Niraparib and TSR-042 for the Treatment of BRCA-Mutated Unresectable or Metastatic Breast, Pancreas, Ovary, Fallopian Tube, or Primary Peritoneal Cancer

Participant must have breast, pancreas, ovary, fallopian tube or primary peritoneal cancer that is unresectable or metastatic, with a pathogenic mutation in BRCA1 or BRCA2 (either germline or somatic) as confirmed by next generation gene sequencing such as University of Washington (UW) OncoPlex assay or equivalent, and who have experienced progression or been intolerant to standard therapies for their disease.

* Breast cancer patients with or without HER2+, estrogen receptor (ER)+, and/or progesterone receptor (PR)+ disease, as determined by pathological report, are allowed

Participant must be able and willing to undergo pre-treatment and on-treatment biopsy

Participant must have life expectancy of 4 months or greater

Tumor must be measurable according to Response Evaluation Criteria in Solid Tumors (RECIST)1.1 criteria

Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1

Participant must be \>= 18 years of age

Patient must be able to tolerate oral medication

Absolute neutrophil count \>= 1,500/uL

Platelets \>= 100,000/uL

Hemoglobin \>= 9 g/dL

Serum creatinine =\< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance \>= 60 mL/min using the Cockcroft-Gault equation

Total bilirubin =\< 1.5 x ULN (=\< 2.0 in patients with known Gilberts syndrome) OR direct bilirubin =\< 1 x ULN

Aspartate aminotransferase and alanine aminotransferase =\< 2.5 x ULN unless liver metastases are present, in which case they must be =\< 5 x ULN

International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

Asymptomatic patients with stable brain metastases must have no evidence of bleeding and no need for steroids or anti-epileptic medications for at least 7 days prior to day 1

Participants receiving corticosteroids may continue as long as their dose is stable for at least 4 weeks prior to initiating protocol therapy

Female participant has a negative urine or serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment or is of nonchildbearing potential. Nonchildbearing potential is defined as follows (by other than medical reasons):

* \>= 45 years of age and has not had menses for \> 1 year

* Patients who have been amenorrhoeic for \< 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation

* Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient

Participant must agree to not breastfeed during the study or for 180 days after the last dose of study treatment

Male participant agrees to use an adequate method of contraception starting with the first dose of study treatment through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient

Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent

Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment

Prior treatment with a PARP inhibitor is allowed as long as patient has not had previous exposure to immune checkpoint inhibitor including inhibitors of PD1, PD-L1 or CTLA4

Prior treatment with immune checkpoint inhibitor including inhibitors of PD1, PD-L1 or CTLA4 is allowed as long as patient has not had previous exposure to PARP inhibitor

What this study is about