ClinicalTrials.gov

History of Changes for Study: NCT03725059
Study of Pembrolizumab (MK-3475) Versus Placebo in Combination With Neoadjuvant Chemotherapy & Adjuvant Endocrine Therapy in the Treatment of Early-Stage Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (MK-3475-756/KEYNOTE-756)
Latest version (submitted July 27, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 October 29, 2018 None (earliest Version on record)
2 December 19, 2018 Recruitment Status, Study Status, Contacts/Locations and IPDSharing
3 January 3, 2019 Study Status and Contacts/Locations
4 January 10, 2019 Contacts/Locations and Study Status
5 January 18, 2019 Contacts/Locations and Study Status
6 January 25, 2019 Contacts/Locations and Study Status
7 January 31, 2019 Contacts/Locations and Study Status
8 February 8, 2019 Study Status and Contacts/Locations
9 February 14, 2019 Contacts/Locations, Study Status and Study Identification
10 February 22, 2019 Contacts/Locations and Study Status
11 February 28, 2019 Contacts/Locations and Study Status
12 March 8, 2019 Study Status and Contacts/Locations
13 March 14, 2019 Contacts/Locations and Study Status
14 March 22, 2019 Contacts/Locations and Study Status
15 March 26, 2019 Contacts/Locations and Study Status
16 April 4, 2019 Study Status and Contacts/Locations
17 April 11, 2019 Contacts/Locations and Study Status
18 April 17, 2019 Contacts/Locations and Study Status
19 April 26, 2019 Contacts/Locations and Study Status
20 May 3, 2019 Contacts/Locations and Study Status
21 May 9, 2019 Contacts/Locations and Study Status
22 May 17, 2019 Contacts/Locations and Study Status
23 May 22, 2019 Contacts/Locations and Study Status
24 May 30, 2019 Contacts/Locations and Study Status
25 June 7, 2019 Study Status and Contacts/Locations
26 June 11, 2019 Contacts/Locations and Study Status
27 June 20, 2019 Study Identification, Contacts/Locations, Eligibility, Outcome Measures and Study Status
28 June 25, 2019 Contacts/Locations and Study Status
29 July 4, 2019 Study Status and Contacts/Locations
30 July 11, 2019 Contacts/Locations and Study Status
31 July 18, 2019 Contacts/Locations and Study Status
32 July 24, 2019 Contacts/Locations and Study Status
33 August 8, 2019 Study Status
34 August 21, 2019 Contacts/Locations and Study Status
35 August 28, 2019 Contacts/Locations and Study Status
36 September 4, 2019 Contacts/Locations and Study Status
37 September 13, 2019 Contacts/Locations and Study Status
38 September 27, 2019 Contacts/Locations and Study Status
39 October 10, 2019 Study Status and Contacts/Locations
40 October 18, 2019 Contacts/Locations and Study Status
41 October 25, 2019 Contacts/Locations and Study Status
42 November 7, 2019 Contacts/Locations and Study Status
43 November 13, 2019 Contacts/Locations and Study Status
44 November 22, 2019 Contacts/Locations and Study Status
45 December 5, 2019 Study Status and Contacts/Locations
46 December 12, 2019 Contacts/Locations and Study Status
47 December 22, 2019 Contacts/Locations, References and Study Status
48 December 27, 2019 Contacts/Locations and Study Status
49 January 14, 2020 Outcome Measures, Arms and Interventions and Study Status
50 January 27, 2020 Contacts/Locations and Study Status
51 February 14, 2020 Contacts/Locations and Study Status
52 February 21, 2020 Contacts/Locations and Study Status
53 February 25, 2020 Contacts/Locations and Study Status
54 March 6, 2020 Contacts/Locations and Study Status
55 March 12, 2020 Contacts/Locations and Study Status
56 March 20, 2020 Contacts/Locations and Study Status
57 March 27, 2020 Contacts/Locations and Study Status
58 April 2, 2020 Study Status
59 April 17, 2020 Contacts/Locations and Study Status
60 April 23, 2020 Contacts/Locations and Study Status
61 April 29, 2020 Contacts/Locations and Study Status
62 May 7, 2020 Study Status and Contacts/Locations
63 May 15, 2020 Contacts/Locations and Study Status
64 May 28, 2020 Contacts/Locations and Study Status
65 June 18, 2020 Study Status and Contacts/Locations
66 June 25, 2020 Contacts/Locations and Study Status
67 July 10, 2020 Contacts/Locations and Study Status
68 July 16, 2020 Contacts/Locations and Study Status
69 July 22, 2020 Contacts/Locations and Study Status
70 July 29, 2020 Contacts/Locations and Study Status
71 August 7, 2020 Contacts/Locations and Study Status
72 August 12, 2020 Contacts/Locations and Study Status
73 August 27, 2020 Contacts/Locations and Study Status
74 September 4, 2020 Contacts/Locations and Study Status
