This is an single-center, prospective, open-label clinical trial, to explore the safty and efficacy of combination of Bortezomib, Sindilizumab, and mFOLFIRINOX Chemotherapy (oxaliplatin, fluorouracil, irinotecan, leucovorin) in metastatic pancreatic cancer

Phase 1 (Evaluation of Drug Tolerance) Primary objective: To evaluate the tolerability of bortezomib, PD-1 mAb and mFOLFIRINOX in patients with advanced metastatic pancreatic cancer, and to determine the dose of bortezomib in the combination regimen; Secondary objectives: To evaluate the immunogenicity characteristics and safety of the combination regimen of bortezomib, PD-1 mAb and mFOLFIRINOX in patients with advanced metastatic pancreatic cancer; Phase 2 (Dose Expansion) Primary objective: To evaluate the tolerability and efficacy of the combination regimen of bortezomib, PD-1 mAb and mFOLFIRINOX in patients with advanced metastatic pancreatic cancer; Secondary Objective: ORR; PFS; OS; and to evaluate the immunogenicity and safety of bortezomib, PD-1 mAb and mFOLFIRINOX in subjects with advanced metastatic pancreatic cancer; and to explore biomarkers related to combination therapy.

Inclusion Criteria:

• Pathologically (histologically or cytologically) confirmed pancreatic ductal adenocarcinoma (PDAC).
• Recurrent disease or metastatic disease (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.
• Never receive any systematic treatment or Progression after fisrt line Gemcitabine base chemotherapy
• 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.
• Signed informed consent.

Exclusion Criteria:

• History of participation of other clinical trails within 4 weeks
• History of autoimmune disease or other condition receiving glucocorticoid treatment
• History of receiving chemotherapy within 2 weeks
• History of radiotherapy and molecular target therapy within 2 weeks
• History if active tuberculosis
• History of malignance treatment in the past, excluding basal and cutaneous squamous cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma
• Major cardiovascular diseases (including myocardial infarction, unstable angina, congestive heart failure, severe uncontrolled arrhythmia) during the past six months of enrollment.
• Hematological precancerous diseases, such as myelodysplastic syndromes.
• 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).
• Immune deficiency syndrome, such as active tuberculosis and HIV infection.
• Allograft requires immunosuppressive therapy or other major immunosuppressive therapies.
• Severe serious wounds, ulcers or fractures.
• Clinical evaluation is unacceptable