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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2016-01980 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| P30CA016059 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
| National Cancer Institute (NCI) | NIH |
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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.
Both cohorts will receive the identical doses and treatment schedules of decitabine and pembrolizumab followed by a standard neoadjuvant chemotherapy regimen. Both cohorts will receive 4 cycles of AC and 12 doses of weekly paclitaxel or Nab-paclitaxel. Paclitaxel or Nab-paclitaxel will be combined with carboplatin for Cohorts A and A2 (TNBC). The sequence of the 2 regimens will be at the discretion of the treating medical oncologist following the safety lead-in phase. For the primary endpoint, Cohorts A and A2 will be evaluated together, separate from Cohort B.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A: Triple Negative Breast Cancer (TNBC) | Experimental | Triple Negative Breast Cancer (Cohort A): Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin. |
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| Cohort B: HER2-negative hormone receptor-positive tumors | Experimental | HER2-negative hormone receptor-positive tumors (Cohort B): Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel. |
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| Cohort A2: Triple Negative Breast Cancer (TNBC) with Extended Pembrolizumab | Experimental | Triple Negative Breast Cancer (Cohort A2). Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin, and pembrolizumab every 3 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Doxorubicin | Drug | 60 mg/m2 once every 2 weeks for 4 cycles. |
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| Measure | Description | Time Frame |
|---|---|---|
| The Percentage of Increase in Tumor and Stroma With Infiltrating Lymphocytes (TIL) From Baseline Pre-treatment Biopsy to Post-immunotherapy Biopsy Following Administration of Decitabine Followed by Pembrolizumab. | To determine and quantify if treatment with neoadjuvant decitabine followed by pembrolizumab increases lymphocyte infiltration into tumor and/or stroma in patients with locally advanced, HER2-negative breast cancer. | Baseline pre-treatment biopsy to post-immunotherapy biopsy following administration of decitabine followed by pembrolizumab, 3-7 day window after Day 22 medication administration, about one month |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Adverse Events (AEs) Reported During and After Immune Treatment (ie, Decitabine and Pembrolizumab) | Using criteria in the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0), all adverse events (AEs) regardless of grade or attribution, will be captured from the beginning of study treatment (initiation of decitabine) until initiation of standard neoadjuvant chemotherapy. For patients who do not initiate pembrolizumab, all AEs will be captured until 30 days following the last dose of decitabine or until another cancer treatment is initiated, whichever occurs first.For patients who initiate pembrolizumab, immune related adverse events (irAEs) (clinically significant and non-clinically significant) will be captured from the initiation of pembrolizumab through the end of the 30- day post-surgery (or post-treatment, for those who don't have surgery) follow-up period and at a 12-month follow-up time point. |
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Inclusion Criteria:
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:
Locally advanced breast cancer defined as any of the following per American Joint Committee on Cancer (AJCC) Staging Criteria:
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
Nodal status - 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:
Adequate renal function as defined below:
Serum creatinine ≤ upper limit of normal (ULN) for the lab or a calculated creatinine clearance ≥ 60 mL/min
Adequate hepatic function as defined below:
Left ventricular ejection fraction (LVEF) assessment (ie, 2-D echocardiogram or multigated acquisition (MUGA) scan) performed within 12 weeks prior to study registration indicates an LVEF ≥ 50% regardless of the cardiac imaging facility's lower limit of normal
Women who are not postmenopausal or have not undergone hysterectomy must have a documented negative serum pregnancy test within 72 hours prior to initiating study treatment.
Note: Postmenopausal is defined as any of the following:
Age ≥ 60 years
Age < 60 years and amenorrheic for at least 1 year with follicle-stimulating hormone (FSH) and plasma estradiol levels in the postmenopausal range
Bilateral oophorectomy
Exclusion Criteria:
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:
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.
