Niraparib in Combination With Pembrolizumab in Patients With Triple-negative Breast Cancer or Ovarian Cancer

Exclusion Criteria

• •2. Phase 2 patients (breast or ovarian cancer)
• •* Patients with advanced or metastatic breast cancer must have TNBC. Patients with advanced or metastatic disease may have received up to 2 lines of cytotoxic therapy. Adjuvant and/or neoadjuvant therapies are not counted in the number of lines of therapy. TNBC patients who have previously received platinum chemotherapy in the metastatic setting are allowed to enroll in the study as long as they did not progress while on or within 8 weeks from the day of the last platinum administration.
• •Archival tumor tissue available or a fresh biopsy must be obtained prior to study treatment initiation
• •Measurable lesions by RECIST v1.1
• •Eastern Cooperative Oncology Group (ECOG) 0 or 1
• •Adequate organ function
• •Able to take oral medications
• •Female patient, if of childbearing potential, has a negative serum pregnancy test within 72 hours of taking study medication and agrees to abstain from activities that could result in pregnancy from enrollment through 120 days after the last dose of study treatment
• •Male patient agrees to use an adequate method of contraception
• •Patients with primary platinum refractory ovarian cancer (ie, progressive disease on or within 6 months of first-line platinum therapy)
• •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis Note: Patients previously treated for brain metastases may be able to participate provided they are stable
• •Patient has a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer
• •Poor medical risk
• •Condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results, or interfere with the patient's participation for the full duration of the study treatment.
• •Pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study
• •Immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
• •Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• •Known active hepatitis B or hepatitis C
• •Active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• •Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• •Prior treatment with a known poly(ADP-ribose) polymerase (PARP) inhibitor
• •Heart-rate corrected QT interval (QTc) prolongation \> 470 msec at screening
• •Known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)