Evaluation of Efficacy and Safety of Neoadjuvant Treatment With Pamrevlumab in Combination With Chemotherapy (Either Gemcitabine Plus Nab-paclitaxel or FOLFIRINOX) in Participants With Locally Advanced, Unresectable Pancreatic Cancer

Prior treatment

• Prior chemotherapy or radiation for pancreatic cancer
• Previous (within the past 3 years) or concurrent malignancy diagnosis except non-melanoma skin cancer and in situ carcinomas (excluding in situ breast cancer)
• Major surgery within 4 weeks prior to signing informed consent form. Biliary stents are permitted.
• Exposure to another investigational drug within 28 days of first dosing visit, or 5 half-lives of the investigational drug (whichever is longer)
• Participants who have been administered a live vaccine within 4 weeks prior to the first administration of therapy
• Participants who cannot stop chronic medications that inhibit or induce cytochrome P (CYP) 2C8 or CYP3A4

Other illness

• History of allergy or hypersensitivity to human, humanized or chimeric monoclonal antibodies
• History of allergy or hypersensitivity to any of the chemotherapy agents being prescribed or their excipients
• Any medical or surgical condition that may place the participant at increased risk while on study
• Any condition potentially decreasing compliance to study procedures
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active systemic infections, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Documented history of drug or alcohol abuse within 6 months of signing informed consent
• Any medical condition that, in the opinion of the investigator, may pose a safety risk to a participant in this trial, may confound the assessment of safety and efficacy, or may interfere with study participation
• Participants with a history of interstitial pulmonary disease, hepatitis C virus (HCV), hepatitis B virus (HBV) or human immunodeficiency virus (HIV) infection
• Participants with 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

• Understand and sign informed consent; be willing to comply with study procedures, including surgery
• Age ≥ 18 years
• Be a male, or non-pregnant and non-lactating female
• Negative serum B-hCG pregnancy test at screening for women of childbearing potential
• Male participants with partners of childbearing potential and female participants of childbearing potential are required to use highly effective contraception methods during the conduct of the study and for 6 months after the last dose of study drug
• Histologically or cytologically proven diagnosis of pancreatic ductal adenocarcinoma (PDAC)
• Locally advanced pancreatic cancer considered unresectable according to NCCN Guidelines® Version 2.2018 as determined by central imaging
• Measurable disease as defined by RECIST 1.1 criteria as determined by central imaging
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2.5 x upper limit of normal (ULN), alkaline phosphatase \<2.5 x ULN, and bilirubin ≤1.5 x ULN or in participants with biliary stenting ≤2.0 x ULN
• Adequate bone marrow function: platelets \>100,000 cells/mm3, hemoglobin \>9.0 g/dl and absolute neutrophil count (ANC) \>1,500 cells/mm3
• Adequate renal function: creatinine \< 1.5 x ULN, creatinine clearance ≥ 30 mL/min
• Less than grade 2 pre-existing peripheral neuropathy (per CTCAE)