A Randomized, Multicenter, Double-blind, Placebo-controlled Phase 3 Study of Nivolumab Versus Placebo in Combination With Neoadjuvant Chemotherapy and Adjuvant Endocrine Therapy in Patients With High-risk, Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Primary Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 521
- 试验地点
- 232
- 主要终点
- Pathological Complete Response (pCR) Rate
研究概览
简要总结
A randomized multi-arm study evaluating the efficacy and safety of nivolumab versus placebo in combination with neoadjuvant (pre-surgery) chemotherapy and adjuvant (post-surgery) endocrine therapy in participants with high-risk, estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+, HER2-) early stage breast cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Localized invasive breast ductal carcinoma, confirmed by the local pathologist, that includes the following combined primary tumor and clinical node (cN) categories: T1c (tumor size = 2 cm)-T2 (tumor size > 2 cm), cN1-N2 OR T3-T4, cN0-cN
- •Note: Axillary lymph node status must be assessed by fine needle biopsy or core biopsy.
- •Estrogen receptor-positive (ER+) breast cancer (BC) and with or without progesterone receptor (PgR) expression (determined on the most recently analyzed tissue sample, tested locally, and confirmed by the central laboratory), as defined in the relevant American Society of Clinical Oncology (ASCO)- College of American Pathologists (CAP) Guidelines.
- •Human epidermal growth factor receptor 2 (HER2-) BC tested in the local laboratory, defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0, 1+, or 2+.
- •Tumor Grade 3 of ductal histology, Or Tumor Grade 2 of ductal histology having an ER expression level percentage between 1-10%
- •Must agree to provide primary breast tumor tissue at baseline and at surgery
- •Must be deemed eligible for surgery
- •Males and females must agree to follow specific methods of contraception, if applicable, while participating in the trial
- •Must have an Eastern Cooperative Oncology Group (ECOG) scale performance status of 0 or 1
排除标准
- •Breastfeeding, pregnant, or expecting to conceive or father children within the projected duration of the study, starting with the screening through 12 months for participants who receive cyclophosphamide, or 6 months for participants who do not receive cyclophosphamide, after the last dose of study treatment
- •Prior treatment with chemotherapy, endocrine therapy (ET), targeted therapy, and/or radiation therapy for the currently diagnosed breast cancer prior to enrollment
- •Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- •Significant cardiovascular disease such as left ventricular ejection fraction (LVEF) < 50% at baseline as assessed by echocardiography (ECHO) or multigated acquisition (MUGA) scan performed at screening, or Class III or IV myocardial disease as described by the New York Heart Association
- •History of ipsilateral invasive BC, regardless of treatment, ipsilateral ductal carcinoma in situ treated with radiation, or contralateral invasive BC, at any time
- •Definitive clinical or radiologic evidence of metastatic disease
- •Multicentric BC (the presence of > 1 tumor in different quadrants of the breast)
- •Bilateral invasive BC
- •Other protocol-defined inclusion/exclusion criteria apply
研究组 & 干预措施
Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET
Nivolumab with paclitaxel followed by nivolumab with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then nivolumab with adjuvant (post-surgery) endocrine therapy of investigator's choice
干预措施: nivolumab (Biological)
Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET
Nivolumab with paclitaxel followed by nivolumab with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then nivolumab with adjuvant (post-surgery) endocrine therapy of investigator's choice
干预措施: paclitaxel (PTX) (Drug)
Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET
Nivolumab with paclitaxel followed by nivolumab with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then nivolumab with adjuvant (post-surgery) endocrine therapy of investigator's choice
干预措施: anthracycline (Drug)
Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET
Nivolumab with paclitaxel followed by nivolumab with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then nivolumab with adjuvant (post-surgery) endocrine therapy of investigator's choice
干预措施: cyclophosphamide (Drug)
Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET
Nivolumab with paclitaxel followed by nivolumab with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then nivolumab with adjuvant (post-surgery) endocrine therapy of investigator's choice
干预措施: Endocrine Therapy (Drug)
Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET
Nivolumab with paclitaxel followed by nivolumab with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then nivolumab with adjuvant (post-surgery) endocrine therapy of investigator's choice
干预措施: Surgery (Procedure)
Arm B: Placebo combined with neoadjuvant CT and then adjuvant ET
Nivolumab placebo with paclitaxel followed by nivolumab placebo with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then adjuvant (post-surgery) endocrine therapy of investigator's choice
干预措施: paclitaxel (PTX) (Drug)
Arm B: Placebo combined with neoadjuvant CT and then adjuvant ET
Nivolumab placebo with paclitaxel followed by nivolumab placebo with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then adjuvant (post-surgery) endocrine therapy of investigator's choice
干预措施: nivolumab placebo (Other)
Arm B: Placebo combined with neoadjuvant CT and then adjuvant ET
Nivolumab placebo with paclitaxel followed by nivolumab placebo with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then adjuvant (post-surgery) endocrine therapy of investigator's choice
干预措施: anthracycline (Drug)
Arm B: Placebo combined with neoadjuvant CT and then adjuvant ET
Nivolumab placebo with paclitaxel followed by nivolumab placebo with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then adjuvant (post-surgery) endocrine therapy of investigator's choice
干预措施: cyclophosphamide (Drug)
Arm B: Placebo combined with neoadjuvant CT and then adjuvant ET
Nivolumab placebo with paclitaxel followed by nivolumab placebo with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then adjuvant (post-surgery) endocrine therapy of investigator's choice
干预措施: Endocrine Therapy (Drug)
Arm B: Placebo combined with neoadjuvant CT and then adjuvant ET
Nivolumab placebo with paclitaxel followed by nivolumab placebo with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then adjuvant (post-surgery) endocrine therapy of investigator's choice
干预措施: Surgery (Procedure)
结局指标
主要结局
Pathological Complete Response (pCR) Rate
时间窗: Up to approximately 37 months
pCR rate is defined as the percentage of participants who achieved pCR. pCR is defined as no invasive residual disease in breast and lymph nodes performed by a local pathologist. Criteria for evaluation of pCR includes the following: pCR in breast, axillary lymph nodes and non-axillary sentinel node; no histologic evidence of invasive tumor cells; and pCR in the breast.
次要结局
- Pathological Complete Response (pCR) Rate (PD-L1 >=1%)(Up to approximately 37 months)
- Number of Participants With Residual Cancer Burden (RCB)(Up to approximately 37 months)
- Number of Participants With Residual Cancer Burden (RCB) PD-L1 >=1%(Up to approximately 37 months)
- Number of Participants With Adverse Events (AEs)(From first dose to 30 days post last dose of neoadjuvant or adjuvant study therapy (Up to approximately 19 months))
- Number of Participants With Serious Adverse Events (SAEs)(From first dose to 30 days post last dose of neoadjuvant or adjuvant study therapy (Up to approximately 19 months))
- Number of Participants Who Died(Up to approximately 41 months)