I. To determine the disease free survival (DFS) at 2 years of patients with maintenance
therapy using pembrolizumab in combination with standard adjuvant hormonal therapy.
II. To determine the safety and toxicity profile of primary inflammatory breast cancer (IBC)
patients who received combination of pembrolizumab and hormone receptor blockade.
I. To investigate the association between immune related biomarkers in the peripheral blood
and tumor tissue, such as PD-L1 expression, with safety and efficacy for IBC patients treated
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat
every 21 days for up to 24 months in the absence of disease progression or unacceptable
After completion of study treatment, patients are followed up at 1 and 24 months.
- Is willing and able to provide written informed consent for the trial.
- Has histological confirmation of breast carcinoma.
- Has confirmed inflammatory breast cancer by using international consensus criteria:
- Onset: Rapid onset of breast erythema, edema and/or peau d'orange, and/or warm
breast, with/without an underlying breast mass.
- Duration: History of such findings no more than 6 months.
- Extent: Erythema occupying at least 1/3 of whole breast.
- Pathology: Pathologic confirmation of invasive carcinoma.
- 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.
- Is HER2 normal, defined as HER2 0 or 1+ by immunohistochemistry (IHC) and negative by
fluorescence in situ hybridization (FISH) if performed; or HER2 is 2+ by IHC and
negative by FISH; or HER2 negative by FISH if IHC is not performed.
- Has positive estrogen receptor (ER) or progesterone receptor (PR) status. ER or PR >=
- Has a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG)
- Absolute neutrophil count (ANC) >= 1,500/mcL.
- Platelets >= 100,000 /mcL.
- Hemoglobin (Hgb) >= 9 g/dL.
- Creatinine levels < 1.5 x upper limit of normal (ULN).
- Total bilirubin =< 1.5 x ULN.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN.
- 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. Acceptable methods of
contraception are: Single method (one of the following is acceptable): (1)
intrauterine device (IUD); (2) vasectomy of a female subject's male partner; (3)
contraceptive rod implanted into the skin. Combination method (requires use of two of
the following): (1) diaphragm with spermicide (cannot be used in conjunction with
cervical cap/spermicide); (2) cervical cap with spermicide (nulliparous women only);
(3) contraceptive sponge (nulliparous women only); (4) male condom or female condom
(cannot be used together); (5) hormonal contraceptive: oral contraceptive pill
(estrogen/progestin pill or progestin-only pill), contraceptive skin patch, vaginal
contraceptive ring, or subcutaneous contraceptive injection
- Female subjects will be considered of non-reproductive potential if they are either:
- Postmenopausal (defined as at least 12 months with no menses without an
alternative medical cause; in women < 45 years of age a high follicle stimulating
hormone (FSH) level in the postmenopausal range may be used to confirm a
post-menopausal state in women not using hormonal contraception or hormonal
replacement therapy. In the absence of 12 months of amenorrhea, a single FSH
measurement is insufficient.); OR
- Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or
bilateral tubal ligation/occlusion, at least 6 weeks prior to screening; OR
- Has a congenital or acquired condition that prevents childbearing.
- Male subjects will be considered to be of non-reproductive potential if they have
azoospermia (whether due to having had a vasectomy or due to an underlying medical
- Has negative serum or urine pregnancy test for subjects of childbearing potential
within 10 days before first dose.
- Have completed radiation (if candidate for post-mastectomy radiation) or plans to
begin radiation and endocrine therapy within 28 days.
- If patient has already started hormonal blockade therapy after radiation as adjuvant
therapy, the 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.
- Is currently participating in a study of an investigational anti-cancer agent.
- Has a diagnosis of immunodeficiency or any other form of immunosuppressive therapy.
- Has not recovered from adverse events due to prior therapies, i.e. monoclonal
antibody, chemotherapy, targeted small molecule therapy, radiation therapy, or
- Note: Subjects with grade 2 neuropathy, alopecia and general disorders and
administration site conditions (per Common Terminology Criteria for Adverse
Events [CTCAE] version 4.0) are an exception to this criterion and may qualify
for the study.
- 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.
- 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 Sjogren's
syndrome will not be excluded from the study.
- Has a history of (non-infectious) pneumonitis that required steroids or current
- Has an active infection requiring systemic therapy.
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
- 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).
- Has a known history of human immunodeficiency virus (HIV).
- Has a known active hepatitis B or hepatitis C.
- Have received a live vaccine within 30 days prior to the first dose of trial
- Gastrointestinal tract disease or defect or previous history of colitis.
- Has proven or suspected distant metastasis that involves occurrence of breast cancer
outside of locoregional breast and lymph nodes area.
- Subjects requiring daily corticosteroids either via oral route of administration (po)
- 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.