Clinical trial · Interventional
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
A Randomized, Multicenter, Double-blind, Placebo-controlled Phase 3 Study of Nivolumab Versus Placebo in Combination With Neoadjuvant Chemotherapy and Adjuvant Endocrine Therapy in Patients With High-risk, Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Primary Breast Cancer
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Breast Cancer | Malignant Breast Neoplasm | CURATED_EXACT | 0.92 |
Interventions
Interventions (7)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| anthracycline | Drug | — | UNRESOLVED |
| cyclophosphamide | Drug | Cyclophosphamide | ALIAS |
| Endocrine Therapy | Drug | Hormone Therapy | ALIAS |
| nivolumab | Biological | Nivolumab | ALIAS |
| nivolumab placebo | Other | — | UNRESOLVED |
| paclitaxel (PTX) | Drug | Paclitaxel | ALIAS |
| Surgery | Procedure | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET
- description
- 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
- interventionNames
- Biological: nivolumab
- Drug: paclitaxel (PTX)
- Drug: anthracycline
- Drug: cyclophosphamide
- Drug: Endocrine Therapy
- Procedure: Surgery
- type
- PLACEBO_COMPARATOR
- label
- Arm B: Placebo combined with neoadjuvant CT and then adjuvant ET
- description
- 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
- interventionNames
- Drug: paclitaxel (PTX)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (2)
- DERIVEDLoi S, Salgado R, Curigliano G, Romero Diaz RI, Delaloge S, Rojas Garcia CI, Kok M, Saura C, Harbeck N, Mittendorf EA, Yardley DA, Suarez Zaizar A, Caminos FR, Ungureanu A, Reinoso-Toledo JG, Guarneri V, Egle D, Ades F, Pacius M, Chhibber A, Chandra R, Nathani R, Spires T, Wu JQ, Pusztai L, McArthur H. Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial. Nat Med. 2025 Feb;31(2):433-441. doi: 10.1038/s41591-024-03414-8. Epub 2025 Jan 21. PMID 39838118
- DERIVEDSchlam I, Corti C, Sammons S, Mittendorf EA, Tolaney SM. Checkpoint inhibition for early-stage hormone receptor-positive breast cancer. Expert Opin Biol Ther. 2024 Jun;24(6):511-520. doi: 10.1080/14712598.2024.2370395. Epub 2024 Jun 24. PMID 38913933