Known history or evidence of interstitial lung disease or active, non-infectious pneumonitis
Known history of active bacillus tuberculosis (TB)
Active infection requiring systemic therapy
Known active Hepatitis B or C
Pregnancy or breastfeeding
Diagnosis or treatment for another malignancy within 5 years prior to study registration, with the following exceptions: complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, any in situ malignancy, and low-risk prostate cancer after curative therapy
Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements
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| Name | Affiliation | Role |
|---|---|---|
| Harry D. Bear, M.D., Ph.D. | Massey Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. Elizabeth Healthcare | Edgewood | Kentucky | 41017 | United States | ||
| Ohio State University Comprehensive Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40021215 | Background | Bear HD, Deng X, Bandyopadhyay D, Idowu M, Jenkins TM, Kmieciak M, Williams M, Archer G, Gwaltney L, Dillon P, Flora D, Stover D, Poklepovic AS, Hackney M, Ross M, Vachhani H, Louie R, McGuire KP, Grover A, Rahman T, Hendrix A. T-cell immune checkpoint inhibition plus hypomethylation for locally advanced HER2-negative breast cancer: a phase 2 neoadjuvant window trial of decitabine and pembrolizumab followed by standard neoadjuvant chemotherapy. J Immunother Cancer. 2025 Feb 27;13(2):e010294. doi: 10.1136/jitc-2024-010294. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort A: Triple Negative Breast Cancer (TNBC) | Triple Negative Breast Cancer (Cohort A): Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin IV area under curve ( AUC) 1.5 once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 22, 2020 |
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| Cyclophosphamide | Drug | cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. |
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| Paclitaxel | Drug | Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. |
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| Carboplatin | Drug | carboplatin IV 1.5 area under curve (AUC) once weekly for 12 weeks. |
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| Decitabine | Drug | Given IV |
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| Pembrolizumab | Drug | Given IV |
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| Time of study registration until 30 days following the end of administration of decitabine and pembrolizumab, or until another cancer treatment was initiated, or 30 days following surgery, 12- months. |
| Number of Patients Meeting Criteria for Lymphocyte-predominant Breast Cancer (LPBC) Following Treatment With Decitabine and Pembrolizumab | To determine if the study treatment increases the proportion of tumors with ≥ 60% tumor or stromal area infiltrated with lymphocytes (ie, LPBC). The percentage of patients meeting criteria for LPBC following treatment with decitabine and pembrolizumab compared to the percentage before treatment (LPBC is defined as breast cancer with ≥ 60% intratumoral or stromal area with infiltrating lymphocytes.) | Assessed at end of administration of decitabine and pembrolizumab Day- Window of time Days 25-29 |
| Number of Patients With Pathologic Complete Response (pCR) in the Breast and Post-therapy Lymph Nodes. | To determine the rate of pCR in the breast and lymph nodes (pCR breast and nodes). The number of patients with pCR in the breast and post-therapy lymph nodes defined as the absence of any invasive cancer in the resected breast specimen and absence of cancer on H&E evaluation of all resected lymph nodes following completion of neoadjuvant therapy (ypT0/is; ypN0). | End of administration of decitabine and pembrolizumab Day- Window of time Days 25-29, or 30 days following surgery |
| Number of Patients With no or Minimal Residual Disease in the Resected Breast and Axillary Specimen. | To determine the rate of Residual Cancer Burden (RCB) Index value of 0-1 following all neoadjuvant therapy. The number of patients with no (0) or (i) minimal residual disease in the resected breast and axillary specimen defined as RCB Index value 0 or i (Arabic numeral). | End of therapy surgery |
| The Number of Patients With Clinical Complete Response (cCR) | To determine the rate of clinical complete response in the breast and lymph nodes (cCR breast and nodes) following all neoadjuvant therapy. The proportion of patients with cCR defined as the absence of tumor based on physical examination of the breast and nodes following completion of all neoadjuvant therapy. | End of therapy surgery |
| Enumeration of T Cells and Immune Cell Subsets | To characterize the alteration of T lymphocyte and other host cell infiltration and immune response gene signatures in breast cancers resulting from treatment with decitabine and pembrolizumab. Enumeration of T cells and immune cell subsets, including cluster of differentiation 8 (CD8)+ cytotoxic T cells, cluster of differentiation 4 (CD4)+ helper T cells, FOXP3+ regulatory T Cells, cluster of differentiation 20 (CD20)+ B cells, and MDSC in the tumor sample procured by core needle biopsy following completion of sequential decitabine followed by pembrolizumab compared to the number of these cells in tumor samples procured at baseline. | Assessed at end of administration of decitabine and pembrolizumab Day- Window of time Days 25-29 |
