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.
Recruiting
Phase 3
| Drug | Synonyms | Arms |
|---|---|---|
| nivolumab | Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET | |
| paclitaxel (PTX) | Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET | |
| anthracycline | Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET | |
| cyclophosphamide | Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET | |
| Endocrine Therapy | Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET |
| Name | Type | Description | Interventions |
|---|---|---|---|
| Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET | Experimental | 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 adjuvant ET | Placebo Comparator | Nivolumab placebo with paclitaxel followed by nivolumab placebo with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then nivolumab placebo with adjuvant (post-surgery) endocrine therapy of investigator's choice |
|
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please
visit www.BMSStudyConnect.com
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Pathological Complete response (pCR) Using the definition of ypT0/is ypN0 |
| Time Frame: | approximately 7 months |
| Safety Issue: | |
| Description: |
| Measure: | Overall Survival (OS) |
| Time Frame: | up to 10 years |
| Safety Issue: | |
| Description: |
| Measure: | Disease-free Survival (DFS) |
| Time Frame: | up to 10 years |
| Safety Issue: | |
| Description: |
| Measure: | Distant Metastasis-free survival (DMFS) |
| Time Frame: | up to 10 years |
| Safety Issue: | |
| Description: |
| Measure: | pCR using the definition of ypT0 ypN0 |
| Time Frame: | approximately 7 months |
| Safety Issue: | |
| Description: |
| Measure: | pCR rate using the definition of ypT0/is |
| Time Frame: | approximately 7 months |
| Safety Issue: | |
| Description: |
| Measure: | Objective response rate (ORR) using definition of tumor response rate per radiologic-based assessment |
| Time Frame: | approximately 7 months |
| Safety Issue: | |
| Description: |
| Measure: | ORR using definition of tumor response rate per clinic-based physical assessment |
| Time Frame: | approximately 7 months |
| Safety Issue: | |
| Description: |
| Measure: | Residual cancer burden (RCB) category status (0, I, II, III) |
| Time Frame: | approximately 7 months |
| Safety Issue: | |
| Description: |
| Measure: | Incidence of adverse events (AEs) |
| Time Frame: | approximately 17 months |
| Safety Issue: | |
| Description: |
| Measure: | Severity of AEs |
| Time Frame: | approximately 17 months |
| Safety Issue: | |
| Description: |
| Measure: | 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) |
| Time Frame: | up to 52 weeks |
| Safety Issue: | |
| Description: |
| Measure: | Change from baseline on the EORTC QLQ-C30 physical functioning subscale (items 1 to 5) |
| Time Frame: | up to 52 weeks |
| Safety Issue: | |
| Description: |
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Bristol-Myers Squibb |
August 18, 2021
