Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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
  • Biological: nivolumab
    Specified Dose on Specified days
  • Drug: paclitaxel (PTX)
    Specified dose on Specified days
  • Drug: anthracycline
    Specified dose on Specified days
  • Drug: cyclophosphamide
    Specified dose on Specified days
  • Drug: Endocrine Therapy
    Variable endocrine therapy of investigators choice
  • Procedure: Surgery
    Surgery for breast cancer
Placebo Comparator
Arm B: Placebo combined with neoadjuvant CT and adjuvant ET
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
  • Drug: paclitaxel (PTX)
    Specified dose on Specified days
  • Other: nivolumab placebo
    Specified dose on Specified days
  • Drug: anthracycline
    Specified dose on Specified days
  • Drug: cyclophosphamide
    Specified dose on Specified days
  • Drug: Endocrine Therapy
    Variable endocrine therapy of investigators choice
  • Procedure: Surgery
    Surgery for breast cancer

Recruiting Locations

MetroHealth Medical Center
Cleveland, Ohio 44109
Contact:
Ila Tamaskar, Site 0053
216-957-6488

More Details

Status
Recruiting
Sponsor
Bristol-Myers Squibb

Study Contact

Recruiting sites have contact information.Please contact the sites directly. If there is no contact information,
please email:
Clinical.Trials@bms.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.