Pembrolizumab with and without Intra-operative Radiation Therapy in Treating Patients with Triple Negative Breast Cancer

Inclusion Criteria

• Ability to understand and the willingness to sign a written informed consent document.
• Be >= 21 years of age on day of signing informed consent
• Histologically proven invasive breast carcinoma with triple negative receptor status (estrogen receptor, progesterone receptor and HER2 negative by immunohistochemistry [IHC] and/or fluorescence in situ hybridization [FISH]); patients who are weekly positive for the estrogen or progesterone receptor (i.e. =< 10%) are eligible
• Clinically =< 3 cm unifocal lesion by imaging or physical examination
• Clinically node negative, no evidence of metastatic disease
• No prior systemic anti-cancer therapy including investigational agents, radiation therapy, or breast resection within 6 months of study entry
• Breast size B cup or larger, to allow for IORT procedure
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) >= 1,500 /uL
• Platelets >= 100,000 /uL
• Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L; criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
• Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30 mL/min for participant with creatinine levels > 1.5 x institutional ULN.
• Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN.
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN.
• International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants.
• Activated partial thromboplastin Time (aPTT) =< 1.5 X ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Note: In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication
• Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication * Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject

Exclusion Criteria

• Multifocal disease within the breast
• Has primary lesion > 3 cm in size radiographically or by physical examination; pathologically proven nodal disease at diagnosis is not allowed
• Has metastatic disease
• Has a known additional malignancy that is progressing or requires active treatment in the last 5 years; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ ductal carcinoma or cervical cancer that have undergone potentially curative therapy.
• Patients for whom radiotherapy for breast cancer is contraindicated because of medical reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation)
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dose exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known history of active TB (Bacillus tuberculosis)
• Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expected to conceive children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment; the effects of MK-3745 on the developing human fetus are unknown; for this reason and because monoclonal antibody neoplastic agents are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137).
• Has known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) infection. * Note: No testing for hepatitis B and hepatitis C is required unless mandated by local health authority
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study therapy. Administration of killed vaccines is allowed
• Has a medical history of allogenic stem cell transplant
• Has received a solid organ transplant
• Has a known history of human immunodeficiency virus (HIV) infection * Note: No HIV testing is required unless mandated by local health authority