| Evaluation of Expression of Protein Programmed Death-Ligand 1 (PD-L1) Within Tumor, Stroma, and Infiltrating Immune Cells Combined, at Baseline and Following Immunotherapy. | To evaluate the correlation of pre-existing and post-immunotherapy immune response signatures with response to neoadjuvant chemotherapy. The number of PD-L1 positive cells (including tumor cells, lymphocytes, and macrophages) divided by the total number of tumor cells (PD-L1 positive or negative) in an area. | Assessed at end of administration of decitabine and pembrolizumab Day- Window of time Days 25-29 |
| Change of Intensity of Programmed Death-Ligand 1 (PD-L1) Expression by Assay as it Relates to Pathologic Complete Response (pCR) Rates From Chemotherapy | Combined positive score (CPS) is calculated by the number of PD-L1 positive cells, including tumor cells, lymphocytes, and macrophages divided by the total number of viable tumor cells multiplied by 100 (n>100 is possible). The point biserial correlation coefficient (RPB) was calculated to quantify the association between the binary factor (BFA) pCR,and continuous factor PD-L1-CPS. The two PD-L1-cps variables (BX2_PD-L1_cps, Change_PD-L1_cps) were considered separately. | Baseline biopsy (BX1) before treatment, end of therapy (EOT) surgery 2nd core biopsy (BX2) 3-7 days following last dose of pre-chemotherapy pembrolizumab (i.e after the second dose of pembrolizumab) |
| Change of Intensity of PD-L1 Expression by Assay as it Relates to Pathologic Complete Response pCR Rates From Chemotherapy Tumor Samples for Proprietary PD-L1 Staining. | A semi-quantitative method used to assess the expression level of proteins or other markers in tissue samples, particularly in immunohistochemistry (IHC) studies. It helps to determine the intensity and proportion of staining, providing a numerical representation of biomarker abundance. The H-score is calculated by multiplying the percentage of positive cells by their staining intensity and summing these values, as described in Dolled-Filhart et al, which calculates a score based on intensity of tumor staining and the percentage of cells implemented. Point Biserial correlation coefficient (RPB) was calculated to quantify the association between the binary factor pCR, and continuous factor PDL-1-Hscore.The PD-L1-Hscore variables (BX2_PD-L1_Hscore, Change_PD-L1_Hscore) were considered separately. | Baseline biopsy (BX1) prior to therapy, EOT surgery 2nd core biopsy (BX2) 3-7 days following last dose of pre-chemotherapy pembrolizumab |
| Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-decitabine Compared to MDSC Found in Blood Samples Collected at Baseline. | Evaluate the level of circulating MDSC per ml of blood at baseline, following treatment with decitabine alone. | Assessed at end of administration of decitabine compared to assessment at baseline prior to protocol treatments. |
| Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-pembrolizumab Compared to MDSC Found in Blood Samples Collected at Baseline. | Evaluate the level of circulating MDSC per ml of blood at baseline, following treatment with decitabine, and following treatment with decitabine and 2 doses of pembrolizumab. | Assessed at baseline, after administration of decitabine, after decitabine and 2 doses of pembrolizumab. |
| Event Free Survival (EFS) Rate at 12 Months Following the Last Dose of Pembrolizumab. | Number of patients who are alive and have not had disease relapse at 12 months following last dose of pembrolizumab | 12 Months following surgery |
| Columbus |
| Ohio |
| 43210 |
| United States |
| University of Virginia | Charlottesville | Virginia | 22903 | United States |
| Virginia Commonwealth University/Massey Cancer Center | Richmond | Virginia | 23298 | United States |
| FG001 | Cohort B: HER2-negative Hormone Receptor-positive Tumors | Human epidermal growth factor receptor 2 (HER2)-negative hormone receptor-positive tumors (Cohort B): Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
| FG002 | Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab | Triple Negative Breast Cancer (Cohort A2). Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin, and pembrolizumab every 3 weeks. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin AUC 1.5 once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort A: Triple Negative Breast Cancer (TNBC) | Triple Negative Breast Cancer (Cohort A): Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin AUC 1.5 once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
| BG001 | Cohort B: HER2-negative Hormone Receptor-positive Tumors | HER2-negative hormone receptor-positive tumors (Cohort B): Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
| BG002 | Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab | Triple Negative Breast Cancer (Cohort A2). Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin, and pembrolizumab every 3 weeks. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin AUC 1.5 once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Median | Full Range | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||
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| Primary | The Percentage of Increase in Tumor and Stroma With Infiltrating Lymphocytes (TIL) From Baseline Pre-treatment Biopsy to Post-immunotherapy Biopsy Following Administration of Decitabine Followed by Pembrolizumab. | To determine and quantify if treatment with neoadjuvant decitabine followed by pembrolizumab increases lymphocyte infiltration into tumor and/or stroma in patients with locally advanced, HER2-negative breast cancer. | Posted | Mean | Standard Deviation | % of stromal area occupied by TIL | Baseline pre-treatment biopsy to post-immunotherapy biopsy following administration of decitabine followed by pembrolizumab, 3-7 day window after Day 22 medication administration, about one month |
