This is an open-label, single-arm, single institution pre-operative "window of opportunity
study" of pembrolizumab in subjects with newly diagnosed triple-negative, < 3 cm, node
negative breast cancer. Subjects may not have received any prior neo/adjuvant chemotherapy,
definitive surgery or radiation treatment prior to enrollment.
The goal of this project is to determine if immune modulation through treatment with MK-3475
(Pembrolizumab) in triple negative breast cancer (TNBC) patients will alter expression of
immune tolerant markers [including PD-L1], within the primary tumor. Investigators hope to
determine if MK-3475 exposure will change the molecular signature of breast stroma from
"normal" adjacent breast tissue (non-tumor tissue) obtained prospectively at the time of
breast conserving surgery (BCS) in TNBC patients. Finally, investigators will investigate how
pembrolizumab alters breast stromal response to high dose radiation delivered by
intraoperative radiation therapy (IORT).
1. Be willing and able to provide written informed consent/assent for the trial.
2. Be > or = 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%)
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, or
breast 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 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.
11. 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
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 treatment in
the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, DCIS of the breast, or in situ cervical cancer that has
undergone potentially curative therapy.
5. Patients for whom radiotherapy for breast cancer is contraindicated because of medical
reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation).
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 of
immunosuppressive 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 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.
10. Has a history of (non-infectious) pneumonitis that required steroids or current
11. Has an active infection requiring systemic therapy.
12. 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.
13. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
14. 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
15. 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 (eg, CTLA-4,
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