Inclusion Criteria:
* Female subjects ≥ 18 years of age.
* Histologically confirmed progressive or recurrent endometrial cancer or ovarian cancer with previously identified ARID1A tumor mutations.
a. Any ARID1A mutation is eligible and any CLIA Next generation sequencing test is allowable for eligibility.
* Archival tumor tissue specimen available. Histological tissue specimen (tissue block or 8-10 unstained slides) must be available (specimen can be the sample at diagnosis or taken at relapse). Otherwise, patient must agree to have tumor biopsy to obtain sufficient tissue for histological assessment. If unable to be safely biopsied and patient desires enrollment, may be enrolled per MM discretion.
* A subset of patients (15 ovarian samples and 15 endometrial samples) should agree to have optional tumor biopsy for translational studies assessment. If unable to be safely biopsied and patient desires enrollment, may be enrolled per medical monitor discretion. Tissue collection for the optional translational biopsies will continue until a total of 30 viable samples have been collected (15 endometrial and 15 ovarian). Patient agrees to have blood draw at pre-treatment and post-treatment (end of study) for translational studies assessment.
* Patients who have progressed after ≥1 prior platinum containing 5.2 regimen.
* Patient must agree to have blood draw at pre- and post-treatment for correlative studies.
* Measurable disease by RECIST criteria v1.1.
* ECOG performance status 0 or 1.
* Patients should have no major existing co-morbidities or medical conditions that will preclude therapy in the view of the principal investigator.
* Life expectancy \> 12 weeks.
* Adequate bone marrow, hepatic and renal function as defined by the following values within 14 days prior to starting treatment:
1. Hemoglobin \>9 g/dL Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
2. Platelet count ≥ 100 x 109/L with no platelet transfusion in the past 28 days.
3. Creatinine clearance ≥50 mL/min (estimated using Cockcroft-Gault equation).
4. Total bilirubin ≤1.5 x institutional upper limit (ULN) (where bilirubin rise \> 1.5 x ULN due to Gilbert's syndrome a conjugated bilirubin ≤1.5 x ULN is required).
5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5 x ULN if no demonstrable liver metastases or ≤5 times ULN if patient has documented liver metastases.
* Women of child-bearing potential who are confirmed NOT to be pregnant. This should be evidenced by a negative urine or serum pregnancy test within 72 hours prior to start of trial treatment. Patients will be considered to be not of child-bearing potential if they are:
1. Post-menopausal - defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments, OR women under 50 years old who have been amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments and have serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and plasma oestradiol levels in the post-menopausal range for the institution.
2. Able to provide documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
3. Radiation or chemotherapy-induced oophorectomy or menopause with \> 1 year since last menses.
* Patient is willing and able to comply with the protocol for the duration of the study. including undergoing treatment and scheduled visits and examinations.
* Able to swallow, absorb, retain oral medication.
* Able to provide written, informed consent.
* Patients must have recovered from any effects of any major surgery and not have an open wound, active ulcer, or fistula.
Exclusion Criteria:
* Patients with localized advanced disease without other measurable lesion and could be treated with curative intent.
* Other malignancy within the last 5 years that would be expected to impact on overall survival. Prior malignancy with no expected impact on overall survival are allowed.
* Patients with myelodysplastic syndrome/acute myeloid leukemia history or with features suggestive of MDS/AML.
* Patients receiving radiotherapy within 2 weeks prior to study treatment.
* Major surgery within 4 weeks of starting study treatment.
* Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
* Any previous treatment with PARP inhibitor, including niraparib.
* Clinically significant (e.g. active) cardiovascular disease, uncontrolled high blood pressure. Uncontrolled high blood pressure defined as values ≥160/100 or symptomatic, refer to CTCAE.
* Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub- Arachnoids Hemorrhage (SAH) within 6 months prior to study treatment.
* Patients with increased risk of bleeding or history or evidence of hemorrhagic disorders within 6 months prior to study treatment.
* Resting ECG with QTc \> 470 msec on 2 or more time points within a 24-hour period or family history of long QT syndrome
* Persistent toxicities (Common Terminology Criteria for Adverse Event (CTCAE) \> grade 2) caused by previous cancer therapy, excluding alopecia.
* Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
* Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
* Pregnant or lactating woman.
* Participation in another clinical study with an investigational product during the chemotherapy course within 30 days prior to study treatment.
* Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
* Patients with a known hypersensitivity to investigational drugs or excipients.
* Clinical/radiological evidence of bowel obstruction (e.g. hospitalization) or symptoms of sub-acute bowel obstruction within 6 weeks prior to trial entry.
