Multi-agent Low Dose Chemotherapy GAX-CI Followed by Olaparib and Pembro in Metastatic Pancreatic Ductal Cancer.

Prior treatment

• Patients who will be considered for surgery are ineligible.
• Had chemotherapy within 5 years prior to study treatment.
• Have received any investigational drugs within 28 days prior to study treatment.
• Had surgery within 28 days of dosing of investigational agent.
• Require any antineoplastic therapy.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent.
• Has received prior therapy with gemcitabine, nab-paclitaxel, capecitabine, cisplatin, irinotecan, or PARP inhibitor.
• Is taking a moderate or strong CYP3A inhibitor.
• Has received radiotherapy for pancreatic cancer.
• Have received any live vaccine or live-attenuated, any allergen hyposensitization therapy, growth factors or major surgery within 30 days prior to study treatment.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Has an active known or suspected autoimmune disease or is receiving chronic systemic steroid therapy within 7 days prior to the first dose of study drug.
• Prior tissue or organ allograft or allogeneic bone marrow transplantation.
• Has a confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.

Other illness

• Has history of central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Hypersensitivity reaction to any monoclonal antibody.
• Has uncontrolled acute or chronic medical illness.
• Has known additional malignancy that is progressing and requires active treatment.
• Has active autoimmune disease.
• Patients with a history of (non-infectious) pneumonitis/interstitial lung disease that requires steroids.
• Infection with HIV.
• Has active Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or Hepatitis C virus (defined as hepatitis C virus (HCV) RNA \[qualitative\] is detected) infection. Patients who are Hepatitis C antibody positive and viral load negative will be permitted to enroll.
• Has uncontrolled infection.
• Has known psychiatric or substance use disorder that would interfere with cooperation with the requirements of the trial.

Lab values

• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Other

• Requirement for daily supplemental oxygen.
• Subject with clinically significant wound.
• Unwilling to have blood drawn.
• Women who are pregnant or breastfeeding.

• Ability to understand and willingness to sign a written informed consent document.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Have metastatic histologically or cytologically-proven ductal pancreatic cancer.
• Patients must not have received prior treatment for pancreatic cancer.
• Have measurable disease based on RECIST 1.1.
• Willing to have to a tumor biopsy.
• Patients must have adequate organ and marrow function defined by study - specified laboratory tests.
• Women of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.
• Men must use acceptable form of birth control while on study.
• Participant understands the study regimen, its requirements, risks and discomforts, competent to report AE, understand the drug dosing schedule and use of medications to control AE.