9-ING-41 Combined With Retifanlimab, Plus Modified FOLFIRINOX for Patients With Advanced Pancreatic Adenocarcinoma (RiLEY)

Inclusion Criteria: * Is able to understand and voluntarily sign a written informed consent and is willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures. * Is aged ≥ 18 years. * Has pathologically confirmed advanced, recurrent, or metastatic pancreatic cancer AND is previously untreated with systemic agents in the advanced/metastatic setting. * Must have at least 1 measurable lesion per RECIST v1.1. Lesions that are radiated should not count as target lesions unless there is evidence of growth post radiation on a subsequent scan prior to trial enrollment. * Must have available archived FFPE tumor tissue at study entry; FFPE tissue block preferred or 10 unstained slides (metastatic tissue preferred to primary tissue) OR if FFPE archived tissue is not available, willing to provide a standard fresh tumor biopsy prior to start of study treatment for molecular profiling of the tumor using standard institutional oncomine panel. If oncomine testing has previously been completed, a repeat biopsy or testing is not required. * Has laboratory function within specified parameters (may be repeated): * Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mL; hemoglobin ≥ 8.5 g/dL, platelets ≥ 100,000/mL * Adequate liver function: transaminases (aspartate aminotransferase/ alanine aminotransferase, AST/ALT) and alkaline phosphatase ≤ 2.5 x ULN (≤ 5 X the upper limit of normal (ULN) in the setting of liver metastasis or infiltration with malignant cells); bilirubin ≤ 1.5 x ULN * Adequate renal function: CrCl \> 60 mL/min measured or calculated by Cockcroft-Gault (C-G) equation (estimated glomerular filtration rate \[eGFR\] can also be used in place of CrCl) * Serum amylase and lipase ≤ 1.5 x ULN * Eastern Co-operative Oncology Group (ECOG) performance status (PS) 0 - 1 (Appendix A) * Has received the final dose of any of the following treatments/ procedures within the specified minimum intervals before first dose of study drug: * Focal radiation therapy - 7 days * Surgery with general anesthesia - 7 days * Surgery with local anesthesia - 7 days * May have received treatment with fluorouracil or gemcitabine as a radiation sensitizer in the adjuvant setting if the treatment was received at least 6 months before study enrollment. * May have received neoadjuvant chemotherapy with FOLFIRINOX if given at least 6 months before study enrollment. * May have received prior cytotoxic doses of systemic chemotherapy in the adjuvant setting if given at least 6 months before study enrollment. * Women of childbearing potential must have a negative baseline blood or urine pregnancy test within 72 hours of first study therapy. Women may be neither breastfeeding nor intending to become pregnant during study participation and must agree to use effective contraceptive methods (hormonal AND barrier method of birth control, or true abstinence) for the duration of study participation and in the following 9 months after discontinuation of study treatment. * Male patients with partners of childbearing potential must take appropriate precautions to avoid fathering a child from screening until 9 months after discontinuation of study treatment and use appropriate barrier contraception or true abstinence. * Must not be receiving any other investigational medicinal product. Exclusion Criteria: * Is pregnant or lactating. * Is known to be hypersensitive to any of the components or metabolites of 9-ING-41 or to the excipients used in its formulation, or known sensitivity to one of the chemotherapeutic agents or to the PD-1 inhibitor. * History of receiving prior treatment with any anti-PD-1, PD-L1 or PD-L2 agent. * Has endocrine or acinar pancreatic carcinoma. * Has not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia, anemia not requiring transfusion support and infertility. Recovery is defined as ≤ Grade 1 or baseline severity per Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (v5.0). * Has significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, or stroke within 6 months of the first dose of 9-ING-41, or cardiac arrhythmia requiring medical treatment detected at screening. * Has had a myocardial infarction within 12 weeks of the first dose of 9-ING-41 or has electrocardiogram (ECG) abnormalities that are deemed medically relevant by the treating investigator or PI. * Has symptomatic rapidly progressive brain metastases or leptomeningeal involvement as assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI). Patients with stable brain metastases or leptomeningeal disease or slowly progressive disease are eligible provided that they have not required new treatments for this disease in a 28-day period before the first dose of study drug, and anticonvulsants and steroids are at a stable dose for a period of 14 days prior to the first dose of study drug. * Has had major surgery (not including placement of central lines) within 7 days prior to study entry or is planned to have major surgery during the course of the study (major surgery may be defined as any invasive operative procedure in which an extensive resection is performed, e.g., a body cavity is entered, organs are removed, or normal anatomy is altered). In general, if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges), the surgery is considered major. * Has any medical and/or social condition that, in the opinion of the investigator would preclude study participation. * Has received an investigational anti-cancer drug in the 14-day period before the first dose of study drug (or within 5 half-lives if longer) or is currently participating in another interventional clinical trial. * Has a current malignancy other than pancreatic cancer. * Known immunodeficiency syndrome or active autoimmune disease or requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (\> 10 mg/day of prednisone or equivalent). * Physiologic corticosteroid replacement therapy at doses \> 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted. * Participants with asthma that requires intermittent use of bronchodilators, inhaled steroids, or local steroid injections may participate. * Participants using topical, ocular, intra-articular, or intranasal steroids (with minimal systemic absorption) may participate. * Brief courses of corticosteroids for prophylaxis (eg, contrast dye allergy) or study treatment-related standard premedication are permitted. * Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis. * Palliative radiation therapy administered within 1 week of first dose of study treatment or radiation therapy that is \> 30 Gy within 6 months of the first dose of study treatment. Note: Participants must have recovered from all radiation-related toxicities, not require corticosteroids for this purpose, and not have had radiation pneumonitis. * Has received systemic antibiotics ≤ 7 days prior to the first dose of study drug. * History of organ transplant, including allogeneic stem cell transplantation. * Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures (eg, antihistamines and corticosteroids). * Known allergy or hypersensitivity to any component of retifanlimab or formulation components. * Has received a live vaccine within 28 days of the planned start of study drug. * Patients with known history of UGT1A1 gene polymorphism.