A Study of Anti-PD-1 (Pembrolizumab) + Hormonal Therapy in HR-positive Localized IBC Patients With Non-pCR to Neoadjuvant Chemotherapy

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive pembrolizumab by
vein over about 30 minutes on Day 1 (+/- 3 days) of each 21-day cycle.

You will also receive hormonal therapy that your doctor has chosen for your standard
treatment. The study doctor will tell you which hormonal therapy you receive, its risks, and
how often you will receive it.

Length of Study:

You may continue taking the study drug for up to 24 months, as long as the doctor thinks it
is in your best interest. You will no longer be able to take the study drug if the disease
gets worse, if intolerable side effects occur, or if you are unable to follow study
directions.

Your participation on the study will be over after the follow-up visits (described below).

Study Visits:

On Day 1 of each cycle:

°Blood (about 2-3 tablespoons) will be drawn for routine tests.

On Day 1 of every other cycle:

°You will have a physical exam

At Cycle 4 and then every 3 cycles after that (before Cycle 4, 7, 10, 13 and so on), blood
(about 7 tablespoons) will be drawn for biomarker and immune system testing. This blood will
also be drawn if the disease appears to get worse.

You will have chest wall or breast photos if the doctor thinks you need them. Also you will
have imaging scans, including an EKG and either an ECHO or MUGA scan, to check the status of
the disease if the doctor thinks you need them as part of your standard care.

End-of-Treatment Visit:

As soon as possible after you stop receiving the study drugs:

- You will have a physical exam.

- Blood (about 10 tablespoons) will be drawn for routine, biomarker, and immune system
testing.

- You will have the same imaging scans you had at screening to check the status of the
disease.

- If the doctor thinks it is needed, you will have an EKG and either an ECHO or MUGA scan.

Follow-Up:

About 1 month after the last dose of study drugs, you will be asked about your health and any
side effects you may have had. You may be asked during a routine clinic visit or you may be
called. If you are called, each call should last about 2 minutes.

If you stopped taking the study drugs for reasons other than the disease getting worse, you
will be called about 24 months after your first dose of pembrolizumab to learn how you are
doing. If you are called, this should last about 3 minutes.

Inclusion Criteria:

1. Is willing and able to provide written informed consent for the trial.

2. Is a female or male and >/= 18 years of age

3. Has histological confirmation of breast carcinoma.

4. Has confirmed inflammatory breast cancer by using international consensus criteria:
(1) Onset: Rapid onset of breast erythema, edema and/or peau d'orange, and/or warm
breast, with/without an underlying breast mass. (2) Duration: History of such findings
no more than 6 months (3) Extent: Erythema occupying at least 1/3 of whole breast. (4)
Pathology: Pathologic confirmation of invasive carcinoma

5. Did not achieve pathological complete response (pCR) to any chemotherapy that was
given with the intention to induce best response prior surgery. pCR is defined as the
current American Joint Committee on Cancer (AJCC) breast cancer staging

6. Is HER2 normal, defined as HER2 0 or 1+ by IHC and negative by FISH if performed; or
HER2 is 2+ by IHC and negative by FISH; or HER2 negative by FISH if IHC is not
performed.

7. Has positive ER or PR status. ER or PR >/= 10%

8. Has a performance status of 0-1 on the ECOG Performance Scale.

9. Has adequate organ function as determined by the following laboratory values: ANC >/=
1,500 /mcL, Platelets >/=100,000 /mcL, Hgb >/= 9 g/dL, creatinine levels < 1.5 x ULN,
Total bilirubin
10. Subjects of reproductive potential must agree to avoid becoming pregnant or
impregnating a partner, respectively, while receiving study drug and for 120 days
after the last dose of study drug by complying with one of the following: (1) practice
abstinence† from heterosexual activity; OR (2) use (or have their partner use)
acceptable contraception during heterosexual activity.

11. Has negative serum or urine pregnancy test for subjects of childbearing potential
within 10 days before first dose.

12. If patient has already started hormonal blockade therapy after radiation as adjuvant
therapy, patient is eligible as long as the hormonal therapy was initiated no more
than 6 months by the time of screening and can start the study drug within 4 weeks
since the completion of screening

Exclusion Criteria:

1. Is currently participating in a study of an investigational anti-cancer agent.

2. Has a diagnosis of immunodeficiency or any other form of immunosuppressive therapy.

3. Has not recovered from adverse events due to prior therapies, i.e. monoclonal
antibody, chemotherapy, targeted small molecule therapy, radiation therapy, or
surgery. - Note: Subjects with ≤ Grade 2 neuropathy, alopecia and general disorders
and administration site conditions (per CTCAE version 4.0) are an exception to this
criterion and may qualify for the study.

4. Has a known history of prior malignancy with the exception of basal cell carcinoma of
the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ
cervical cancer, and has undergone potentially curative therapy and has no evidence of
recurrence over the last 1 year since completion of curative therapy

5. 5. Has an active autoimmune disease requiring systemic treatment within the past 3
months or a documented history of clinically severe autoimmune disease, or
immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy
would be an exception to this rule. Subjects that require intermittent use of
bronchodilators, inhaled steroid or local steroid injections to the skin would not be
excluded from the study. Subjects with hypothyroidism stable on hormone replacement or
Sjögren's syndrome will not be excluded from the study.

6. Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.

7. Has an active infection requiring systemic therapy.

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

9. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
or checkpoint pathways).

10. Has a known history of Human Immunodeficiency Virus (HIV).

11. Has a known active Hepatitis B or Hepatitis C

12. Have received a live vaccine within 30 days prior to the first dose of trial
treatment.

13. Gastrointestinal tract disease or defect or previous history of colitis

14. Distant metastasis that involves occurrence of breast cancer outside of locoregional
breast and lymph nodes area

15. Subjects requiring daily corticosteroids either via po or infusion

16. Myocardial infarction within 6 months before starting therapy, symptomatic congestive
heart failure (New York Heart Association > class II), unstable angina, or unstable
cardiac arrhythmia requiring medication.