Effects of MK-3475 (Pembrolizumab) on the Breast Tumor Microenvironment in Triple Negative Breast Cancer

Inclusion Criteria:

1. Be willing and able to provide written informed consent/assent for the trial.

2. Be ≥ 21 years of age on day of signing informed consent.

3. Histologically proven invasive breast carcinoma with triple negative receptor status (Estrogen receptor, Progesterone receptor and HER2 negative by IHC and FISH).Patients who are weekly positive for the estrogen or progesterone receptor (i.e., <or = 10%) are eligible.

4. Clinically ≤ 3 cm unifocal lesion by imaging or physical examination.

5. Clinically node negative, no evidence of metastatic disease.

6. No prior anti-cancer therapy including investigational agents, radiation therapy, orbreast resection within 6 months of study entry.

7. Breast size B cup or larger, to allow for IORT procedure.

8. Have a performance status of 0 or 1 on the ECOG Performance Scale.

9. Demonstrate adequate organ function.

10. Female subject of childbearing potential should have a negative urine or serumpregnancy within 72 hours prior to receiving the first dose of study medication. Ifthe urine test is positive or cannot be confirmed as negative, a serum pregnancytest will be required.

11. Female subjects of childbearing potential must be willing to use an adequate methodof contraception for the course of the study through 120 days after the last dose ofstudy medication.

Exclusion Criteria:

1. Multifocal disease within the breast.

2. Has primary lesion > 3 cm in size radiographically or by physical examination.Pathologically proven nodal disease at diagnosis is not allowed.

3. Has metastatic disease.

4. Has a known additional malignancy that is progressing or requires active treatmentin the last 5 years. Exceptions include basal cell carcinoma of the skin, squamouscell carcinoma of the skin, DCIS of the breast, or in situ cervical cancer that hasundergone potentially curative therapy.

5. Patients for whom radiotherapy for breast cancer is contraindicated because ofmedical reasons (e.g., connective tissue disorder or prior ipsilateral breastradiation).

6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) or any other form ofimmunosuppressive therapy within 7 days prior to the first dose of trial treatment.

7. Has a known history of active TB (Bacillus Tuberculosis).

8. Has severe hypersensitivity (≥ Grade 3) to pembrolizumab or any of its excipients.

9. Has active autoimmune disease that has required systemic treatment in the past 2years (i.e., with use of disease modifying agents, corticosteroids orimmunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, orphysiologic corticosteroid replacement therapy for adrenal or pituitaryinsufficiency, etc.) is not considered a form of systemic treatment.

10. Has a history of (non-infectious) pneumonitis that required steroids or currentpneumonitis.

11. Has an active infection requiring systemic therapy.

12. Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the study, interfere with thesubject's participation for the full duration of the study, or is not in the bestinterest of the subject to participate, in the opinion of the treating investigator.

13. Has known psychiatric or substance abuse disorders that would interfere withcooperation with the requirements of the trial.

14. Is pregnant or breastfeeding, or expected to conceive children within the projectedduration of the study, starting with the screening visit through 120 days after thelast dose of trial treatment. The effects of MK-3745 on the developing human fetus are unknown. For this reasonand because monoclonal antibody neoplastic agents are known to be teratogenic, womenof child-bearing potential must agree to use adequate contraception (hormonal orbarrier method of birth control; abstinence) prior to study entry and for theduration of study participation. Should a woman become pregnant or suspect she ispregnant while she is participating in this study, she should inform her treatingphysician immediately.

15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent orwith an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg,CTLA-4, OX-40, CD137).

16. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

17. Has received a live vaccine within 30 days of planned start of study therapy.

18. Has a medical history of allogenic stem cell transplant

19. Has received a solid organ transplant

20. Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIVtesting is required unless mandated by local health authority.