Inclusion Criteria:
1. Age from 18 to 79 years
2. Able to understand and sign informed consent
3. Histologically or cytologically proven diagnosis of pancreatic ductal adenocarcinoma
4. Locally advanced pancreatic cancer considered unresectable according to NCCN Guidelines® Version 2.2021
5. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors RECIST 1.1 criteria
6. Male, or non-pregnant and non-lactating female
7. Women patients of childbearing potential\* must have a negative serum/urine pregnancy test at screening and baseline, and be willing to use a highly effective\*\* contraception. The patient should be advised to continue the contraception for at least 6 months following the completion of dosing. Women with cessation for \> 24 months of previously occurring menses, or women of any age who have had a hysterectomy, or have had both ovaries removed will be considered to be of non-childbearing potential
8. Male patients of reproductive potential must be willing to use one acceptable method of contraception, as judged by Investigator and Sponsor and/or to refrain from donating sperm from the time of screening through at least 6 months following the completion of dose administration
9. No prior systemic therapy, radiation therapy, or resection for pancreatic cancer
10. Life expectancy ≥ 12 weeks
11. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
12. Adequate liver function:
1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 x upper limit of normal (ULN),
2. Bilirubin ≤ 1.5 x ULN or in subjects with biliary stenting ≤ 2.0 x ULN
3. Alkaline phosphatase \< 2.5 x ULN
4. Subjects with biliary stenting do not need to wait for their alkaline phosphatase to become \< 2.5 x ULN if their total bilirubin, AST and ALT have improved to within required study levels with criteria 12a and 12b
13. Adequate bone marrow function: platelets \>100,000 cells/mm3, hemoglobin \> 9.0 g/dl and absolute neutrophil count (ANC) \>1,500 cells/mm3
14. Adequate renal function: creatinine \< 1.5 x ULN, creatinine clearance ≥ 30 mL/min/m2
15. Adequate nutritional state with Albumin ≥ 2.5 g/dL
16. Less than grade 2 pre-existing peripheral neuropathy (per CTCAE)
17. Patients covered by Health Insurance System
Exclusion Criteria:
1. Patients with resectable pancreatic cancer
2. Evidence of the presence of metastases.
3. Patients who have received prior systemic therapy, radiation therapy, or resection for pancreatic cancer or prior therapy with NP137
4. Patients with known Dihydropyrimidine dehydrogenase (DPD) deficiency, or homozygosity for UGT1A1\*28 polymorphism (UGT1A1 genotype analysis is not required to be eligible)
5. Previous (within the past 3 years) or concurrent malignancy diagnosis except non-melanoma skin cancer and in situ carcinomas (excluding in situ breast cancer)
6. History of severe (grade ≥ 3) allergic reactions to one of the components of chemotherapy, or NP137
7. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, may decrease subject's compliance to study's procedures or may render the patient at high risk from treatment complications in the opinion of the treating investigator
8. Subjects with known poorly controlled comorbid conditions, including; congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), uncontrolled diabetes mellitus (DM) or neurologic disorders (not acutely related to pancreatic cancer) or limited function
9. Major surgery within 4 weeks prior to signing informed consent form. Biliary stents are permitted
10. History of allergy or hypersensitivity to human, humanized or chimeric monoclonal antibodies
11. History of allergy or hypersensitivity to any of the chemotherapy agents belonging to mFOLFIRINOX regimen
12. Subjects with a history of chronic HCV, HBV or HIV infection
13. Subjects who have been administered a live vaccine within four weeks prior to the first administration of therapy
14. Subjects who cannot stop chronic medications that inhibit or induce CYP2C8 or CYP3A4
15. Persons referred to in Articles L1121-5 to L1121-8 of the French code of public health (this corresponds to all persons protected: pregnant or parturient women, breastfeeding mothers, persons deprived of liberty by judicial or administrative decision, persons subject to a legal protection measure)
16. Patients who have active infection requiring systemic therapy (other than HCV, HBV, HIV).
17. Patients who participate or plan to participate in another interventional clinical trial or who is in exclusion period for another study.