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| Secondary | Number of Adverse Events (AEs) Reported During and After Immune Treatment (ie, Decitabine and Pembrolizumab) | Using criteria in the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0), all adverse events (AEs) regardless of grade or attribution, will be captured from the beginning of study treatment (initiation of decitabine) until initiation of standard neoadjuvant chemotherapy. For patients who do not initiate pembrolizumab, all AEs will be captured until 30 days following the last dose of decitabine or until another cancer treatment is initiated, whichever occurs first.For patients who initiate pembrolizumab, immune related adverse events (irAEs) (clinically significant and non-clinically significant) will be captured from the initiation of pembrolizumab through the end of the 30- day post-surgery (or post-treatment, for those who don't have surgery) follow-up period and at a 12-month follow-up time point. | Posted | Number | Adverse Events Reported | Time of study registration until 30 days following the end of administration of decitabine and pembrolizumab, or until another cancer treatment was initiated, or 30 days following surgery, 12- months. |
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| Secondary | Number of Patients Meeting Criteria for Lymphocyte-predominant Breast Cancer (LPBC) Following Treatment With Decitabine and Pembrolizumab | To determine if the study treatment increases the proportion of tumors with ≥ 60% tumor or stromal area infiltrated with lymphocytes (ie, LPBC). The percentage of patients meeting criteria for LPBC following treatment with decitabine and pembrolizumab compared to the percentage before treatment (LPBC is defined as breast cancer with ≥ 60% intratumoral or stromal area with infiltrating lymphocytes.) | Posted | Count of Participants | Participants | Assessed at end of administration of decitabine and pembrolizumab Day- Window of time Days 25-29 |
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| Secondary | Number of Patients With Pathologic Complete Response (pCR) in the Breast and Post-therapy Lymph Nodes. | To determine the rate of pCR in the breast and lymph nodes (pCR breast and nodes). The number of patients with pCR in the breast and post-therapy lymph nodes defined as the absence of any invasive cancer in the resected breast specimen and absence of cancer on H&E evaluation of all resected lymph nodes following completion of neoadjuvant therapy (ypT0/is; ypN0). | All participants in trial either did not have surgery performed, or did not have a suitable biopsy, therefore pathological response could not be assessed for all participants. | Posted | Count of Participants | Participants | End of administration of decitabine and pembrolizumab Day- Window of time Days 25-29, or 30 days following surgery |
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| Secondary | Number of Patients With no or Minimal Residual Disease in the Resected Breast and Axillary Specimen. | To determine the rate of Residual Cancer Burden (RCB) Index value of 0-1 following all neoadjuvant therapy. The number of patients with no (0) or (i) minimal residual disease in the resected breast and axillary specimen defined as RCB Index value 0 or i (Arabic numeral). | All participants in trial either did not have surgery performed, or did not have a suitable biopsy, therefore pathological response could not be assessed for all participants. | Posted | Count of Participants | Participants | End of therapy surgery |
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| Secondary | The Number of Patients With Clinical Complete Response (cCR) | To determine the rate of clinical complete response in the breast and lymph nodes (cCR breast and nodes) following all neoadjuvant therapy. The proportion of patients with cCR defined as the absence of tumor based on physical examination of the breast and nodes following completion of all neoadjuvant therapy. | Posted | Count of Participants | Participants | End of therapy surgery |
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| Secondary | Enumeration of T Cells and Immune Cell Subsets | To characterize the alteration of T lymphocyte and other host cell infiltration and immune response gene signatures in breast cancers resulting from treatment with decitabine and pembrolizumab. Enumeration of T cells and immune cell subsets, including cluster of differentiation 8 (CD8)+ cytotoxic T cells, cluster of differentiation 4 (CD4)+ helper T cells, FOXP3+ regulatory T Cells, cluster of differentiation 20 (CD20)+ B cells, and MDSC in the tumor sample procured by core needle biopsy following completion of sequential decitabine followed by pembrolizumab compared to the number of these cells in tumor samples procured at baseline. | Not Posted | Dec 2026 | Assessed at end of administration of decitabine and pembrolizumab Day- Window of time Days 25-29 | Participants | |||||||||||||||||||||||||||||||||||||
| Secondary | Evaluation of Expression of Protein Programmed Death-Ligand 1 (PD-L1) Within Tumor, Stroma, and Infiltrating Immune Cells Combined, at Baseline and Following Immunotherapy. | To evaluate the correlation of pre-existing and post-immunotherapy immune response signatures with response to neoadjuvant chemotherapy. The number of PD-L1 positive cells (including tumor cells, lymphocytes, and macrophages) divided by the total number of tumor cells (PD-L1 positive or negative) in an area. | Not all participants had surgery performed, therefore response could not be assessed for all patients (3/36). Specimen issues limited number who could have PD-L1 assessments to 37/46 | Posted | Mean | Standard Deviation | Number of PD-L1 positive cells | Assessed at end of administration of decitabine and pembrolizumab Day- Window of time Days 25-29 |