75 September 10, 2020 Contacts/Locations and Study Status
76 September 18, 2020 Contacts/Locations and Study Status
77 September 23, 2020 Contacts/Locations and Study Status
78 October 1, 2020 Contacts/Locations and Study Status
79 October 8, 2020 Study Status and Contacts/Locations
80 October 16, 2020 Contacts/Locations and Study Status
81 October 23, 2020 Contacts/Locations and Study Status
82 October 28, 2020 Contacts/Locations and Study Status
83 November 5, 2020 Study Status and Contacts/Locations
84 November 12, 2020 Contacts/Locations and Study Status
85 November 19, 2020 Contacts/Locations and Study Status
86 November 25, 2020 Contacts/Locations and Study Status
87 December 2, 2020 Contacts/Locations and Study Status
88 December 9, 2020 Contacts/Locations and Study Status
89 December 17, 2020 Contacts/Locations and Study Status
90 December 23, 2020 Contacts/Locations and Study Status
91 January 7, 2021 Contacts/Locations and Study Status
92 January 13, 2021 Contacts/Locations and Study Status
93 January 21, 2021 Contacts/Locations and Study Status
94 January 29, 2021 Contacts/Locations and Study Status
95 February 12, 2021 Contacts/Locations and Study Status
96 February 19, 2021 Contacts/Locations and Study Status
97 February 26, 2021 Contacts/Locations and Study Status
98 March 4, 2021 Contacts/Locations and Study Status
99 March 11, 2021 Contacts/Locations and Study Status
100 March 25, 2021 Contacts/Locations and Study Status
101 April 1, 2021 Contacts/Locations and Study Status
102 April 9, 2021 Contacts/Locations and Study Status
103 April 17, 2021 Contacts/Locations and Study Status
104 April 22, 2021 Contacts/Locations and Study Status
105 May 6, 2021 Contacts/Locations, Outcome Measures, Arms and Interventions, Study Status and Eligibility
106 May 13, 2021 Contacts/Locations and Study Status
107 May 21, 2021 Contacts/Locations and Study Status
108 May 28, 2021 Contacts/Locations and Study Status
109 June 4, 2021 Contacts/Locations and Study Status
110 June 18, 2021 Contacts/Locations and Study Status
111 June 24, 2021 Contacts/Locations and Study Status
112 July 22, 2021 Contacts/Locations and Study Status
113 July 29, 2021 Contacts/Locations and Study Status
114 August 5, 2021 Contacts/Locations and Study Status
115 August 20, 2021 Contacts/Locations and Study Status
116 August 27, 2021 Contacts/Locations and Study Status
117 September 3, 2021 Contacts/Locations and Study Status
118 September 9, 2021 Contacts/Locations and Study Status
119 September 15, 2021 Contacts/Locations and Study Status
120 September 23, 2021 Contacts/Locations and Study Status
121 September 30, 2021 Contacts/Locations and Study Status
122 October 8, 2021 Contacts/Locations and Study Status
123 October 21, 2021 Contacts/Locations and Study Status
124 October 27, 2021 Contacts/Locations and Study Status
125 November 3, 2021 Contacts/Locations and Study Status
126 November 10, 2021 Contacts/Locations and Study Status
127 November 24, 2021 Contacts/Locations and Study Status
128 December 3, 2021 Contacts/Locations and Study Status
129 December 9, 2021 Contacts/Locations and Study Status
130 December 17, 2021 Contacts/Locations and Study Status
131 December 23, 2021 Contacts/Locations and Study Status
132 January 10, 2022 Contacts/Locations, Outcome Measures, Arms and Interventions, Study Status and Study Design
133 February 4, 2022 Contacts/Locations and Study Status
134 February 10, 2022 Contacts/Locations and Study Status
135 February 18, 2022 Contacts/Locations and Study Status
136 February 25, 2022 Contacts/Locations and Study Status
137 March 4, 2022 Contacts/Locations and Study Status
138 March 11, 2022 Contacts/Locations and Study Status
139 March 17, 2022 Contacts/Locations and Study Status
140 March 24, 2022 Contacts/Locations and Study Status
141 March 31, 2022 Contacts/Locations and Study Status
142 April 13, 2022 Contacts/Locations and Study Status
143 April 21, 2022 Contacts/Locations and Study Status
144 April 29, 2022 Contacts/Locations and Study Status
145 May 13, 2022 Contacts/Locations and Study Status
146 June 9, 2022 Contacts/Locations and Study Status
147 June 23, 2022 Contacts/Locations and Study Status
148 July 14, 2022 Contacts/Locations and Study Status
149 July 20, 2022 Contacts/Locations and Study Status
150 July 27, 2022 Recruitment Status, Contacts/Locations and Study Status
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Study NCT03725059
Submitted Date:  October 29, 2018 (v1)

