Main Inclusion Criteria:
- Histologically proven advanced (unresectable) or metastatic cancer as outlined below
1. Patients with triple-negative breast cancer (TNBC) who have been treated with at
least 1 prior regimen for advanced/metastatic disease or who relapsed/progressed
while on or within 1 month from completion of adjuvant chemotherapy
Phase 1: Up to 3 lines of prior chemotherapy are allowed
Phase 2: Up to 2 lines of prior chemotherapy are allowed
2. Patients with high-grade serous ovarian, fallopian tube, or primary peritoneal
cancer who have recurrent disease and have been previously treated with
chemotherapy for advanced/metastatic disease and who experienced a response
lasting at least 6 months to first-line platinum-based therapy but currently
considered platinum-resistant
Phase 1: Up to 4 lines of prior chemotherapy are allowed
Phase 2: Up to 3 lines of prior chemotherapy are allowed
- 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
Main Exclusion Criteria:
- Progressed while on platinum treatment or within 1 month from completion of
platinum-containing regimen in any line of 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 5 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
- 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
- History of interstitial lung disease
- Known history of platelet transfusion for chemotherapy-induced thrombocytopenia or
persistent (> 4 weeks) Grade 3 hematological toxicity or fatigue from prior cancer
therapy
- Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2
- Prior treatment with a known poly(ADP-ribose) polymerase (PARP) inhibitor
- Heart-rate corrected QT interval (QTc) prolongation > 470 msec at screening
- Known history of myelodysplastic syndrome (MDS) or a pre-treatment cytogenetic
testing result at risk for a diagnosis of MDS/acute myeloid leukemia (AML)
- Receiving concomitant medications that prolong QTc and is unable to discontinue use
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
To evaluate the safety and tolerability of combination treatment with niraparib and pembrolizumab using Common Terminology Criteria for Adverse Events (CTCAE, v4.03)
Overall Response Rate (ORR)
Duration of Response (DOR)
Disease Control Rate (DCR)
Progression Free Survival (PFS)
Overall Survival (OS)
To evaluate the Area Under the Curve (AUC), Minimum concentration (Cmin)
Maximum Concentration (Cmax)
Clearance after oral administration (CL/F)
Volume of Distribution after oral administration (Vz/F)
AUC at steady state (AUCss)
Cmin at steady state (Cmin,ss)
Cmax at steady state (Cmax,ss)