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| Secondary | Change of Intensity of Programmed Death-Ligand 1 (PD-L1) Expression by Assay as it Relates to Pathologic Complete Response (pCR) Rates From Chemotherapy | Combined positive score (CPS) is calculated by the number of PD-L1 positive cells, including tumor cells, lymphocytes, and macrophages divided by the total number of viable tumor cells multiplied by 100 (n>100 is possible). The point biserial correlation coefficient (RPB) was calculated to quantify the association between the binary factor (BFA) pCR,and continuous factor PD-L1-CPS. The two PD-L1-cps variables (BX2_PD-L1_cps, Change_PD-L1_cps) were considered separately. | Positive RPB indicates a positive relationship between the BFA pCR and continuous factor PDL-1-CPS as values of BFA pCR increase, the value of the continuous factor PDL-1-CPS tends to increase. The positive RPB means that pCR patient group tends to have larger PDL-1-CPS score. The negative RPB indicates an inverse relationship between the binary factor pCR and continuous factor PDL-1-cps. The negative RPB indicates pCR patient group tends to have lower PDL-1-cps score. | Posted | Number | 95% Confidence Interval | Corr. Coefficient pCR & PD-L1 CPS | Baseline biopsy (BX1) before treatment, end of therapy (EOT) surgery 2nd core biopsy (BX2) 3-7 days following last dose of pre-chemotherapy pembrolizumab (i.e after the second dose of pembrolizumab) | Tumor Biopsies | Tumor Biopsies |
| ||||||||||||||||||||||||||||||||
| Secondary | Change of Intensity of PD-L1 Expression by Assay as it Relates to Pathologic Complete Response pCR Rates From Chemotherapy Tumor Samples for Proprietary PD-L1 Staining. | A semi-quantitative method used to assess the expression level of proteins or other markers in tissue samples, particularly in immunohistochemistry (IHC) studies. It helps to determine the intensity and proportion of staining, providing a numerical representation of biomarker abundance. The H-score is calculated by multiplying the percentage of positive cells by their staining intensity and summing these values, as described in Dolled-Filhart et al, which calculates a score based on intensity of tumor staining and the percentage of cells implemented. Point Biserial correlation coefficient (RPB) was calculated to quantify the association between the binary factor pCR, and continuous factor PDL-1-Hscore.The PD-L1-Hscore variables (BX2_PD-L1_Hscore, Change_PD-L1_Hscore) were considered separately. | Positive RPB indicates a positive relationship between the binary factor pCR and continuous factor PDL-1-Hscore. As the binary factor pCR value increases, the value of the continuous factor PDL-1-Hscore also tends to increase. The positive RPB means that pCR patient group tends to have higher PDL-1-Hscore. A negative RPB indicates an inverse relationship between the binary factor pCR and continuous factor PDL-1-Hscore, a negative RPB indicates pCR patient group tends to have lower PDL-1-Hscore. | Posted | Number | 95% Confidence Interval | Corr. Coefficient pCR & PD-L1 H-Score | Baseline biopsy (BX1) prior to therapy, EOT surgery 2nd core biopsy (BX2) 3-7 days following last dose of pre-chemotherapy pembrolizumab | Tumor Biopsies | Tumor Biopsies |
| ||||||||||||||||||||||||||||||||
| Secondary | Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-decitabine Compared to MDSC Found in Blood Samples Collected at Baseline. | Evaluate the level of circulating MDSC per ml of blood at baseline, following treatment with decitabine alone. | Posted | Mean | Standard Deviation | absolute cell count per ml of blood | Assessed at end of administration of decitabine compared to assessment at baseline prior to protocol treatments. |
| |||||||||||||||||||||||||||||||||||
| Secondary | Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-pembrolizumab Compared to MDSC Found in Blood Samples Collected at Baseline. | Evaluate the level of circulating MDSC per ml of blood at baseline, following treatment with decitabine, and following treatment with decitabine and 2 doses of pembrolizumab. | Posted | Mean | Standard Deviation | Absolute cell count per ml of blood | Assessed at baseline, after administration of decitabine, after decitabine and 2 doses of pembrolizumab. |
| |||||||||||||||||||||||||||||||||||
| Secondary | Event Free Survival (EFS) Rate at 12 Months Following the Last Dose of Pembrolizumab. | Number of patients who are alive and have not had disease relapse at 12 months following last dose of pembrolizumab | Patients who did not have surgery due to disease progression or experienced disease progression before undergoing surgery were excluded. | Posted | Count of Participants | Participants | 12 Months following surgery |
|
Adverse event data was collected from time of study registration until 30 days following the last dose of decitabine, or until another cancer treatment was initiated, or 30 days following surgery, 12- months.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort A: Triple Negative Breast Cancer (TNBC) | Triple Negative Breast Cancer (Cohort A): Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin AUC 1.5 once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV | 3 | 21 | 7 | 21 | 21 | 21 |
