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Merck KEYNOTE-756: A randomized, double-blind, phase 3 study of pembrolizumab versus placebo in combination with neoadjuvant chemotherapy and adjuvant endocrine therapy for the treatment of high-risk, early-stage estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer

Description

The primary objective is to:

  • Compare the rate of pathological complete response (pCR) at the time of definitive surgery, using the definition of ypT0/Tis ypN0 as assessed by the local pathologist, of pembrolizumab versus placebo, both in combination with the protocol-specified neoadjuvant anticancer therapies
  • Compare event-free survival (EFS) following administration of pembrolizumab and placebo, both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies, as determined by the investigator

Status

Accepting new patients

Primary Study Objective(s)

The purpose of this study is to assess the efficacy and safety of pembrolizumab vsersus 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.

Core eligibility

Note: This is only a partial list of eligibility criteria.

Including patients who:

  • Have 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 (Inflammatory breast cancer is allowed.)
  • Have centrally confirmed ER+/HER2-, grade III breast cancer of ductal histology, according to the most recent American Society of Clinical Oncology/College of American Pathologist guiveelines
  • Provide 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, and PD-L1 status
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 10 days prior to initiation of study treatment
  • Are male and agree to use contraception during the treatment period and for at least 12 months (for participants who received cyclophosphamide) or six months (for participants who did not receive cyclophosphamide) after the last dose of study treatment and refrains from donating sperm during this period
  • Are female and agree to use effective contraception during the treatment period and for at least 12 months (for participants who received cyclophosphamide) or six months (for participants who did not receive cyclophosphamide) after the last dose of study treatment with pembrolizumab or placebo
  • Have adequate organ function

Excluding patients who:

  • Have a history of non-infectious pneumonitis that required treatment with steroids or has current pneumonitis.
  • Have breast cancer with lobular histology
  • Have bilateral invasive breast cancer
  • Have metastatic (stage IV) breast cancer
  • Have multi-centric breast cancer (presence of more than 1 tumor in different quadrants of the breast)
  • Have 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
  • Have ER-, progesterone receptor positive breast cancer
  • Have undergone excisional biopsy of the primary tumor and/or axillary lymph nodes or has undergone sentinel lymph node biopsy prior to study treatment
  • Have a known additional, invasive, malignancy that is progressing or required active treatment in the last five years
  • Have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within seven days prior to the first dose of study treatment
  • Have an active autoimmune disease that has required systemic treatment (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) in the past two years (Replacement therapy [e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency] is not considered a form of systemic treatment.)
  • Have a known history of active tuberculosis (Bacillus tuberculosis)
  • Have an active infection requiring systemic therapy
  • Have left ventricular ejection fraction (LVEF) of less than 50 percent or less than the institution limit of normal, as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed at screening
  • Have other significant cardiac disease, such as:  History of myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass within the last 6 months; or congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA Class III or IV
  • Have a known history of human immunodeficiency virus (HIV) infection
  • Have a known history of hepatitis B or known active hepatitis C virus infection
  • Have received prior treatment for breast cancer
  • Have 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)
  • Have received a live vaccine within 30 days prior to the first dose of study treatment.
  • Have severe hypersensitivity (≥Grade III) to any of the components or excipients used in the study treatments
  • Are or was enrolled in a study of an investigational agent and received study therapy, or used an investigational device within four weeks (12 months for an investigational agent or device with anticancer or antiproliferative properties) prior to the first dose of study treatment
  • Are 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

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

Learn more about breast cancer

     

Accepting new patients

 

Learn more at

clinicaltrials.gov

 

Principal Investigator(s)

Damien Hansra

Cynthia Lynch

Sramila Aithal

Eugene Ahn

Asha Karippot