2023-506921-12-00招募中3 期
A Randomized, Double-Blind, Phase III 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 (ER+/HER2–) Breast Cancer (KEYNOTE-756)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 424
- 试验地点
- 64
- 主要终点
- Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0
研究概览
简要总结
- To compare the rate of pCR at the time of 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.
- To compare the EFS following administration of pembrolizumab and placebo, both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies, as determined by the investigator.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •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-cN
- •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.
排除标准
- •Has a history of non-infectious pneumonitis that required treatment with steroids or has current pneumonitis.
- •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 breast cancer with lobular histology.
- •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.
- •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.
结局指标
主要结局
Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0
Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0
Event-Free Survival (EFS)
Event-Free Survival (EFS)
次要结局
- Overall Survival (OS)
- pCR Rate Using the Definition of ypT0ypN0
- pCR Rate Using the Definition of ypT0/Tis
- pCR Rate Using the Definitions of ypT0/Tis ypN0, ypT0/Tis, and ypT0 ypN0 in Participants With a Combined Positive Score [CPS] ≥1
- EFS in Participants with a CPS ≥1
- OS in Participants with a CPS ≥1
- Number of Participants Experiencing an Adverse Event (AE)
- Number of Participants Experiencing a Serious Adverse Event (SAE)
- Number of Participants Experiencing an Immune-related AE (irAE)
- Number of Study Treatment Discontinuations Due to AEs
- Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire Core 30 (QLQ-C30) Score
- Change from Baseline in EORTC Breast Cancer-Specific QoL Questionnaire (QLQ-BR23) Score
研究者
Kim Hirshfield
Scientific
Merck Sharp & Dohme LLC
研究点 (64)
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