survival ≥ 3 months.
• Willing and able to comply with study procedures, treatment, and follow-up.
• No contraindications to radiotherapy.
• Adequate organ function: WBC ≥ 2.5×10⁹/L, ANC ≥ 1.5×10⁹/L; Platelets ≥ 75×10⁹/L; Hemoglobin (HGB) ≥ 90 g/L (no transfusion or EPO dependence within 7 days); Total bilirubin (Tbil) ≤ 1.5×ULN; ALT/AST ≤ 5×ULN;Albumin ≥ 30 g/L; INR ≤ 1.5×ULN; Serum creatinine (Cr) ≤ 1.5×ULN Urine protein ≤ 1+
• HBsAg-positive patients must have HBV-DNA ≤ 1×10³ IU/mL (copies/mL). If HBV-DNA ≥ 1×10³ IU/mL, patients may still be eligible if chronic HBV is stable and not expected to increase risk, per investigator assessment.
• Voluntary participation with signed informed consent form.

Exclusion criteria

• History of severe hypersensitivity to chimeric, human(ized) antibodies, or fusion proteins.
• Pregnant or breastfeeding women, or men/women of childbearing potential unwilling/unable to use effective contraception during the study.
• Other malignancies within 5 years, except: Malignancies treated with curative intent and no known active disease for ≥5 years with low recurrence risk; Adequately treated non-melanoma skin cancer or lentigo maligna without disease evidence; Adequately treated carcinoma in situ (e.g., cervical, breast) with no current disease.
• Symptomatic moderate/severe pleural effusion or ascites.
• Active bleeding or coagulopathy (PT \>16s, APTT \>43s, INR \>1.5×ULN), bleeding tendency, or current use of thrombolytics/anticoagulants/antiplatelets.
• GI bleeding within 6 months or high bleeding risk (e.g., active ulcer with occult blood++). If occult blood+ persists, endoscopy required.
• High-risk esophageal/gastric varices needing intervention.
• History of drug abuse, psychiatric disorder, or inability to abstain.
• Solid organ/bone marrow transplant, or active autoimmune disease requiring systemic treatment within 2 years.
• Immunodeficiency or HIV infection.
• Objective evidence of pulmonary fibrosis, interstitial lung disease, pneumoconiosis, radiation-/drug-induced pneumonitis, or severely impaired pulmonary function.
• Major surgery within 4 weeks or minor surgery within 1 week (e.g., tooth extraction).
• Vaccination within 30 days before the first dose.
• Abdominal fistula, GI perforation, or abscess within 4 weeks.
• Any clinically significant abnormality affecting safety per investigator, including: Active infection requiring systemic therapy; Uncontrolled diabetes/hypertension (BP \>140/90 mmHg despite ≤2 antihypertensives); Myocardial infarction within 6 months; Thyroid dysfunction (\>NCI CTCAE v4.0 Grade 1).
• Other conditions deemed ineligible by the investigator.