Niraparib + Ipilimumab or Nivolumab in Progression Free Pancreatic Adenocarcinoma After Platinum-Based Chemotherapy

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinomawith locally advanced or metastatic disease

2. ≥18 years of age

3. Patients must be able to understand the study procedures and agree to participate inthe study by providing written informed consent

4. Patients must have received treatment with platinum-based (cisplatin, oxaliplatin orcarboplatin) treatment for locally advanced or metastatic pancreatic cancer and havereceived a minimum of 16 weeks of therapy without evidence of disease progressionbased on the investigator's opinion. This does not have to be the patient's currenttreatment.

• This requires at least stable imaging and a stable or decreasing tumor markeras applicable and as determined by the investigator.

• If a patient has demonstrated a biochemical and imaging response to platinumtherapy and has not progressed within 16 weeks of starting this therapy but hadto discontinue platinum prior to 16 weeks for a legitimate medical reason (asdetermined by the investigator), the patient may still be considered for thetrial

5. Patients may have previously failed non-platinum containing therapy or may neverhave previously progressed on treatment

• Discontinuation of the platinum component of the regimen forchemotherapy-related toxicity is permissible provided the patient haspreviously received at least 16 weeks of platinum-based therapy withoutevidence of disease progression ≤8 weeks after treatment with the platinumagent

6. Measurable disease is not a requirement for study entry

7. Female participant has a negative serum pregnancy test within 24 hours prior totaking study treatment if of childbearing potential and agrees to abstain fromactivities that could result in pregnancy from screening through 6 months after thelast dose of study treatment, or is of nonchildbearing potential

8. Male patient agrees to use an adequate method of contraception starting with thefirst dose through 90 days after the last dose of study treatment

9. Adequate organ function confirmed by the following laboratory values obtained ≤7days prior to the first day of study therapy:

• Absolute neutrophil count (ANC) ≥1.5 x 109/L

• Platelets>100 x 109/L

• Hemoglobin ≥9g/dL

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x upperlimit of normal (ULN); if liver metastases, then ≤5 x ULN

• Total bilirubin ≤1.5 x ULN; if liver metastases or metabolic disorder such asGilbert's syndrome, then ≤2.5 x ULN.

• Serum creatinine ≤1.5 x ULN or estimated glomerular filtration rate (GFR) ≥45mL/min using Cockcroft Gault formula.

10. Eastern Cooperative Oncology (ECOG) performance status of 0 to 1.

Exclusion Criteria:

1. Prior treatment with a PARP inhibitor, ipilimumab, nivolumab or other cytotoxicT-lymphocyte-associated protein (CTLA-4), PD-1 or PD-L1 inhibitor.

2. Patients who have demonstrated resistance to platinum agents (e.g. oxaliplatin,cisplatin) are not eligible to participate in this study

3. Clinical evidence of uncontrolled malabsorption and/or any other gastrointestinaldisorder or defect that would, in the opinion of the investigator, interfere withthe absorption of niraparib

4. Acute infection requiring intravenous antibiotics, antiviral or antifungal agentsduring the 14 days prior to first dose of study therapy

5. Patients will be excluded if they have an active, known or suspected autoimmunedisease, defined as: patients with a history of inflammatory bowel disease areexcluded from this study, as are patients with a history of symptomatic autoimmunedisease (e.g. rheumatoid arthritis, systemic progressive sclerosis (scleroderma),systemic lupus erythematosus, autoimmune vasculitis e.g. Wegener's Granulomatosis);motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome). NOTE: Patients are permitted to enroll if they have vitiligo, type I diabetesmellitus, residual hypothyroidism due to autoimmune condition only requiring hormonereplacement, psoriasis not requiring systemic treatment, or conditions not expectedto recur in the absence of an external trigger.

6. Has a history of interstitial lung disease or active, non-infectious pneumonitis

7. Has received a live vaccine within 4 weeks prior to the first dose of trial therapy (Note: seasonal influenza vaccines for injection are generally inactivated and areallowed; however intranasal influenza vaccines (e.g. Flu-Mist) are live attenuatedvaccines and are not allowed

8. For fertile patient (female able to become pregnant or male able to father a child),refusal to use effective contraception during the period of the trial and:

• Female patients refusing to use effective contraception for 6 months after thelast dose of study drug.

• Male patients refusing to use effective contraception for 90 days after thelast dose of study drug.

9. Received any systemic treatment for pancreatic cancer ≤14 days prior to first doseof therapy. Patients must not have had investigational therapy administered ≤4weeks, or within a time interval less than at least 5 half-lives of theinvestigational agent, whichever is longer, prior to the first scheduled day ofdosing in this study

10. Patients will be excluded if they have a condition requiring systemic treatment witheither corticosteroids (>10mg daily prednisone equivalents) or otherimmunosuppressive medications within 14 days of study drug administration. Inhaledor topical steroids and adrenal replacement doses >10mg daily prednisone equivalentsare permitted in the absence of active autoimmune disease.

11. Patient has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia dueto prior chemotherapy that persisted > 4 weeks and was related to the most recenttreatment.

12. Non-study related minor surgical procedure ≤5 days, or major surgical procedure ≤21days, prior to the first dose of therapy; in all cases, patients must besufficiently recovered and stable before treatment administration.

13. Active drug or alcohol use or dependence that would interfere with study compliance.

14. Presence of any other condition that may increase the risk associated with studyparticipation or may interfere with the interpretation of study results, and, in theopinion of the investigator, would make the patient inappropriate for entry into thestudy.

15. Patient must not have any known history of myelodysplastic syndrome (MDS) or acutemyeloid leukemia (AML)

16. Patients must not be simultaneously enrolled in any therapeutic clinical trial

17. Patients must not have had radiotherapy within 4 weeks of the first dose of studytreatment

18. Patients must not have a known hypersensitivity to the components of niraparib orthe excipients

19. Patients must not have received a transfusion (platelets or red blood cells) ≤ 4weeks of the first dose of study treatment

20. Patients must not be undergoing treatment for an active cancer at the time ofrandomization. Exceptions include: local therapies for skin cancers and hormonaltherapies for breast or prostate cancer.

21. Patients must not have a history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS), and must not test positivefor HIV during study screening.

22. Patients must not have known, symptomatic brain or leptomeningeal metastases