| EG001 | Cohort B: HER2-negative Hormone Receptor-positive Tumors | HER2-negative hormone receptor-positive tumors (Cohort B): Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV | 0 | 18 | 6 | 18 | 18 | 18 |
| EG002 | Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab | Triple Negative Breast Cancer (Cohort A2). Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin, and pembrolizumab every 3 weeks. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin AUC 1.5 once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV | 0 | 7 | 4 | 7 | 7 | 7 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Adrenal Insufficiency | Endocrine disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Blood and Lymphatic System Disorders- Other | Blood and lymphatic system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Catheter Related Infection | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| Creatinine Increased | Investigations | CTCAE v 5.0 | Systematic Assessment |
| |
| Dental Caries | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Disease Progression | General disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Esophageal Infection | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| Febrile Neutropenia | Blood and lymphatic system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Fever | General disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Gallbladder Infection | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| General Disorders and Administration Site Conditions- Other | General disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Guillain-Barre syndrome | Nervous system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Hyponatremia | Metabolism and nutrition disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Infections and Infestations- Other | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| Lung Infection | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| Lipase Increased | Investigations | CTCAE v 5.0 | Systematic Assessment |
| |
| Muscle Weakness Lower Limb | Musculoskeletal and connective tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Pain in Extremity | Musculoskeletal and connective tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Platelet Count Decreased | Investigations | CTCAE v 5.0 | Systematic Assessment |
| |
| Rash Maculo-Papular | Skin and subcutaneous tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| Sinus Bradycardia | Cardiac disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Sinus Tachycardia | Cardiac disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Small Intestinal Obstruction | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Thromboembolic Event | Vascular disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Tooth Infection | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| Vascular Disorders- Other | Vascular disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Vasculitis | Vascular disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Adrenal Insufficiency | Endocrine disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Alanine Aminotransferase Increased | Investigations | CTCAE v 5.0 | Systematic Assessment |
| |
| Alkaline Phosphatase Increased | Investigations | CTCAE v 5.0 | Systematic Assessment |
| |
| Allergic Reaction | Immune system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Allergic Rhinitis | Respiratory, thoracic and mediastinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Asparate Aminotransferase Increased | Investigations | CTCAE v 5.0 | Systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Bloating | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Blood Bilirubin Increased | Investigations | CTCAE v 5.0 | Systematic Assessment |
| |
| Bone Pain | Musculoskeletal and connective tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Breast Pain | Reproductive system and breast disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Bruising | Injury, poisoning and procedural complications | CTCAE v 5.0 | Systematic Assessment |
| |
| Cardiac Disorders-Other | Cardiac disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Catheter Related Infection | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| Chills | General disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Cholesterol High | Investigations | CTCAE v 5.0 | Systematic Assessment |
| |
| Chronic Kidney Disease | Renal and urinary disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Creatinine Increased | Investigations | CTCAE v 5.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Dental Carries | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Disease Progression | General disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Dry Eye | Eye disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Dry Mouth | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Ear Pain | Ear and labyrinth disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Edema Face | General disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Edema Limbs | General disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Eosinophilia | Blood and lymphatic system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Esophageal Infection | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| Fatigue | General disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Febrile Neutropenia | Blood and lymphatic system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Fever | General disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Flu Like Symptoms | General disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Gait Disturbance | General disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Gallbladder Infection | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| Gastroesophageal Reflux Disease | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Gastrointestinal Disorders- Other | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| General Disorders Administration Site Conditions | General disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Guillain-Barre Syndrome | Nervous system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Hot Flashes | Vascular disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Hyponatremia | Metabolism and nutrition disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Hypoparathyroidism | Endocrine disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Infections and infestations - Other | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| Injury, poisoning and procedural complications - Other | Injury, poisoning and procedural complications | CTCAE v 5.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Investigations- Other | Investigations | CTCAE v 5.0 | Systematic Assessment |
| |
| Lipase Increased | Investigations | CTCAE v 5.0 | Systematic Assessment |
| |
| Lung Infection | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| Lymphedema | Vascular disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | CTCAE v 5.0 | Systematic Assessment |
| |
| Malaise | General disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Mucositis oral | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Muscle Weakness Lower Limb | Musculoskeletal and connective tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Muscle Weakness Right-Sided | Nervous system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Musculoskeletal and connective tissue disorder - Other | Musculoskeletal and connective tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| myalgia | Musculoskeletal and connective tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Nail Changes | Skin and subcutaneous tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Neck Edema | General disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Neck Pain | Musculoskeletal and connective tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Nervous System Disorders- Other | Nervous system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Neutrophil Count Decreased | Investigations | CTCAE v 5.0 | Systematic Assessment |
| |
| Non-Cardiac Chest Pain | General disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Oral Dysesthesia | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Oral Pain | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Pain | General disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Pain in Extremity | Musculoskeletal and connective tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Paresthesia | Nervous system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Peripheral Motor Neuropathy | Nervous system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Peripheral Sensory Neuropathy | Nervous system disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Photophobia | Eye disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Platelet Count Decreased | Investigations | CTCAE v 5.0 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Rash Acneiform | Skin and subcutaneous tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Rash Maculo-Papular | Skin and subcutaneous tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Respiratory, thoracic and mediastinal disorders - Other, specify | Respiratory, thoracic and mediastinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| Sinus Bradycardia | Cardiac disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| Skin and subcutaneous tissue disorders - Other | Skin and subcutaneous tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Skin Hyperpigmentation | Skin and subcutaneous tissue disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Skin Infection | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| Small Intestinal Obstruction | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Sore Throat | Respiratory, thoracic and mediastinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Thromboembolic Event | Vascular disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Tooth Infection | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| Tumor pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE v 5.0 | Systematic Assessment |
| |
| Urine Discoloration | Renal and urinary disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Vaccination Site Lymphadenopathy | General disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Vaccination Complication | Injury, poisoning and procedural complications | CTCAE v 5.0 | Systematic Assessment |
| |
| Vaginal Infection | Infections and infestations | CTCAE v 5.0 | Systematic Assessment |
| |
| Vascular Access Complication | Injury, poisoning and procedural complications | CTCAE v 5.0 | Systematic Assessment |
| |
| Vascular Disorders- Other | Vascular disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Vasculitis | Vascular disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE v 5.0 | Systematic Assessment |
| |
| Weight Loss | Investigations | CTCAE v 5.0 | Systematic Assessment |
| |
| White Blood Cell Decreased | Investigations | CTCAE v 5.0 | Systematic Assessment |
|
Adequate paired biopsy specimens for Tumor and Stroma With Infiltrating Lymphocytes (TIL) and protein Programmed Death-Ligand 1 (PD-L1) analysis were not obtained for all of the enrolled and treated patients due to insufficient tissue amounts.
