Trial Search Results

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)

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.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Merck Sharp & Dohme Corp.

Stanford Investigator(s):

Intervention(s):

  • Biological: Pembrolizumab (K)
  • Drug: Placebo (P)
  • Drug: Paclitaxel (X)
  • Drug: Doxorubicin (A)
  • Drug: Epirubicin (E)
  • Drug: Cyclophosphamide (C)
  • Drug: Endocrine therapy
  • Radiation: Radiation therapy
  • Procedure: Surgery

Phase:

Phase 3

Eligibility


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.

   - 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.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Kaitlin Zablotsky
650-725-2142
Recruiting