Neoadjuvant NIS793 in Combination with mFOLFIRINOX for the Treatment of Resectable and Borderline Resectable Pancreatic Adenocarcinoma

Inclusion Criteria

• The clinical, radiographic, and pathologic evidence support a diagnosis of pancreatic adenocarcinoma, with histology confirmatory for adenocarcinoma
• Subjects must be determined to meet the criteria for resectable or borderline resectable pancreatic cancer based on the M.D. Anderson Cancer Center (MDACC) and Alliance Intergroup Criteria classification at initial diagnosis. Patients with locally advanced or metastatic disease are not eligible for this trial
• In subjects requiring biliary decompression, biliary stent or drainage using percutaneous transhepatic cholangiogram (PTC) are allowed
• Participants must be >= 18 years of age at the time of enrollment
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin =< 1.5 x institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase) [SGPT]) =< 2.5 x institutional upper limit of normal
• Creatinine =< 1.5 x institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels above 1.5 x upper limit of normal * Creatinine clearance can be calculated per institutional standard
• Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 9 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Has locally advanced or metastatic disease as determined by CT scan or MRI
• Tumors with histologic features in addition to an adenocarcinoma component are excluded. Variant histologies include but are not limited to adenosquamous, squamous, neuroendocrine, undifferentiated with osteoclast like giant cells, acinar, hepatoid, medullary carcinomas
• Has either had any prior chemotherapy or targeted small molecule therapy, or immunotherapy or radiation therapy for pancreatic cancer * Note: If subject received major surgery for reason other than pancreatic cancer they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known prior or current synchronous malignancy, except: * Malignancy that was treated with curative intent and for which there has been no known active disease for > 5 years prior to enrollment * Curatively treated non-melanoma skin cancer, cervical cancer in situ or prostatic intraepithelial neoplasia, without evidence of prostate cancer
• Significant history of uncontrolled cardiac disease defined as uncontrolled hypertension (defined by a systolic blood pressure [BP] >= 160 mm Hg and/or diastolic BP >= 100mm Hg), unstable angina, myocardial infarction within the last 4 months, or uncontrolled congestive heart failure. Subjects with a history of cardiac disease should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better
• Has a medical history or current diagnosis of myocarditis
• Has a left ventricular ejection fraction < 50%, cardiac valvulopathy > grade 2, or elevated cardiac enzymes (troponin I) elevation > 2 x upper limit of normal (ULN)
• Has a condition/s that are considered to have a high risk of clinically significant gastrointestinal (GI) bleed or any other condition associated with or history of significant bleeding
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients receiving physiological replacement doses of corticosteroids (10mg of prednisone or equivalent) are allowed
• Has known active, uncontrolled human immunodeficiency virus (HIV) (high viral load), hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) * Patients who have been vaccinated for hepatitis B and do not have a history of infection are eligible
• Has received a live vaccine within 30 days prior to the first dose of trial treatment. Coronavirus disease of 2019 (COVID-19) vaccination or booster is permitted any time prior to enrollment or during treatment on trial, in a manner consistent with individual institutional guidelines
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen’s syndrome will not be excluded from the study
• Has an active serious infection requiring systemic therapy
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Subject is unable or unwilling to participate in a study related procedure
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment