Phase 3
N=521
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
Breast Cancer
Bottom Line
View on ClinicalTrials.gov: NCT04109066 ↗Enrolled (actual)
521
Serious AEs
26.1%
Results posted
Mar 2024
Primary outcome: Primary: Pathological Complete Response (pCR) Rate — 24.5; 13.8 Percentage of participants — p=0.0021
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- nivolumab (Biological); paclitaxel (PTX) (Drug); nivolumab placebo (Other); anthracycline (Drug); cyclophosphamide (Drug); Endocrine Therapy (Drug); Surgery (Procedure)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Bristol-Myers Squibb
- Primary completion
- Jan 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Pathological Complete Response (pCR) Rate |
24.5; 13.8 | 0.0021 sig |
| SECONDARY Pathological Complete Response (pCR) Rate (PD-L1 >=1%) |
44.3; 20.2 | — |
| SECONDARY Number of Participants With Residual Cancer Burden (RCB) |
62; 34; 17; 20; 90; 106 | — |
| SECONDARY Number of Participants With Residual Cancer Burden (RCB) PD-L1 >=1% |
38; 16; 10; 6; 25; 36 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) |
259; 252; 254; 236; 41; 14 | — |
| SECONDARY Number of Participants With Serious Adverse Events (SAEs) |
80; 45 | — |
| SECONDARY Number of Participants Who Died |
15; 8 | — |
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.
Eligibility Criteria
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) 1 tumor in different quadrants of the breast)
- Bilateral invasive BC
Other protocol-defined inclusion/exclusion criteria apply
Data sourced from ClinicalTrials.gov (NCT04109066). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.