Open or close this module Study Identification
Unique Protocol ID: 3475-756
Brief Title: Study of Pembrolizumab (MK-3475) Versus Placebo in Combination With Neoadjuvant Chemotherapy & Adjuvant Endocrine Therapy in the Treatment of Early-Stage Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (MK-3475-756/KEYNOTE-756)
Official Title: A Randomized, Double-Blind, Phase III Study of Pembrolizumab Versus Placebo in Combination With Neoadjuvant Chemotherapy and Adjuvant Endocrine Therapy for the Treatment of High-Risk Early-Stage Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (KEYNOTE-756)
Secondary IDs: 2017-004869-27 [EudraCT Number]
MK-3475-756 [Merck Protocol Number]
Open or close this module Study Status
Record Verification: October 2018
Overall Status: Not yet recruiting
Study Start: December 27, 2018
Primary Completion: January 24, 2031 [Anticipated]
Study Completion: January 24, 2031 [Anticipated]
First Submitted: October 29, 2018
First Submitted that
Met QC Criteria:
October 29, 2018
First Posted: October 30, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
October 29, 2018
Last Update Posted: October 30, 2018 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Merck Sharp & Dohme LLC
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary:

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) versus placebo in combination with neoadjuvant (pre-surgery) chemotherapy and adjuvant (post-surgery) endocrine therapy in the treatment of adults who have high-risk early-stage estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer.

The primary study hypotheses are: 1) pembrolizumab is superior to placebo, both in combination with the protocol-specified neoadjuvant anticancer therapy, as assessed by pathological Complete Response (pCR) rate defined by the local pathologist, and 2) pembrolizumab is superior to placebo (both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies) as assessed by Event-Free Survival (EFS) as determined by the investigator. The study is considered to have met its primary objective if pembrolizumab is superior to placebo with respect to either pCR (ypT0/Tis ypN0) or EFS.

