Study of Nivolumab Versus Placebo in Combination With Neoadjuvant Chemotherapy and Adjuvant Endocrine Therapy in Participants With High-risk, Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Primary Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Other: nivolumab placeboDrug: anthracyclineDrug: Endocrine TherapyProcedure: Surgery
- Registration Number
- NCT04109066
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 521
- 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-cN2. 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: Placebo combined with neoadjuvant CT and then adjuvant ET paclitaxel (PTX) 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 Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET paclitaxel (PTX) 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 Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET nivolumab 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 Arm B: Placebo combined with neoadjuvant CT and then adjuvant ET Surgery 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 Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET Surgery 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 Arm B: Placebo combined with neoadjuvant CT and then adjuvant ET nivolumab placebo 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 Arm B: Placebo combined with neoadjuvant CT and then adjuvant ET anthracycline 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 Arm B: Placebo combined with neoadjuvant CT and then adjuvant ET Endocrine Therapy 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 Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET anthracycline 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 Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET Endocrine Therapy 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 Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET cyclophosphamide 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 Arm B: Placebo combined with neoadjuvant CT and then adjuvant ET cyclophosphamide 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
- Primary Outcome Measures
Name Time Method Pathological Complete Response (pCR) Rate 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.
- Secondary Outcome Measures
Name Time Method Pathological Complete Response (pCR) Rate (PD-L1 >=1%) 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.
Number of Participants With Residual Cancer Burden (RCB) Up to approximately 37 months RCB is estimated from routine pathologic sections of the primary breast tumor site and the regional lymph nodes after the completion of neoadjuvant therapy. RCB is categorized into the following 4 classes: RCB-0: no residual disease; RCB-1: minimal residual disease; RCB-II: moderate residual disease; RCB-III: and extensive residual disease.
Number of Participants With Residual Cancer Burden (RCB) PD-L1 >=1% Up to approximately 37 months RCB is estimated from routine pathologic sections of the primary breast tumor site and the regional lymph nodes after the completion of neoadjuvant therapy. RCB is categorized into the following 4 classes: RCB-0: no residual disease; RCB-1: minimal residual disease; RCB-II: moderate residual disease; RCB-III: and extensive residual disease.
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 any grade adverse events (AEs). An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment that does not necessarily have a causal relation with this treatment. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
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 with any grade serious adverse events (SAE). SAE is defined as any untoward medical occurrence that, at any dose: Results in death; is life threatening; requires inpatient hospitalization; results in persistent or significant disability; is a congenital anomaly/birth defect. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Number of Participants Who Died Up to approximately 41 months Number of participants who died due to any cause.
Trial Locations
- Locations (232)
Local Institution - 0136
🇺🇸Mobile, Alabama, United States
Local Institution - 0052
🇺🇸Greenbrae, California, United States
Local Institution - 0051
🇺🇸Whittier, California, United States
Local Institution - 0182
🇺🇸Stamford, Connecticut, United States
Local Institution - 0150
🇺🇸Jacksonville, Florida, United States
Local Institution - 0097
🇺🇸Miami, Florida, United States
Local Institution - 0149
🇺🇸Pensacola, Florida, United States
Local Institution - 0120
🇺🇸Tallahassee, Florida, United States
Local Institution - 0054
🇺🇸Athens, Georgia, United States
Local Institution - 0107
🇺🇸Atlanta, Georgia, United States
Scroll for more (222 remaining)Local Institution - 0136🇺🇸Mobile, Alabama, United States