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

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.