Detailed Description: Study participants will receive 8 cycles of neoadjuvant study treatment and then will undergo surgery for their breast cancer. After surgery, participants will receive 9 cycles of study treatment and up to 10 years of variable endocrine therapy. Each cycle is 21 days long.
Open or close this module Conditions
Conditions: Breast Cancer
Keywords: PD1
PD-1
PDL1
PD-L1
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 1140 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Pembrolizumab+Chemotherapy (KX/KA[E]C)
In the neoadjuvant setting, participants receive pembrolizumab (K) 200 mg via intravenous (IV) infusion once every 3 weeks (Q3W) + paclitaxel (X) 80 mg/m^2 via IV infusion once weekly (QW) for 4 cycles (Treatment 1), followed by pembrolizumab 200 mg via IV infusion + doxorubicin or epirubicin (A or E; 60 mg/m^2 or 100 mg/m^2) via IV infusion Q3W + cyclophosphamide (C) 600 mg/m^2 via IV infusion Q3W for 4 cycles (Treatment 2). At 3 to 6 weeks after last cycle of neoadjuvant treatment, participants will undergo definitive surgery for their breast cancer. After surgery, participants will begin adjuvant study treatment. In the adjuvant setting, participants receive pembrolizumab 200 mg via IV infusion Q3W for 9 cycles + variable endocrine therapy for up to 10 years. Each cycle is 21 days long.
Biological: Pembrolizumab (K)
IV infusion Q3W
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Paclitaxel (X)
IV infusion QW
Other Names:
  • TAXOL®
Drug: Doxorubicin hydrochloride (A)
IV infusion Q3W
Other Names:
  • ADRIAMYCIN®
Drug: Epirubicin (E)
IV infusion Q3W
Other Names:
  • ELLENCE®
Drug: Cyclophosphamide (C)
IV infusion Q3W
Other Names:
  • CYTOXAN®
Drug: Endocrine therapy
Variable endocrine therapy for up 10 years
Radiation: Radiation therapy
Variable radiation therapy per local standard of care
Procedure: Surgery
Definitive surgery for breast cancer
Placebo Comparator: Placebo+Chemotherapy (PX/PA[E]C)
In the neoadjuvant setting, participants receive placebo (P; normal saline or dextrose) via IV infusion Q3W + paclitaxel (X) 80 mg/m^2 via IV infusion once weekly (QW) for 4 cycles (Treatment 1), followed by placebo via IV infusion + doxorubicin or epirubicin (A or E; 60 mg/m^2 or 100 mg/m^2) via IV infusion Q3W + cyclophosphamide (C) 600 mg/m^2 via IV infusion Q3W for 4 cycles (Treatment 2). At 3 to 6 weeks after last cycle of neoadjuvant treatment, participants will undergo definitive surgery for their breast cancer. After surgery, participants will begin adjuvant study treatment. In the adjuvant setting, participants receive placebo via IV infusion Q3W for 9 cycles + variable endocrine therapy for up to 10 years. Each cycle is 21 days long.
Drug: Placebo (P)
Normal saline or dextrose IV infusion Q3W
Drug: Paclitaxel (X)
IV infusion QW
Other Names:
  • TAXOL®
Drug: Doxorubicin hydrochloride (A)
IV infusion Q3W
Other Names:
  • ADRIAMYCIN®
Drug: Epirubicin (E)
IV infusion Q3W
Other Names:
  • ELLENCE®
Drug: Cyclophosphamide (C)
IV infusion Q3W
Other Names:
  • CYTOXAN®
Radiation: Radiation therapy
Variable radiation therapy per local standard of care
Procedure: Surgery
Definitive surgery for breast cancer
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0
[ Time Frame: Up to approximately 7 months (Time of surgery) ]

The pCR rate (ypT0/Tis ypN0) is defined as the percentage of participants without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by American Joint Committee on Cancer (AJCC) staging criteria (7th edition) assessed by the local pathologist at the time of definitive surgery. The percentage of participants with a pathological Complete Response (pCR) using the definition of (ypT0/Tis ypN0) will be presented for pembrolizumab versus placebo, both in combination with the protocol-specified neoadjuvant anticancer therapies.
2. Event-Free Survival (EFS)
[ Time Frame: Up to approximately 10 years ]

EFS is defined as the time from randomization to disease progression that: precludes definitive surgery, results in a local or distant recurrence, results in a second primary malignancy, or death due to any cause whichever occurs first. The EFS following administration of pembrolizumab and placebo, both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies, as determined by the investigator will be presented.
Secondary Outcome Measures:
1. Overall Survival (OS)
[ Time Frame: Up to approximately 10 years ]

OS is defined as the time from date of randomization to date of death due to any cause. The OS following administration of pembrolizumab and placebo, both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies will be presented.
2. pCR Rate Using the Definition of ypT0ypN0
[ Time Frame: Up to approximately 7 months (Time of surgery) ]

pCR rate (ypT0ypN0) is defined as the percentage of participants without residual invasive or in situ cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes after completion of neoadjuvant systemic therapy by AJCC staging criteria (7th edition) assessed by the local pathologist at the time of definitive surgery. The percentage of participants with a pCR using the definition of (ypT0ypN0) will be presented for pembrolizumab versus placebo, both in combination with the protocol-specified neoadjuvant anticancer therapies.
3. pCR Rate Using the Definition of ypT0/Tis
[ Time Frame: Up to approximately 7 months (Time of surgery) ]

