| Eligibility |
Inclusion Criteria:
1. Be willing and able to provide written informed consent for the trial. The subject may
also provide consent for Future Biomedical Research. However, the subject may
participate in the main trial without participating in Future Biomedical Research.
2. Be a male or female subject greater than or equal to 18 years of age on day of signing
informed consent.
3. Have locally confirmed TNBC, as defined by the most recent ASCO/CAP guidelines.
4. Have previously untreated locally advanced non-metastatic (M0) TNBC defined as the
following combined primary tumor (T) and regional lymph node (N) staging per the
current AJCC Version 8 staging criteria for breast cancer staging criteria as assessed
by the investigator based on radiological and/or clinical assessment:
- T1c, N1-N2
- T2, N0-N2
- T3, N0-N2
- T4a-d, N0-N2 Note: bilateral tumors (i.e., synchronous cancers in both breasts)
and/or multi-focal (i.e., 2, separate lesions in the same quadrant)/multi-centric
(i.e., 2 separate lesions in different quadrants) tumors are allowed, as well as
inflammatory breast cancer, and the tumor with the most advanced T stage should
be used to assess the eligibility.
5. Provide a core needle biopsy consisting of at least 1 separate tumor-bearing cores
from the primary tumor at screening for translational research (archival is acceptable
if sufficient tumor is available; slides are acceptable if at least 15 are available)
6. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed
within 14 days of treatment initiation.
7. Demonstrate adequate organ function. All screening labs should be performed within 14
days of treatment initiation.
8. Have left ventricular ejection fraction (LVEF) of =50% or = institution lower limit of
normal (LLN) as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA)
scan performed at screening.
9. Males and female subjects of childbearing potential (Section 5.7.2 - Contraception)
must be willing to use an adequate method of contraception as outlined in Section
5.7.2 - Contraception, for the course of the study through 12 months after the last
dose of study medication for subjects who have received cyclophosphamide, and 6 months
after the last dose of study medication for subjects who did not.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
10. (Female subject of childbearing potential) Have a negative urine or serum pregnancy
test within 72 hours prior to receiving the first dose of study medication. If the
urine test is positive or borderline a serum pregnancy test will be required.
Exclusion Criteria:
1. Has a history of invasive malignancy =5 years prior to signing informed consent except
for adequately treated basal cell or squamous cell skin cancer or in situ cervical
cancer.
2. Has received prior chemotherapy, targeted therapy, and radiation therapy within the
past 12 months.
3. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
an agent directed to another co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40,
CD137) or has previously participated in MK-3475 clinical trials.
4. Is currently participating in or has participated in an interventional clinical trial
with an investigational compound or device within 4 weeks of the first dose of
treatment in this current trial.
Note: subject should be excluded if he/she received an investigational agent with
anti-cancer or anti-proliferative intent within the last 12 months.
5. Has received a live vaccine within 30 days of the first dose of study treatment.
Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines
and are allowed; however intranasal influenza vaccines (e.g., FluMist®) are live
attenuated vaccines, and are not allowed.
6. Has an active autoimmune disease that has required systemic treatment in 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) is not considered a form
of systemic treatment.
7. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment.
8. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
9. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
10. Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.
11. Has an active infection requiring systemic therapy.
12. Has significant cardiovascular disease, such as:
- History of myocardial infarction, acute coronary syndrome or coronary
angioplasty/stenting/bypass grafting within the last 6 months
- Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or
history of CHF NYHA class III or IV
13. Has a history or current evidence of any condition, therapy, lab abnormality or other
circumstance that might expose the subject to risk by participating in the trial,
confound the results of the trial, or interfere with the subject's participation for
the full duration of the trial in the opinion of the Investigator.
14. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial in the opinion of the Investigator.
15. Is pregnant or breastfeeding, or expecting to conceive children within the projected
duration of the trial, starting with the screening visit through 12 months after the
last dose of trial treatment for subjects who have received cyclophosphamide, and for
6 months after the last dose of study medication for subjects who have not.
16. Has a known hypersensitivity to the components of the study therapy or its analogs.
17. Has a known history of active TB (Bacillus Tuberculosis).
18. Allergy to ciprofloxacin (or other quinolones).
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