Study of CRS-207, Pembrolizumab, Ipilimumab, and Tadalafil in Metastatic Pancreatic Cancer

Inclusion Criteria: * Age ≥18 years. * Have histologically or cytologically proven adenocarcinoma of the pancreas. * Have previously treated metastatic disease. * Have radiographic disease progression. * Patients with the presence of at least one measurable tumor lesion. * Patient's acceptance to have a tumor biopsy at baseline and on * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Patients must have adequate organ and marrow function defined by study-specified laboratory tests. * For both Women and Men, must use acceptable form of birth control while on study. * Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: * Known history or evidence of brain metastases. * Had chemotherapy, radiation, or biological cancer therapy within the last 14 days. * Have received an investigational agent or device within the last 28 days. * Had surgery within the last 28 days. * Expected to require any other form of systemic or localized cancer therapy while on study. * Have received a vaccine within the last 14 days (7 days for the COVID vaccine) or received a live vaccine within the last 30 days. * Have received steroids within the last 14 days. * Use more than 4 g/day of acetaminophen. * Use of organic nitrates. * Use of guanylate cyclase (GC) stimulators such as riociguat. * Consumption of substantial amounts of alcohol (≥5 units/day) * Use of strong or moderate cytochrome P450 3A4 (CYP3A4) inhibitor or inducer. * Patients on immunosuppressive agents within the last 7 days * Known allergy to both penicillin and sulfa. * Severe hypersensitivity reaction to any monoclonal antibody. * History of severe hypersensitivity to tadalafil. * Have implant(s) or device(s) that has not and cannot be easily removed. * Have artificial joints or implanted medical devices that cannot be easily removed. * Have any evidence of clinical or radiographic ascites. * Have significant and/or malignant pleural effusion * Uncontrolled intercurrent illness. * Subjects with active, known or suspected autoimmune disease. * Have a tissue or organ allograft, including corneal allograft. * Have been diagnosed HIV, Hepatitis B or C positive. * Is on supplemental home oxygen. * Has an unhealed surgical wound or ulcer, or a bone fracture considered non-healing. * Has clinically significant heart disease * Prior history of non-arterial ischemic optic retinopathy. * History of significant hypotensive episode requiring hospitalization within 6 months. * Has insufficient peripheral vein access. * Is unwilling or unable to follow the study schedule for any reason. * Is pregnant or breastfeeding.