All study data and results will be owned by the institution. Subject to the terms and conditions of this agreement, institution and principal investigator have the right to publish or publicly present the results of the study. Merck shall have the right to review and comment on any public presentation. No public presentation shall contain any confidential information of Merck.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Massey CTO Breast Team | Virginia Commonwealth University Massey Cancer Center | 804-628-6430 | masseyctbrst@vcu.edu |
| Sep 14, 2023 |
| Prot_SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 12, 2022 | Jan 19, 2023 | ICF_000.pdf |
Not provided
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D064726 | Triple Negative Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D004317 | Doxorubicin |
| D003520 | Cyclophosphamide |
| D017239 | Paclitaxel |
| D000068196 | Albumin-Bound Paclitaxel |
| D016190 | Carboplatin |
| D000077209 | Decitabine |
| C582435 | pembrolizumab |
| ID | Term |
|---|---|
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D000418 | Albumins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D056831 | Coordination Complexes |
| D001374 | Azacitidine |
| D001372 | Aza Compounds |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| Absolute Change Value |
|
| OG001 | Cohort B: HER2-negative Hormone Receptor-positive Tumors | HER2-negative hormone receptor-positive tumors (Cohort B): Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
| OG002 | Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab | Triple Negative Breast Cancer (Cohort A2). Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin, and pembrolizumab every 3 weeks. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin AUC 1.5 once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
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| OG002 | Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab | Triple Negative Breast Cancer (Cohort A2). Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin, and pembrolizumab every 3 weeks. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin AUC 1.5 once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
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HER2-negative hormone receptor-positive tumors (Cohort B): Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
| OG002 | Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab | Triple Negative Breast Cancer (Cohort A2). Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin, and pembrolizumab every 3 weeks. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin AUC 1.5 once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
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| OG002 | Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab | Triple Negative Breast Cancer (Cohort A2). Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin, and pembrolizumab every 3 weeks. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin AUC 1.5 once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
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| OG002 | Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab | Triple Negative Breast Cancer (Cohort A2). Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin, and pembrolizumab every 3 weeks. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin IV 1.5 area under curve (AUC) once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
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HER2-negative hormone receptor-positive tumors (Cohort B): Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
| OG002 | Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab | Triple Negative Breast Cancer (Cohort A2). Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin, and pembrolizumab every 3 weeks. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin AUC 1.5 once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
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| OG001 | Cohort B: HER2-negative Hormone Receptor-positive Tumors | HER2-negative hormone receptor-positive tumors (Cohort B): Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
| OG002 | Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab | Triple Negative Breast Cancer (Cohort A2). Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin, and pembrolizumab every 3 weeks. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin IV 1.5 area under curve (AUC) once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
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Triple Negative Breast Cancer (Cohort A): Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin IV 1.5 area under curve (AUC) once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
| OG001 | Cohort B: HER2-negative Hormone Receptor-positive Tumors | HER2-negative hormone receptor-positive tumors (Cohort B): Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
| OG002 | Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab | Triple Negative Breast Cancer (Cohort A2). Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin, and pembrolizumab every 3 weeks. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin IV 1.5 area under curve (AUC) once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
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| OG002 | Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab | Triple Negative Breast Cancer (Cohort A2). Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin, and pembrolizumab every 3 weeks. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin AUC 1.5 once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
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| OG002 | Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab | Triple Negative Breast Cancer (Cohort A2). Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin, and pembrolizumab every 3 weeks. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin AUC 1.5 once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
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| OG002 | Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab | Triple Negative Breast Cancer (Cohort A2). Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin, and pembrolizumab every 3 weeks. Doxorubicin: 60 mg/m2 once every 2 weeks for 4 cycles. Cyclophosphamide: cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles. Paclitaxel: Paclitaxel 80 mg/m2 IV once weekly for 12 weeks. Carboplatin: carboplatin IV 1.5 area under curve (AUC) once weekly for 12 weeks. Decitabine: Given IV Pembrolizumab: Given IV |
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