The purpose of this study is to evaluate the safety and clinical activity of maintenance olaparib and pembrolizumab following multi-agent, low dose chemotherapy with gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan (GAX-CI) in patients with untreated metastatic pancreatic ductal cancer.

Inclusion Criteria:

• Cohort 1 - Subject has stable disease as measured by RECIST 1.1 or iRECIST after 6 cycles of GAX-CI.
• Cohort 2 - Subject has progressive disease as measured by RECIST 1.1 and iRECIST prior to 6 cycles of GAX-CI.
• 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.
• Woman 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.

Exclusion Criteria:

• 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.
• Has history of central nervous system (CNS) metastases and/or carcinomatous meningitis.
• 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.
• Hypersensitivity reaction to any monoclonal antibody.
• Is taking a moderate or strong CYP3A inhibitor.
• Has uncontrolled acute or chronic medical illness.
• Has known additional malignancy that is progressing and requires active treatment.
• 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 active autoimmune disease.
• 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 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.
• Requirement for daily supplemental oxygen.
• Patients with a history of (non-infectious) pneumonitis/interstitial lung disease that requires steroids.
• Subject with clinically significant wound.
• Has a confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
• 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.
• Unwilling to have blood drawn.
• Has known psychiatric or substance use disorder that would interfere with cooperation with the requirements of the trial.
• Woman who are pregnant or breastfeeding.