Study of Pembrolizumab (MK-3475) Versus Placebo in Combination With Neoadjuvant Chemotherapy & Adjuvant Endocrine Therapy in the Treatment of Early-Stage Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (MK-3475-756/KEYNOTE-756)

Running, not enrolling · Phase 3 · Has a placebo group

Conditions studied: Breast Cancer

In brief

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) versus placebo in combination with neoadjuvant (pre-surgery) chemotherapy and adjuvant (post-surgery) endocrine therapy in the treatment of adults who have high-risk early-stage estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer. The primary study hypotheses are: 1) pembrolizumab is superior to placebo, both in combination with the protocol-specified neoadjuvant anticancer therapy, as assessed by pathological Complete Response (pCR) rate defined by the local pathologist, and 2) pembrolizumab is superior to placebo (both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies) as assessed by Event-Free Survival (EFS) as determined by the investigator. The study is considered to have met its primary objective if pembrolizumab is superior to placebo with respect to either pCR (ypT0/Tis ypN0) or EFS.

Key facts

Study ID

NCT03725059

Run by

Merck Sharp & Dohme LLC

People needed

1240

Starts

2018-12-27

Expected to finish

2031-01-24

Last updated by the study team

2025-07-11

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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.

Where it is running

• Cancer Treatment Centers of America at Western Regional Medical Center ( Site 0001) — Goodyear, Arizona, United States
• Arizona Oncology Associates PC- HOPE ( Site 8008) — Tucson, Arizona, United States
• Cedars Sinai Medical Center Samuel Oschin Comp. Cancer Institute ( Site 0079) — Los Angeles, California, United States
• El Camino Hospital Cancer Center ( Site 0004) — Mountain View, California, United States
• Stanford Cancer Center ( Site 0072) — Palo Alto, California, United States
• UC Davis Comprehensive Cancer Center ( Site 0073) — Sacramento, California, United States
• University of Colorado, Anschutz Cancer Pavilion ( Site 0008) — Aurora, Colorado, United States
• Baptist MD Anderson Cancer Center ( Site 0014) — Jacksonville, Florida, United States
• Southeastern Regional Medical Center, Inc. ( Site 0075) — Newnan, Georgia, United States
• The University of Chicago Medical Center ( Site 0080) — Chicago, Illinois, United States
• Orchard Healthcare Research Inc. ( Site 0020) — Skokie, Illinois, United States
• Midwestern Regional Medical Center, Inc. ( Site 0077) — Zion, Illinois, United States
• Goshen Center for Cancer Care ( Site 0021) — Goshen, Indiana, United States
• MercyOne Waterloo Cancer Center ( Site 0016) — Waterloo, Iowa, United States
• James Graham Brown Cancer Center ( Site 0022) — Louisville, Kentucky, United States
• Maryland Oncology Hematology, P.A. ( Site 8007) — Bethesda, Maryland, United States
• Massachusetts General Hospital ( Site 0024) — Boston, Massachusetts, United States
• MGH - North Shore Cancer Center ( Site 0081) — Danvers, Massachusetts, United States
• MGH Newton-Wellesley Hospital's Vernon Cancer Center ( Site 0082) — Newton, Massachusetts, United States
• Henry Ford Health System ( Site 0028) — Detroit, Michigan, United States
• Mayo Clinic and Medical School (Rochester) ( Site 0029) — Rochester, Minnesota, United States
• St. Vincent Frontier Cancer Center ( Site 0033) — Billings, Montana, United States
• Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0039) — Omaha, Nebraska, United States
• Holy Name Medical Center ( Site 0041) — Teaneck, New Jersey, United States
• Southern Cancer Center, PC ( Site 8003) — Daphne, Alabama, United States

Full record on ClinicalTrials.gov

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