Trial Outcomes & Findings for Neoadjuvant Pembrolizumab + Decitabine Followed by Std Neoadj Chemo for Locally Advanced HER2- Breast Ca (NCT NCT02957968)

Last Updated: 2026-04-21

Results Overview

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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

46 participants

Primary outcome timeframe

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

Results posted on

2026-04-21

Participant Flow

Participant milestones

Participant milestones
Measure	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	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	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
Overall Study STARTED	21	18	7
Overall Study COMPLETED	17	14	6
Overall Study NOT COMPLETED	4	4	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A: Triple Negative Breast Cancer (TNBC) n=21 Participants 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	Cohort B: HER2-negative Hormone Receptor-positive Tumors n=18 Participants 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	Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab n=7 Participants 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	Total n=46 Participants Total of all reporting groups
Age, Continuous	56 Years n=13 Participants	54 Years n=13 Participants	55 Years n=26 Participants	54.5 Years n=15 Participants
Sex: Female, Male Female	21 Participants n=13 Participants	18 Participants n=13 Participants	7 Participants n=26 Participants	46 Participants n=15 Participants
Sex: Female, Male Male	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants	0 Participants n=15 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=13 Participants	1 Participants n=13 Participants	0 Participants n=26 Participants	1 Participants n=15 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=13 Participants	17 Participants n=13 Participants	7 Participants n=26 Participants	45 Participants n=15 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants	0 Participants n=15 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants	0 Participants n=15 Participants
Race (NIH/OMB) Asian	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants	0 Participants n=15 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants	0 Participants n=15 Participants
Race (NIH/OMB) Black or African American	6 Participants n=13 Participants	6 Participants n=13 Participants	1 Participants n=26 Participants	13 Participants n=15 Participants
Race (NIH/OMB) White	15 Participants n=13 Participants	12 Participants n=13 Participants	6 Participants n=26 Participants	33 Participants n=15 Participants
Race (NIH/OMB) More than one race	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants	0 Participants n=15 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants	0 Participants n=15 Participants
Region of Enrollment United States	21 participants n=13 Participants	18 participants n=13 Participants	7 participants n=26 Participants	46 participants n=15 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Cohort A: Triple Negative Breast Cancer (TNBC) n=17 Participants 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	Cohort B: HER2-negative Hormone Receptor-positive Tumors n=14 Participants 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	Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab n=6 Participants 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
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. Baseline	27.35 % of stromal area occupied by TIL Standard Deviation 17.69	17.50 % of stromal area occupied by TIL Standard Deviation 9.95	25.83 % of stromal area occupied by TIL Standard Deviation 12.01
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. Post Treatment	35.00 % of stromal area occupied by TIL Standard Deviation 21.43	23.57 % of stromal area occupied by TIL Standard Deviation 12.00	32.50 % of stromal area occupied by TIL Standard Deviation 11.73
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. Absolute Change Value	7.65 % of stromal area occupied by TIL Standard Deviation 15.12	6.07 % of stromal area occupied by TIL Standard Deviation 8.13	6.67 % of stromal area occupied by TIL Standard Deviation 12.11

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Cohort A: Triple Negative Breast Cancer (TNBC) n=21 Participants 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	Cohort B: HER2-negative Hormone Receptor-positive Tumors n=18 Participants 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	Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab n=7 Participants 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
Number of Adverse Events (AEs) Reported During and After Immune Treatment (ie, Decitabine and Pembrolizumab)	215 Adverse Events Reported	151 Adverse Events Reported	98 Adverse Events Reported

SECONDARY outcome

Timeframe: Assessed at end of administration of decitabine and pembrolizumab Day- Window of time Days 25-29

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.)

Outcome measures

Outcome measures
Measure	Cohort A: Triple Negative Breast Cancer (TNBC) n=17 Participants 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	Cohort B: HER2-negative Hormone Receptor-positive Tumors n=14 Participants 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	Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab n=6 Participants 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
Number of Patients Meeting Criteria for Lymphocyte-predominant Breast Cancer (LPBC) Following Treatment With Decitabine and Pembrolizumab	3 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: End of administration of decitabine and pembrolizumab Day- Window of time Days 25-29, or 30 days following surgery

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Cohort A: Triple Negative Breast Cancer (TNBC) n=20 Participants 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	Cohort B: HER2-negative Hormone Receptor-positive Tumors n=16 Participants 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	Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab n=7 Participants 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
Number of Patients With Pathologic Complete Response (pCR) in the Breast and Post-therapy Lymph Nodes.	10 Participants	3 Participants	1 Participants

SECONDARY outcome

Timeframe: End of therapy surgery

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Cohort A: Triple Negative Breast Cancer (TNBC) n=13 Participants 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	Cohort B: HER2-negative Hormone Receptor-positive Tumors n=5 Participants 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	Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab n=2 Participants 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
Number of Patients With no or Minimal Residual Disease in the Resected Breast and Axillary Specimen. 0 (no MRD)	10 Participants	3 Participants	1 Participants
Number of Patients With no or Minimal Residual Disease in the Resected Breast and Axillary Specimen. i (MRD present)	3 Participants	2 Participants	1 Participants

SECONDARY outcome

Timeframe: End of therapy surgery

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.

