Safety and Tolerance of Epigenetic and Immunomodulating Drugs Combined With Chemotherapeutics in Patients Suffering From Advanced Pancreatic Cancer

Exclusion Criteria

• •Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events from agents administered more than 4 weeks earlier
• •Patients receiving any other investigational agents.
• •Patients who have previously received Romidepsin, Azacitidine, Lenalidomide or Durvalumab or any programmed cell death-1 (PD1) or programmed cell death ligand 1 (PD-L1) inhibitor or participate currently on another clinical trial
• •Patients with untreated or uncontrolled brain metastases or leptomeningeal disease
• •Presence of other active illnesses
• •Any known cardiac abnormalities such as: congenital long QT syndrome; corrected QT interval (QTc interval) ≥ 470 milliseconds. Calculated from 3 ECGs using Fridericia's Correction
• •Myocardial infarction within 6 months prior to cycle 1, day 1 (C1D1).
• •Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
• •Symptomatic coronary artery disease (CAD)
• •Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions and/or known ejection fraction \<40% by multiple gated acquisition scan (MUGA) or \<50% by echocardiogram and/or MRI
• •A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)
• •Concomitant use of any drug known to prolong QT interval
• •Concomitant use of strong CYP3A4 inhibitors
• •Lactating, pregnant or breast feeding
• •Patients with any other medical or psychological condition deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
• •Diagnosis of immunodeficiency or any condition that requires systemic steroid therapy or other forms of immunosuppressive therapy
• •Prior thromboembolic events
• •History of other malignancies
• •Any uncontrolled active systemic infection
• •Major surgery within 4 weeks prior to first dose of study drug
• •Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
• •History of stroke or intracranial hemorrhage within 6 months prior to enrollment
• •History of interstitial lung disease, idiopathic pulmonary fibrosis, or pulmonary hypersensitivity pneumonitis
• •Unable to swallow oral medication or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction
• •Concomitant use of warfarin or other Vitamin K antagonists
• •Known allergy or hypersensitivity to any study drug or any of the study drug excipients
• •Unwilling or unable to participate in all required study evaluations and procedures. Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information.
• •Current or prior use of immunosuppressive medication within 14 days before the first dose of Durvalumab.
• •Active or prior documented autoimmune or inflammatory disorders
• •Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy
• •History of allogenic organ transplantation
• •Active infection including tuberculosis
• •Receipt of live attenuated vaccine within 30 days prior to the first dose of Investigational medicinal product (IMP)
• •Subject is an employee of the sponsor