Maintenance Niraparib Plus Ipilimumab in Patients With Metastatic Pancreatic Adenocarcinoma Whose Disease Has Not Progressed on Platinum-Based Chemotherapy

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinomawith metastatic disease

• ≥18 years of age

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

• Participants must have received 8-12 cycles (4-6 months) of first-line FOLFIRINOX ormodified FOLFIRINOX for metastatic disease with stable disease or better. Patientstreated with liposomal irinotecan with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) are also eligible. Patients who were initially treated with FOLFIRINOXor NALIRIFOX but stopped oxaliplatin because of toxicity are eligible for the trial.

• Note: This requires at least stable imaging and a stable or decreasing tumormarker as applicable and as determined by the investigator.

• Measurable disease is not a requirement for study entry.

• Note: The study will require that at least 80% of enrolled patients (ie 55 ofall patients) are biopsiable at enrollment. The investigators may requiremeasurable/biopsiable disease as the study progresses in order to achieve thisgoal.

• Participants must be willing to undergo a pre-treatment fresh tumor biopsy (ifmedically feasible).

• Participants must be willing to undergo an on-treatment tumor biopsy (if medicallyfeasible).

• 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 (females)or 30 days (males) after the last dose of study treatment, or is of nonchildbearingpotential.

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

• 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) ≤2.5 xupper limit 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.

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

Exclusion Criteria:

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

• Patients who have demonstrated resistance to FOLFIRINOX are not eligible toparticipate in this study

• Patients with known pathogenic/likely pathogenic germline or somatic alteration(s)in BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.

• Patients with known mismatch repair deficiency or microsatellite instability-highcancer.

• 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

• Patients with uncontrolled hypertension, defined as systolic BP >140mmHg and/ordiastolic BP >90mmHg

• Patients with a prior history of posterior reversible encephalopathy syndrome (PRES)

• Acute infection requiring intravenous antibiotics, intravenous antiviral orintravenous antifungal agents during the 14 days prior to first dose of studytherapy

• Patients will be excluded if they have a history of or active autoimmune disease,defined as: patients with a history of inflammatory bowel disease are excluded fromthis study, as are patients with a history of symptomatic autoimmune disease (e.g.rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupuserythematosus, autoimmune vasculitis e.g. Wegener's Granulomatosis); motorneuropathy 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 requiringhormone replacement, psoriasis not requiring systemic treatment, or conditionsnot expected to recur in the absence of an external trigger.

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

• 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 andare allowed; however intranasal influenza vaccines (e.g. Flu-Mist®) are liveattenuated vaccines and are not allowed.

• 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.

• 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.

• 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.

• 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.

• 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.

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

• 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.

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

• Patients must not be simultaneously enrolled in any therapeutic clinical trial

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

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

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

• Patients must not be undergoing treatment for a second active cancer at the time ofrandomization. Exceptions include: (1) local therapies for skin cancers, (2)hormonal therapies for breast or prostate cancer without evidence of active disease.Patients may have a history of: (1) adequately treated nonmelanoma skin cancers, (2)curatively treated in situ cancer of the cervix, (3) curatively treated DCIS, (4)curatively treated stage I, grade 1 endometrial carcinoma, (5) other solid tumorsand lymphomas (without bone marrow involvement) diagnosed at least five years priorto randomization and treated with no evidence of disease recurrence.

• Patients with active hepatitis B or hepatitis C infections, as defined by positivePCR testing, may not enroll.

• Patients with HIV may enroll, but must have an undetectable viral load at the timeof enrollment and must be receiving a stable regimen of HAART.

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