Outcome measures

Outcome measures
Measure	Cohort A: Triple Negative Breast Cancer (TNBC) n=20 Participants 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	Cohort B: HER2-negative Hormone Receptor-positive Tumors n=16 Participants 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	Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab n=7 Participants 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
The Number of Patients With Clinical Complete Response (cCR) cCR=No	6 Participants	8 Participants	5 Participants
The Number of Patients With Clinical Complete Response (cCR) cCR=Yes	14 Participants	8 Participants	2 Participants

SECONDARY outcome

Timeframe: Assessed at end of administration of decitabine and pembrolizumab Day- Window of time Days 25-29

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Assessed at end of administration of decitabine and pembrolizumab Day- Window of time Days 25-29

Population: 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

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.

Outcome measures

Outcome measures
Measure	Cohort A: Triple Negative Breast Cancer (TNBC) n=17 Participants 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	Cohort B: HER2-negative Hormone Receptor-positive Tumors n=14 Participants 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	Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab n=6 Participants 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
Evaluation of Expression of Protein Programmed Death-Ligand 1 (PD-L1) Within Tumor, Stroma, and Infiltrating Immune Cells Combined, at Baseline and Following Immunotherapy. Baseline (Bx 1)	31.00 Number of PD-L1 positive cells Standard Deviation 29.63	13.07 Number of PD-L1 positive cells Standard Deviation 17.22	22.50 Number of PD-L1 positive cells Standard Deviation 23.36
Evaluation of Expression of Protein Programmed Death-Ligand 1 (PD-L1) Within Tumor, Stroma, and Infiltrating Immune Cells Combined, at Baseline and Following Immunotherapy. Post Immunotherapy	50.00 Number of PD-L1 positive cells Standard Deviation 34.73	29.07 Number of PD-L1 positive cells Standard Deviation 28.15	35.50 Number of PD-L1 positive cells Standard Deviation 26.04
Evaluation of Expression of Protein Programmed Death-Ligand 1 (PD-L1) Within Tumor, Stroma, and Infiltrating Immune Cells Combined, at Baseline and Following Immunotherapy. Change (Bx2-Bx1)	19.00 Number of PD-L1 positive cells Standard Deviation 24.27	16.00 Number of PD-L1 positive cells Standard Deviation 28.15	13.00 Number of PD-L1 positive cells Standard Deviation 17.12

SECONDARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Cohort A: Triple Negative Breast Cancer (TNBC) n=32 Tumor Biopsies 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	Cohort B: HER2-negative Hormone Receptor-positive Tumors n=26 Tumor Biopsies 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	Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab n=12 Tumor Biopsies 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
Change of Intensity of Programmed Death-Ligand 1 (PD-L1) Expression by Assay as it Relates to Pathologic Complete Response (pCR) Rates From Chemotherapy BX2 (only) CPS After Therapy	0.1211 Corr. Coefficient pCR & PD-L1 CPS Interval -0.3986 to 0.5818	0.0031 Corr. Coefficient pCR & PD-L1 CPS Interval -0.5489 to 0.5531	-0.0094 Corr. Coefficient pCR & PD-L1 CPS Interval -0.8147 to 0.8084
Change of Intensity of Programmed Death-Ligand 1 (PD-L1) Expression by Assay as it Relates to Pathologic Complete Response (pCR) Rates From Chemotherapy Change CPS of BX2-BX1	0.44541 Corr. Coefficient pCR & PD-L1 CPS Interval -0.0645 to 0.7709	-0.4719 Corr. Coefficient pCR & PD-L1 CPS Interval -0.8118 to 0.1068	-0.8011 Corr. Coefficient pCR & PD-L1 CPS Interval -0.9773 to 0.0299

SECONDARY outcome

Timeframe: Baseline biopsy (BX1) prior to therapy, EOT surgery 2nd core biopsy (BX2) 3-7 days following last dose of pre-chemotherapy pembrolizumab

