Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs Placebo Plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy in Participants With Triple Negative Breast Cancer (TNBC) (MK-3475-522/KEYNOTE-522)



Status:Active, not recruiting
Conditions:Breast Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:1/31/2019
Start Date:March 7, 2017
End Date:September 30, 2025

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A Phase III, Randomized, Double-blind Study to Evaluate Pembrolizumab Plus Chemotherapy vs Placebo Plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy for Triple Negative Breast Cancer (TNBC)

The purpose of this study is to evaluate the efficacy and safety of pembrolizumab (MK-3475)
plus chemotherapy vs placebo plus chemotherapy as neoadjuvant therapy and pembrolizumab vs
placebo as adjuvant therapy in participants who have triple negative breast cancer (TNBC).

After a screening phase of approximately 28 days, each participant will receive neoadjuvant
study treatment (Pembrolizumab + Chemotherapy OR Placebo + Chemotherapy) based on the
randomization schedule for approximately 24 weeks (8 cycles). Each participant will then
undergo definitive surgery 3-6 weeks after conclusion of the last cycle of the neoadjuvant
study treatment. After definitive surgery, each participant will receive adjuvant study
treatment (Pembrolizumab OR Placebo) for approximately 27 weeks (9 cycles). Following
adjuvant study treatment, each participant will be monitored for safety, survival and disease
recurrence.

The primary study hypothesis is that pembrolizumab is superior to placebo, in combination
with chemotherapy, as measured by the rate of Pathological Complete Response (pCR) and/or
Event-free Survival (EFS), in participants with locally advanced TNBC.


Inclusion Criteria:

- Has newly diagnosed, locally advanced, centrally confirmed TNBC, as defined by the
most recent American Society of Clinical Oncology (ASCO)/College of American
Pathologists (CAP) guidelines.

- Has previously untreated locally advanced non-metastatic (M0) TNBC defined as the
following combined primary tumor (T) and regional lymph node (N) staging per current
American Joint Committee of Cancer (AJCC) staging criteria for breast cancer as
assessed by the investigator based on radiological and/or clinical assessment:

- T1c, N1-N2

- T2, N0-N2

- T3, N0-N2

- T4a-d, N0-N2

- Provides a core needle biopsy consisting of at least 2 separate tumor cores from the
primary tumor at screening to the central laboratory.

- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed
within 10 days of treatment initiation.

- Demonstrates adequate organ function.

- Males and female participants of childbearing potential must be willing to use an
adequate method of contraception for the course of the study through 12 months after
the last dose of study treatment for participants who have received cyclophosphamide,
and 6 months after the last dose of study treatment for participants who did not.

Exclusion Criteria:

- Has a history of invasive malignancy ≤5 years prior to signing informed consent except
for adequately treated basal cell or squamous cell skin cancer or in situ cervical
cancer.

- Has received prior chemotherapy, targeted therapy, and radiation therapy within the
past 12 months.

- Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1),
anti-programmed death - ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent
directed to another co-inhibitory T-cell receptor (e.g., cytotoxic
T-lymphocyte-associated antigen-4 [CTLA-4], OX-40, CD137 [tumor necrosis factor
receptor superfamily member 9 (TNFRSF9)]) or has previously participated in a
pembrolizumab (MK-3475) clinical study.

- Is currently participating in or has participated in an interventional clinical study
with an investigational compound or device within 4 weeks of the first dose of
treatment in this current study.

- Has received a live vaccine within 30 days of the first dose of study treatment.

- Has an active autoimmune disease that has required systemic treatment in past 2 years
(i.e., with use of disease modifying agents, corticosteroids or immunosuppressive
drugs).

- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (i.e.,
dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study treatment.

- Has a known history of Human Immunodeficiency Virus (HIV).

- Has known active Hepatitis B or Hepatitis C.

- Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.

- Has an active infection requiring systemic therapy.

- Has significant cardiovascular disease, such as: history of myocardial infarction,
acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the
last 6 months OR congestive heart failure (CHF) New York Heart Association (NYHA)
Class II-IV or history of CHF NYHA Class III or IV.

- Is pregnant or breastfeeding, or expecting to conceive children within the projected
duration of the study, starting with the screening visit through 12 months after the
last dose of study treatment for participants who have received cyclophosphamide, and
for 6 months after the last dose of study treatment for participants who have not.

- Has a known hypersensitivity to the components of the study treatment or its analogs.

- Has a known history of active tuberculosis (TB, Bacillus Tuberculosis).
We found this trial at
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Charlottesville, Virginia 22903
(434) 924-0311
Phone: 434-243-0425
University of Virginia The University of Virginia is distinctive among institutions of higher education. Founded...
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4805 Northeast Glisan Street
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593 Eddy Street
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825 Eastlake Ave E
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Aurora, Colorado 80045
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Austin, Texas 78731
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5841 S Maryland Ave
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5053 Wooster Rd
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Oncology Hematology Care Our more than 60 physicians and advanced practice providers throughout neighborhood offices...
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375 Dixmyth Ave
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Dallas, Texas 75235
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2201 Inwood Rd
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5323 Harry Hines Boulevard
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2799 W Grand Blvd
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Evanston, Illinois 60201
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8503 Arlington Blvd., Ste. 400
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400 West Magnolia Avenue
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333 Cedar St
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5900 Lake Wright Dr
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Virginia Oncology Associates Virginia Oncology Associates is an oncology and hematology practice of physicians, specializing...
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