pCR rate (ypT0/Tis) is defined as the percentage of participants without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen (independent of lymph node involvement) after completion of neoadjuvant systemic therapy by AJCC staging criteria (7th edition) assessed by the local pathologist at the time of definitive surgery. The percentage of participants with a pCR using the definition of ypT0/Tis will be presented for pembrolizumab versus placebo, both in combination with the protocol-specified neoadjuvant anticancer therapies.
4. pCR Rate Using the Definitions of ypT0/Tis ypN0, ypT0/Tis, and ypT0 ypN0 in Participants With a Combined Positive Score [CPS] ≥1
[ Time Frame: Up to approximately 7 months (Time of surgery) ]

pCR rates were calculated using the definitions of ypT0/Tis ypN0, ypT0/Tis, and ypT0 ypN0 after completion of neoadjuvant systemic therapy by AJCC staging criteria (7th edition) assessed by the local pathologist at the time of definitive surgery. The percentage of participants with a pCR using the three definitions of ypT0/Tis ypN0, ypT0/Tis, and ypT0 ypN0 in participants with a CPS ≥1 (with a positive Programmed Cell Death-Ligand 1 [PD-L1] tumor status) will be presented for pembrolizumab versus placebo, both in combination with the protocol-specified neoadjuvant anticancer therapies.
5. EFS in Participants With a CPS ≥1
[ Time Frame: Up to approximately 10 years ]

EFS is defined as the time from randomization to disease progression that: precludes definitive surgery, results in a local or distant recurrence, results in a second primary malignancy, or death due to any cause whichever occurs first. The EFS following administration of pembrolizumab and placebo, both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies, as determined by the investigator for participants with a CPS ≥1 will be presented.
6. OS in Participants With a CPS ≥1
[ Time Frame: Up to approximately 10 years ]

OS is defined as the time from date of randomization to date of death due to any cause. The OS following administration of pembrolizumab and placebo, both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies for participants with a CPS ≥1 will be presented.
7. Number of Participants Experiencing an Adverse Event (AE)
[ Time Frame: Up to approximately 15 months ]

An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE while receiving pembrolizumab or placebo (including 1 month of safety follow up) will be presented.
8. Number of Participants Experiencing a Serious Adverse Event (SAE)
[ Time Frame: Up to approximately 17 months ]

An SAE is defined as any untoward medical occurrence that, at any dose: Results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity or Is a congenital anomaly/birth defect. The number of participants who experience an SAE while receiving pembrolizumab or placebo (including 3 months of safety follow up) will be presented.
9. Number of Participants Experiencing an Immune-related AE (irAE)
[ Time Frame: Up to approximately 15 months ]

Some AEs that may occur in this study that are known to be related to pembrolizumab immunotherapy treatment and may include: pneumonitis, diarrhea/colitis, aspartate aminotransferase/alanine aminotransferase (AST/ALT) elevation or increased bilirubin, Type 1 diabetes mellitus or hyperglycemia, hypophysitis, hyperthyroidism, hypothyroidism, nephritis and renal dysfunction, and myocarditis. The number of participants who experience an irAE while receiving pembrolizumab or placebo (including 1 month of safety follow up) will be presented.
10. Number of Study Treatment Discontinuation Due to AEs
[ Time Frame: Up to approximately 14 months ]

The number of participants who discontinue study treatment (pembrolizumab or placebo) due to an AE will be presented.
11. Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire Core 30 (QLQ-C30) Score
[ Time Frame: Baseline (Cycle 1 Day 1 in Treatment 1) and Cycles 1 and 4 Day 1 in Treatment 2 (Up to approximately 5 months) Each cycle is 21 days. ]

The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Individual responses for each of 28 items are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome, and responses for each of 2 items (overall health and overall quality of life) are given on a 7-point scale (1=Very poor to 7=Excellent), with a higher score indicating a better outcome. The change from Baseline to end of treatment (up to Cycle 4 Day 1) in EORTC-QLQ-C30 scores for participants will be presented.
12. Change from Baseline in EORTC Breast Cancer-Specific QoL Questionnaire (QLQ-BR23) Score
[ Time Frame: Baseline (Cycle 1 Day 1 in Treatment 1) and Cycles 1 and 4 Day 1 in Treatment 2 (Up to approximately 5 months) Each cycle is 21 days. ]

