Patients With High-risk, Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Primary Breast Cancer MedDRA version: 21.1 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10061020 Term: Breast cancer male System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts a
Conditions
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Localized invasive breast ductal carcinoma, confirmed by the local pathologist, that includes either T1c (tumor size = 2cm)-T2 (tumor size > 2 cm), clinical node stage N1-N2, or T3-T4 clinical node stage N0-N2. Axillary lymph node status must be assessed by fine needle biopsy or core biopsy if there is suspicion for positive axillary lymph node(s)radiographically -ER+ breast cancer 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 -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 Other protocol-defined inclusion criteria apply Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1122 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 748
Exclusion criteria
Exclusion criteria: -Who is 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 7 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 costimulation 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 Other protocol-defined exclusion criteria apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To compare efficacy of nivolumab plus chemotherapy vs nivolumab placebo plus chemotherapy as neoadjuvant treatment in terms of the absence of residual tumor disease in participants with untreated, high-risk ER+, HER2- Breast Cancer. -To compare efficacy of nivolumab vs nivolumab placebo in combination with neoadjuvant chemotherapy and adjuvant ET in terms of EFS in participants with untreated, high-risk ER+, HER2- Breast Cancer.;Secondary Objective: - To assess the efficacy of nivolumab vs nivolumab placebo in combination with neoadjuvant chemotherapy and adjuvant ET in terms of survival -To assess the efficacy of nivolumab vs nivolumab placebo in combination with neoadjuvant chemotherapy in terms of the presence of residual disease -To evaluate the safety and tolerability of nivolumab vs nivolumab placebo in combination with neoadjuvant chemotherapy -To assess change from baseline in global health status/QOL between nivolumab plus chemotherapy vs nivolumab placebo plus chemotherapy - To evaluate change from baseline in physical functioning between nivolumab plus chemotherapy vs nivolumab placebo plus chemotherapy;Primary end point(s): • Pathological complete response (pCR) rate using definition of ypT0/is ypN0) • Event-free survival (EFS) ;Timepoint(s) of evaluation of this end point: • pCR: approximately 7 months • EFS: up to 10 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1/ Overall Survival (OS) 2/ Disease-free Survival (DFS) 3/ Distant Metastasis-free survival (DMFS) 4/ Pathological Complete Response (pCR) using the definition of ypT0 ypN0 5/Pathological Complete Response (pCR) rate using the definition of ypT0/is 6/ Objective response rate (ORR) using definition of tumor response rate per radiologic-based assessment 7/ Objective response rate (ORR) using definition of tumor response rate per clinic-based physical assessment 8/ Residual cancer burden (RCB) category status (0, I, II, III) 9/ Incidence of adverse events (AEs) 10/ Severity of adverse events (AEs) 11/ Change from baseline on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) global health status/quality of life (QOL) subscale (items 29 and 30) 12/ Change from baseline on the EORTC QLQ-C30 physical functioning subscale (items 1 to 5) ;Timepoint(s) of evaluation of this end point: 1/ up to 10 years 2/ up to 10 years 3/ up to 10 years 4/ approximately 7 months 5/ approximately 7 months 6/ approximately 7 months 7/ approximately 7 months 8/ approximately 7 months 9/ approximately 17 months 10/ approximately 17 months 11/ up to 52 weeks 12/ up to 52 weeks | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Czechia, Czech Republic, Denmark, Finland, France, Germany, Hong Kong, Ireland, Italy, Korea, Republic of, Mexico, Netherlands, New Zealand, Poland, Portugal, Romania, Russian Federation, Singapore, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactHead of the GSM-CT
Bristol-Myers Squibb International Corporation
Outcome results
None listed