Neoadjuvant Pembrolizumab + Decitabine Followed by Std Neoadj Chemo for Locally Advanced HER2- Breast Ca

Running, not enrolling · Phase 2

Conditions studied: Breast Adenocarcinoma, Estrogen Receptor- Negative Breast Cancer, Estrogen Receptor-positive Breast Cancer, HER2/Neu Negative, Invasive Breast Carcinoma, Progesterone Receptor Negative, Progesterone Receptor Positive Tumor, Stage II Breast Cancer, Stage IIA Breast Cancer, Stage IIB Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Triple-negative Breast Carcinoma

In brief

This study is a 2-cohort, open-label, multicenter, phase 2 study of a short course of immunotherapy consisting of sequential decitabine followed by pembrolizumab administered prior to a standard neoadjuvant chemotherapy regimen for patients with locally advanced HER2-negative breast cancer. The primary efficacy objective is to determine if the immunotherapy increases the presence and percentage of tumor and/or stromal area of infiltrating lymphocytes prior to initiation of standard neoadjuvant chemotherapy. At enrollment, patients will be assigned to one of 2 cohorts based on hormone receptor status. * Cohort A - patients with HER2-negative, hormone receptor-negative breast cancer (defined as both ER and PgR with \< 10% positive staining on IHC) Note: before beginning standard neoadjuvant chemotherapy, patients in Cohort A may be reassigned to Cohort A2 to receive extended pembrolizumab as part of new standard neoadjuvant and postoperative adjuvant therapy. * Cohort B - patients with HER2-negative, hormone receptor-positive breast cancer (defined as either ER or PgR with ≥ 10% positive staining on IHC)

Key facts

Study ID

NCT02957968

Run by

Virginia Commonwealth University

People needed

46

Starts

2017-01-24

Expected to finish

2027-03-31

Last updated by the study team

2026-07-01

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Invasive adenocarcinoma of the breast diagnosed by core needle biopsy
• Breast cancer determined to be HER2-negative per current American Society of Clinical Oncologists/College of American Pathologists (ASCO/CAP) human epidermal growth factor receptor 2 (HER2) Guidelines (If IHC was performed, IHC 0 or 1+; if fluorescence in situ hybridization (FISH) or other in situ hybridization test, dual probe HER2/Chromosome 17 Centromere (CEP17) ratio < 2.0 with an average HER2 copy number < 4.0 signals/cell)
• Breast cancer determined to be hormone receptor-positive or hormone receptor-negative defined as follows:
• Hormone receptor-positive: ≥ 10% staining by IHC for either estrogen receptor (ER) or progesterone receptor (PgR)
• Hormone receptor-negative: < 10% staining by IHC for both ER and PgR
• Locally advanced breast cancer defined as any of the following per American Joint Committee on Cancer (AJCC) Staging Criteria:
• T2 based on tumor measurements by physical examination or imaging and with clinically positive regional lymph nodes (cN1 or cN2), irrespective of hormone receptor status
• Hormone receptor-negative breast cancer patients with tumor size of 3-5 cm measured by physical examination or imaging with clinically negative regional lymph nodes (cN0)
• Any T3 based on tumor measurements by physical examination or imaging
• Any T4 (including inflammatory breast cancer), irrespective of hormone receptor status
• Ipsilateral axillary lymph nodes must be evaluated by MRI or ultrasound within 12 weeks prior to study registration to determine clinical nodal status. If imaging is suspicious or abnormal, a fine needle aspiration (FNA) or core biopsy of the questionable node(s) on imaging is required. Nodal status should be classified according to the following criteria:
• Nodal status - negative
• Imaging of the axilla is negative; OR
• Imaging of the axilla is suspicious or abnormal AND FNA or core biopsy is negative.
• Nodal status - positive
• FNA or core biopsy of node(s) is cytologically or histologically suspicious or positive
• Breast imaging performed prior to study registration as follows:
• Ipsilateral breast - within 12 weeks
• Contralateral breast - within 24 weeks
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate bone marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1,500/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 10.0 g/dL

You may not qualify if…

• Breast cancer treatment for the currently diagnosed breast cancer including radiation therapy, chemotherapy, targeted therapy, or endocrine therapy prior to study registration
• Administration of a live vaccine within 30 days prior to initiating study treatment Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are permitted; however, intranasal influenza vaccines (eg, Flu-Mist) are live attenuated vaccines, and are not allowed.
• Administration of a monoclonal antibody within 4 weeks prior to initiating study treatment or has not recovered (ie, ≤ grade 1 or at baseline) from adverse events (AEs) due to a monoclonal antibody administered more than 4 weeks earlier
• Administration of any investigational agent within 4 weeks prior to initiating study treatment
• Evidence of metastatic disease that is extensive enough to preclude consideration of subsequent definitive surgery for the primary tumor
• History of ipsilateral invasive breast cancer or ipsilateral ductal carcinoma in situ (DCIS) Note: Patients with history of ipsilateral lobular carcinoma in situ (LCIS) are eligible.
• History of solid organ or allogeneic stem cell transplant
• Previous therapy for any malignancy with an anthracycline or taxane for Cohorts A and B and carboplatin for Cohort A
• Cardiac disease that would preclude administration of the drugs included in the study treatment regimen including, but not limited to:
• Angina pectoris that requires the current use of anti-anginal medication
• Ventricular arrhythmias except for benign premature ventricular contractions
• Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
• Conduction abnormality requiring a pacemaker
• Valvular disease with documented compromise in cardiac function; and symptomatic pericarditis
• Nervous system disorder (ie, paresthesia, peripheral motor neuropathy, or peripheral sensory neuropathy) ≥ grade 2, per CTCAE v5.0
• Administration of or condition requiring administration of systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating study treatment Exception: Patients with conditions that can be managed with steroids equivalent to or less than an oral prednisone dose of 10 mg daily would not be excluded from the study.
• Previous therapy for this cancer with an anti-anti-programmed death-1 (PD-1), anti-PD-L1, anti-PD-L2 agent, or any other immunomodulatory agent
• Known or presumed hypersensitivity to decitabine or pembrolizumab (or any of their excipients)
• Diagnosed immunodeficiency, eg, human immunodeficiency virus (HIV)
• Active autoimmune disease requiring systemic treatment within the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) or a documented history of clinically severe autoimmune disease or a syndrome that requires systemic steroids or immunosuppressive agents Note: Patients with the conditions or medical history listed below are NOT excluded from this study.
• Vitiligo
• Resolved childhood asthma/atopy
• Requirement for intermittent use of bronchodilators or local steroid injections or topical steroids
• Hypothyroidism stable on hormone replacement
• Sjogren's Syndrome

Where it is running

• St. Elizabeth Healthcare — Edgewood, Kentucky, United States
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States
• University of Virginia — Charlottesville, Virginia, United States
• Virginia Commonwealth University/Massey Cancer Center — Richmond, Virginia, United States

Full record on ClinicalTrials.gov

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