The EORTC QLQ-BR23 is a 23-item questionnaire developed to assess the quality of life in women with breast cancer. Responses for each item are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome. The change from Baseline to end of treatment (up to Cycle 4 Day 1) in EORTC QLQ-BR23 score for participants will be presented.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Has a localized invasive breast ductal adenocarcinoma, confirmed by the local pathologist, that includes either T1c-T2 (tumor size ≥2 cm), clinical node stage (cN)1-cN2, or T3-T4, cN0-cN2. Note: Inflammatory breast cancer is allowed.
  • Has centrally confirmed ER+/HER2-, Grade 3 breast cancer of ductal histology, according to the most recent American Society of Clinical Oncology/College of American Pathologist guidelines.
  • Provides a new or recently obtained core needle biopsy, consisting of multiple cores, taken from the primary breast tumor(s) for central determination of HR status (ER and progesterone receptor), HER2, and PD-L1 status.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 10 days prior to initiation of study treatment.
  • Male participants must agree to use contraception during the treatment period and for at least 12 months (for participants who received cyclophosphamide) or 6 months (for participants who did not receive cyclophosphamide) after the last dose of study treatment and refrain from donating sperm during this period.
  • Female participants must agree to use effective contraception during the treatment period and for at least 12 months (for participants who received cyclophosphamide) or 6 months (for participants who did not receive cyclophosphamide) after the last dose of study treatment with pembrolizumab or placebo.
  • Has adequate organ function.

Exclusion Criteria:

  • Has a history of non-infectious pneumonitis that required treatment with steroids or has current pneumonitis.
  • Has breast cancer with lobular histology.
  • Has bilateral invasive breast cancer.
  • Has metastatic (Stage IV) breast cancer.
  • Has multi-centric breast cancer (presence of more than 1 tumor in different quadrants of the breast).
  • Has any of the following clinical lymph node staging per current American Joint Committee on Cancer (AJCC) staging criteria for breast cancer staging based on radiological and/or clinical assessment: cN3, cN3a, cN3b, or cN3c.
  • Has ER-, progesterone receptor positive breast cancer.
  • Has undergone excisional biopsy of the primary tumor and/or axillary lymph nodes or has undergone sentinel lymph node biopsy prior to study treatment.
  • Has a known additional, invasive, malignancy that is progressing or required active treatment in the last 5 years.

Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, ductal breast carcinoma in situ, or cervical carcinoma in situ that has undergone potentially curative therapy are not excluded.

  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) Note: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  • Has a known history of active tuberculosis (Bacillus tuberculosis).
  • Has an active infection requiring systemic therapy.
  • Has left ventricular ejection fraction (LVEF) of <50% or below the institution limit of normal, as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed at screening.
  • Has other significant cardiac disease, such as: 1) History of myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass within the last 6 months; or 2) Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA Class III or IV.
  • Has a known history of human immunodeficiency virus (HIV) infection.
  • Has a known history of hepatitis B or known active hepatitis C virus infection.
  • Has received prior treatment for breast cancer.
  • Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137).
  • Has received a live vaccine within 30 days prior to the first dose of study treatment.
  • Has severe hypersensitivity (≥Grade 3) to any of the components or excipients used in the study treatments.
  • Is/was enrolled in a study of an investigational agent and received study therapy, or used an investigational device within 4 weeks (12 months for an investigational agent or device with anticancer or antiproliferative properties) prior to the first dose of study treatment.
  • Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 12 months (for participants who received cyclophosphamide) or 6 months (for participants who did not receive cyclophosphamide) after the last dose of study treatment.
Open or close this module Contacts/Locations
Study Officials: Medical Director
Study Director
Merck Sharp & Dohme LLC
Locations:
Open or close this module IPDSharing
Plan to Share IPD: Yes
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Supporting Information:
Time Frame:
Access Criteria:
URL: http://engagezone.msd.com/ds_documentation.php
Open or close this module References
Citations:
Links:
Available IPD/Information:

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