The outcome of pancreatic cancer is extremely poor. NCCN guidelines recommend FOLFIRINOX or modified-FOLFIRINOX as the first-line chemotherapeutic regimen, but the response rate is unacceptably low. PD-1 blockade has been developed to a new class of cancer immunotherapy that could restore an adequate immunosurveillance against the neoplasm and enhance T-cell-mediated anticancer immune responses. Manganese has been confirmed to activate antigen-presenting cells and function as mucosal immunoadjuvants in pre-clinical studies. This one-arm, phase I/II study is designed to assess the safety and efficacy of Manganese primed combined therapy of anti-PD-1 antibody and chemotherapy.

Inclusion Criteria:

1. Subjects must have histologically proven local advanced/metastatic pancreatic cancer
2. ≥ 18 years old.
3. Life expectancy of at least 6 months.
4. Eastern Cooperative Oncology Group performance status 0-2.
5. Subjects must have at least one measurable lesion ≥ 1 cm as defined by response criteria.
6. Subjects with Anti-PD-1 antibody treatment history are eligible which must be resistance.
7. Adequate organ function.
8. Participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.

Exclusion Criteria:

1. Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
2. Serious uncontrolled medical disorders or active infections, pulmonary infection especially.
3. Prior organ allograft.
4. Women who are pregnant or breastfeeding.
5. Women with a positive pregnancy test on enrollment or prior to investigational product administration.
6. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.