| Eligibility |
Inclusion Criteria:
- Histologically confirmed advanced breast cancer not amenable to curative treatment by
surgery or radiotherapy, that is amenable to biopsy
- Radiographically measurable disease by RECIST v1.1
- Age = 18 years
- Life expectancy of more than 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
- Signed informed consent form
- Patients with a standard 12-lead electrocardiogram (ECG) with the following parameters
at screening (defined as the mean of the triplicate ECGs):
1. QTc interval at screening < 481 msec
2. Resting heart rate 50-100bpm
- Adequate hepatic, bone marrow, and renal function at the time of enrollment:
1. Bone Marrow: Absolute neutrophil count (ANC) = 1,500/mm3; Platelets =
100,000/mm3; Hemoglobin = 9.0 g/dL. Patients must be able to meet the criteria
without transfusion or receipt of colony stimulating factors within 2 weeks
before obtaining sample
2. Creatinine clearance = 60 mL/min based on Cockcroft-Gault equation
3. Hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) = 2.5 × the upper normal limit of institution's normal range. Total
bilirubin = 1.5 × the upper normal limit of institution's normal range, except
for subjects with documented history of Gilbert's syndrome who may enroll at
Investigator discretion. For subjects with liver metastases, AST and ALT < 5 ×
the upper normal limit of institution's normal range, and total bilirubin >1.5 -
3.0 x the upper normal limit of institution's normal range are acceptable as long
as there is no persistent nausea, vomiting, right upper quadrant pain or
tenderness, fever, rash, or eosinophilia
4. Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) must be = 2 X the
upper limit of the institution's normal range and International Normalized Ratio
(INR) < 2. Subjects on anticoagulation (such as coumadin) will be permitted to
enroll as long as the INR is in the acceptable therapeutic range as determined by
the investigator
- Patients may have received an unlimited number of prior therapies. The last dose of
systemic therapy must have occurred a minimum of 2 weeks prior to C1D1.
- Patients must have fully recovered from all effects of surgery. Patients must have had
at least two weeks after minor surgery and four weeks after major surgery before
starting therapy. Minor procedures requiring conscious sedation such as endoscopies or
mediport placement may only require a 24-hour waiting period, but this must be
discussed with an investigator
- Women of childbearing potential must have a negative serum pregnancy test within 14
days prior to initiation of treatment and/or postmenopausal women must be amenorrheic
for at least 12 months to be considered of non-childbearing potential
- Patient is capable of swallowing pills whole
- Subject, or legally authorized representative (LAR) is capable of understanding and
complying with parameters as outlined in the protocol and able to sign and date the
informed consent, approved by the IRB, prior to the initiation of any screening or
study-specific procedures
- Patient, or LAR, must consent to multiple biopsies during study.
Exclusion Criteria:
- Prior disease progression while receiving anti-PD-1 or anti-PD-L1 therapy within 6
months of use
- Prior exposure to PARP inhibitor-based therapy
- Patients with known untreated central nervous system (CNS) metastases
- Recent severe infection or antibiotic use, or known chronic infection with human
immunodeficiency virus (HIV) or hepatitis B virus
- Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
- Diagnosis of immunodeficiency or is receiving systemic steroid or other
immunosuppressive therapy
- Active autoimmune disease that has required systemic treatment in the past 2 years
- History of tuberculosis
- History of allogenic bone marrow transplant or solid organ transplant
- History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan
- Life-threatening visceral disease or other severe concurrent disease that would, in
the investigator's judgment, cause unacceptable safety risks, contraindicate patient
participation in the clinical study or compromise compliance with the protocol
- Live vaccine administration within 30 days of planned start of study therapy
- Cardiovascular disease problems including unstable angina, therapy for lifethreatening
ventricular arrhythmia, or myocardial infarction, stroke within the last 6 months, or
a diagnosis of congestive heart failure
- Patient has impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of the study drugs
- Presence of a psychiatric illness or social situation that would limit compliance with
study requirements
- Women who are pregnant or breastfeeding
- Patients with history of another active malignancy within the past 2 years, excluding
non-melanoma carcinoma of the skin
- Patients receiving any other investigational agents
- Patients must not have had radiotherapy encompassing >20% of the bone marrow
- Patients must not have current evidence of any condition, therapy, or laboratory
abnormality (including active or uncontrolled myelosuppression [ie, anemia,
leukopenia, neutropenia, thrombocytopenia]) that might confound the results of the
study or interfere with the patient's participation for the full duration of the study
treatment or that makes it not in the best interest of the patient to participate
- Patients must not be considered a poor medical risk due to a serious, uncontrolled
medical disorder, nonmalignant systemic disease, or active, uncontrolled infection.
- Current use of potent P-gp inhibitors within 7 days prior to randomization.
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