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Cohort A: Triple Negative Breast Cancer (TNBC) n=34 Tumor Biopsies 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	Cohort B: HER2-negative Hormone Receptor-positive Tumors n=28 Tumor Biopsies 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	Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab n=12 Tumor Biopsies 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
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. BX2 (only) Hscore (After therapy)	0.25211 Corr. Coefficient pCR & PD-L1 H-Score Interval -0.2601 to 0.6535	0.7121 Corr. Coefficient pCR & PD-L1 H-Score Interval 0.2917 to 0.9019	-0.3647 Corr. Coefficient pCR & PD-L1 H-Score Interval -0.9076 to 0.6348
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. Change_Hscore of Bx-2-Bx-1	0.3699 Corr. Coefficient pCR & PD-L1 H-Score Interval -0.1347 to 0.7221	-0.1407 Corr. Coefficient pCR & PD-L1 H-Score Interval -0.6246 to 0.4213	-0.8592 Corr. Coefficient pCR & PD-L1 H-Score Interval -0.9844 to -0.15734

SECONDARY outcome

Timeframe: Assessed at end of administration of decitabine compared to assessment at baseline prior to protocol treatments.

Evaluate the level of circulating MDSC per ml of blood at baseline, following treatment with decitabine alone.

Outcome measures

Outcome measures
Measure	Cohort A: Triple Negative Breast Cancer (TNBC) n=20 Participants 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	Cohort B: HER2-negative Hormone Receptor-positive Tumors n=18 Participants 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	Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab n=7 Participants 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
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-decitabine Compared to MDSC Found in Blood Samples Collected at Baseline. Baseline Granulocytic	13271.20 absolute cell count per ml of blood Standard Deviation 24742.36	22575.50 absolute cell count per ml of blood Standard Deviation 34814.99	77038.71 absolute cell count per ml of blood Standard Deviation 127561.51
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-decitabine Compared to MDSC Found in Blood Samples Collected at Baseline. Post Decitabine- Granulocytic	6279.00 absolute cell count per ml of blood Standard Deviation 8391.41	38759.50 absolute cell count per ml of blood Standard Deviation 67973.42	43120.00 absolute cell count per ml of blood Standard Deviation 60999.23
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-decitabine Compared to MDSC Found in Blood Samples Collected at Baseline. Change- Granulocytic	-6992.20 absolute cell count per ml of blood Standard Deviation 27388.05	16184.00 absolute cell count per ml of blood Standard Deviation 46253.09	-33918.71 absolute cell count per ml of blood Standard Deviation 107087.59
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-decitabine Compared to MDSC Found in Blood Samples Collected at Baseline. Baseline- Monocytic	59222.05 absolute cell count per ml of blood Standard Deviation 85757.80	45450.33 absolute cell count per ml of blood Standard Deviation 46641.67	15843.29 absolute cell count per ml of blood Standard Deviation 10160.61
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-decitabine Compared to MDSC Found in Blood Samples Collected at Baseline. Post Decitabine- Monocytic	20524.50 absolute cell count per ml of blood Standard Deviation 16081.57	18886.00 absolute cell count per ml of blood Standard Deviation 18101.69	16081.57 absolute cell count per ml of blood Standard Deviation 13631.21
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-decitabine Compared to MDSC Found in Blood Samples Collected at Baseline. Change	-38697.55 absolute cell count per ml of blood Standard Deviation 77519.71	-26564.33 absolute cell count per ml of blood Standard Deviation 35958.06	238.29 absolute cell count per ml of blood Standard Deviation 10580.07
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-decitabine Compared to MDSC Found in Blood Samples Collected at Baseline. Baseline- Total-MDSC	83927.60 absolute cell count per ml of blood Standard Deviation 96291.84	213321.11 absolute cell count per ml of blood Standard Deviation 579434.80	138957.43 absolute cell count per ml of blood Standard Deviation 222790.89
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-decitabine Compared to MDSC Found in Blood Samples Collected at Baseline. Post Decitabine- Total MDSC	35606.00 absolute cell count per ml of blood Standard Deviation 26267.93	146345.39 absolute cell count per ml of blood Standard Deviation 310850.15	92662.71 absolute cell count per ml of blood Standard Deviation 100386.82
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-decitabine Compared to MDSC Found in Blood Samples Collected at Baseline. Change- Total MDSC	-48321.60 absolute cell count per ml of blood Standard Deviation 89365.64	-66975.72 absolute cell count per ml of blood Standard Deviation 283701.53	-46294.71 absolute cell count per ml of blood Standard Deviation 146651.36

SECONDARY outcome

Timeframe: Assessed at baseline, after administration of decitabine, after decitabine and 2 doses of pembrolizumab.

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.

