Study participants will receive 8 cycles of neoadjuvant study treatment and then will undergo
surgery for their breast cancer. After surgery, participants will receive 9 cycles of study
treatment and up to 10 years of variable endocrine therapy. Each cycle is 21 days long.
Inclusion Criteria:
- Has a localized invasive breast ductal adenocarcinoma, confirmed by the local
pathologist, that includes either T1c-T2 (tumor size ≥2 cm), clinical node stage
(cN)1-cN2, or T3-T4, cN0-cN2. Note: Inflammatory breast cancer is allowed.
- Has centrally confirmed ER+/HER2-, Grade 3 breast cancer of ductal histology,
according to the most recent American Society of Clinical Oncology/College of American
Pathologist guidelines.
- Provides a new or recently obtained core needle biopsy, consisting of multiple cores,
taken from the primary breast tumor(s) for central determination of HR status (ER and
progesterone receptor), HER2, grade, and PD-L1 status.
Note: Sponsor agreement is required for formalin-fixed paraffin-embedded (FFPE) tumor
tissue sample or slides that were obtained greater than 60 days prior to the date that the
documented informed consent was obtained.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as
assessed within 10 days prior to initiation of study treatment.
- Male participants must agree to use contraception during the treatment period and for
at least 12 months (for participants who received cyclophosphamide) or 6 months (for
participants who did not receive cyclophosphamide) after the last dose of study
treatment and refrain from donating sperm during this period.
- Female participants must agree to use effective contraception during the treatment
period and for at least 12 months (for participants who received cyclophosphamide) or
6 months (for participants who did not receive cyclophosphamide) after the last dose
of study treatment with pembrolizumab or placebo.
- Has adequate organ function.
Exclusion Criteria:
- Has a history of non-infectious pneumonitis that required treatment with steroids or
has current pneumonitis.
- Has breast cancer with lobular histology.
- Has bilateral invasive breast cancer.
- Has metastatic (Stage IV) breast cancer.
- Has multi-centric breast cancer (presence of more than 1 tumor in different quadrants
of the breast).
- Has any of the following clinical lymph node staging per current American Joint
Committee on Cancer (AJCC) staging criteria for breast cancer staging based on
radiological and/or clinical assessment: cN3, cN3a, cN3b, or cN3c.
- Has ER-, progesterone receptor positive breast cancer.
- Has undergone excisional biopsy of the primary tumor and/or axillary lymph nodes or
has undergone sentinel lymph node biopsy prior to study treatment.
- Has a known additional, invasive, malignancy that is progressing or required active
treatment in the last 5 years.
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the
skin, ductal breast carcinoma in situ, or cervical carcinoma in situ that has undergone
potentially curative therapy are not excluded.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- Has an 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) Note: Replacement therapy (e.g. thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency)
is not considered a form of systemic treatment.
- Has a known history of active tuberculosis (Bacillus tuberculosis).
- Has an active infection requiring systemic therapy.
- Has left ventricular ejection fraction (LVEF) of <50% or below the institution limit
of normal, as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
performed at screening.
- Has other significant cardiac disease, such as: 1) History of myocardial infarction,
acute coronary syndrome, or coronary angioplasty/stenting/bypass within the last 6
months. or 2) Congestive heart failure (CHF) New York Heart Association (NYHA) Class
II-IV or history of CHF NYHA Class III or IV.
- Has a known history of human immunodeficiency virus (HIV) infection.
- Has a known history of hepatitis B or known active hepatitis C virus infection.
- Has received prior treatment for breast cancer.
- Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1),
anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent
directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic
T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137).
- Has received a live vaccine within 30 days prior to the first dose of study treatment.
- Has severe hypersensitivity (≥Grade 3) to any of the components or excipients used in
the study treatments.
- Is/was enrolled in a study of an investigational agent and received study therapy, or
used an investigational device within 4 weeks (12 months for an investigational agent
or device with anticancer or antiproliferative properties) prior to the first dose of
study treatment.
- Is pregnant, breastfeeding, or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 12 months
(for participants who received cyclophosphamide) or 6 months (for participants who did
not receive cyclophosphamide) after the last dose of study treatment.
