The prognosis of pancreatic cancer is extremely poor. Current guidelines recommend FOLFIRINOX or modified-FOLFIRINOX as the first-line chemotherapeutic regimen. Studies have shown that immunotherapy with Anti-PD-1 antibody can effectively increase the response rate and prolong patient survival in a number of cancer diseases. Here investigators intend to compare the therapeutic effects of modified-FOLFIRINOX alone and the combination of modified-FOLFIRINOX and Anti-PD-1 antibody in patients with borderline resectable and locally advanced pancreatic cancer.

Investigators chose borderline resectable and locally advanced pancreatic cancer patients. The planned treatment was given to the participants after randomization. Response rate, event-free survival, overall survival, drugs related side effects and other endpoints events were recorded and analyzed, to assess the combination treatment with modified-FOLFIRINOX and Anti-PD-1 antibody could or couldn't benefit the patients with borderline resectable and locally advanced pancreatic cancer.

Inclusion Criteria:

• Pathologically (histologically or cytologically) confirmed pancreatic ductal adenocarcinoma (PDAC).
• No evidence of distant metastasis (such as liver, peritoneum, lung) evaluated by abdominal contrast-enhanced CT, MRI, and chest CT. PET/CT or other imaging examinations would be used if necessary.
• Initial assessment for definitive borderline resectable or locally advanced tumors (resectability judgment is based on CT enhanced scan or magnetic resonance imaging, NCCN2019 first edition standard).
• ECOG score 0 or 1.
• Serum creatinine level is normal, and serum total bilirubin level is less than 1.5 x ULN.
• ALT and AST are less than 2 x ULN.
• If biliary obstruction is observed, biliary decompression should be performed when the patient is randomly assigned to receive neoadjuvant chemotherapy.
• Leukocyte count (> 3.5 x 10^6 /mL), neutrophil count (> 1.5 x 10^6 /mL), platelet count (> 80 x 10^6 /mL), hemoglobin (> 9 g/dL).
• Signed informed consent.

Exclusion Criteria:

• History of malignance treatment in the past, excluding basal and cutaneous squamous cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma
• History of participation of other clinical trails within 4 weeks
• History of immunotherapy within 4 weeks
• History of receiving chemotherapy, radiotherapy and molecular target therapy within 2 weeks
• Tumor is a local recurrent lesion.
• Imaging confirmed severe portal hypertension / cavernous transformation.
• Ascites
• Gastric outlet obstruction
• Respiratory failure requires supplementation of oxygen.
• Immune deficiency syndrome, such as active tuberculosis and HIV infection.
• Hematological precancerous diseases, such as myelodysplastic syndromes.
• Major cardiovascular diseases (including myocardial infarction, unstable angina, congestive heart failure, severe uncontrolled arrhythmia) during the past six months of enrollment.
• Evidence of clinical-related or previous interstitial lung disease, such as noninfectious pneumonia or pulmonary fibrosis, or baseline chest CT scan or chest X-ray findings
• Previous or physical findings of central nervous system disease, except for adequately treated (e.g. primary brain tumors, uncontrolled seizures or strokes with standard medications)
• Preexisting neuropathy > 1 (NCI CTCAE).
• Allograft requires immunosuppressive therapy or other major immunosuppressive therapies.
• Severe serious wounds, ulcers or fractures.
• Confirmed coagulant disease.
• Clinical evaluation is unacceptable.