Outcome measures

Outcome measures
Measure	Cohort A: Triple Negative Breast Cancer (TNBC) n=20 Participants 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	Cohort B: HER2-negative Hormone Receptor-positive Tumors n=18 Participants 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	Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab n=7 Participants 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
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-pembrolizumab Compared to MDSC Found in Blood Samples Collected at Baseline. Baseline- Granulocytic	13271.20 Absolute cell count per ml of blood Standard Deviation 24742.36	22575.50 Absolute cell count per ml of blood Standard Deviation 34814.99	77038.71 Absolute cell count per ml of blood Standard Deviation 127561.51
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-pembrolizumab Compared to MDSC Found in Blood Samples Collected at Baseline. Post Pembrolizumab- Granulocytic	33099.40 Absolute cell count per ml of blood Standard Deviation 83017.97	25780.33 Absolute cell count per ml of blood Standard Deviation 34038.45	63045.29 Absolute cell count per ml of blood Standard Deviation 87400.02
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-pembrolizumab Compared to MDSC Found in Blood Samples Collected at Baseline. Change(Post Pembro-Baseline) Granulocytic	19828.20 Absolute cell count per ml of blood Standard Deviation 81974.04	3204.83 Absolute cell count per ml of blood Standard Deviation 38451.35	-13993.43 Absolute cell count per ml of blood Standard Deviation 136887.63
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-pembrolizumab Compared to MDSC Found in Blood Samples Collected at Baseline. Baseline- Monocytic	59222.05 Absolute cell count per ml of blood Standard Deviation 85757.80	45450.33 Absolute cell count per ml of blood Standard Deviation 46641.67	15843.29 Absolute cell count per ml of blood Standard Deviation 10160.61
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-pembrolizumab Compared to MDSC Found in Blood Samples Collected at Baseline. Post Pembrolizumab- Monocytic	22499.95 Absolute cell count per ml of blood Standard Deviation 23347.79	21651.56 Absolute cell count per ml of blood Standard Deviation 38761.10	18028.43 Absolute cell count per ml of blood Standard Deviation 20787.90
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-pembrolizumab Compared to MDSC Found in Blood Samples Collected at Baseline. Change (Post Pembro- Baseline)- Monocytic	-36722.10 Absolute cell count per ml of blood Standard Deviation 72130.68	-23798.78 Absolute cell count per ml of blood Standard Deviation 53965.00	2185.14 Absolute cell count per ml of blood Standard Deviation 21374.82
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-pembrolizumab Compared to MDSC Found in Blood Samples Collected at Baseline. Baseline- Total MDSC	83927.60 Absolute cell count per ml of blood Standard Deviation 96291.84	213321.11 Absolute cell count per ml of blood Standard Deviation 579434.80	138957.43 Absolute cell count per ml of blood Standard Deviation 222790.89
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-pembrolizumab Compared to MDSC Found in Blood Samples Collected at Baseline. Post Pembrolizumab- Total MDSC	74569.75 Absolute cell count per ml of blood Standard Deviation 119875.91	78836.72 Absolute cell count per ml of blood Standard Deviation 89861.88	133082.00 Absolute cell count per ml of blood Standard Deviation 91911.07
Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-pembrolizumab Compared to MDSC Found in Blood Samples Collected at Baseline. Change (Post Pembro-Baseline)- Total MDSC	-9357.85 Absolute cell count per ml of blood Standard Deviation 82232.70	-134484.39 Absolute cell count per ml of blood Standard Deviation 595746.30	-5875.43 Absolute cell count per ml of blood Standard Deviation 203496.45

SECONDARY outcome

Timeframe: 12 Months following surgery

Population: Patients who did not have surgery due to disease progression or experienced disease progression before undergoing surgery were excluded.

Number of patients who are alive and have not had disease relapse at 12 months following last dose of pembrolizumab

Outcome measures

Outcome measures
Measure	Cohort A: Triple Negative Breast Cancer (TNBC) n=18 Participants 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	Cohort B: HER2-negative Hormone Receptor-positive Tumors n=16 Participants 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	Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab n=6 Participants 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
Event Free Survival (EFS) Rate at 12 Months Following the Last Dose of Pembrolizumab. Had Progression at 12-month after Surgery	2 Participants	0 Participants	0 Participants
Event Free Survival (EFS) Rate at 12 Months Following the Last Dose of Pembrolizumab. No Progression at 12-month after Surgery	16 Participants	16 Participants	6 Participants

Adverse Events

Cohort B: HER2-negative Hormone Receptor-positive Tumors

Serious events: 6 serious events

Other events: 18 other events

Deaths: 0 deaths

Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

Cohort A: Triple Negative Breast Cancer (TNBC)

Serious events: 7 serious events

Other events: 21 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Massey CTO Breast Team

Virginia Commonwealth University Massey Cancer Center

Phone: 804-628-6430

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER