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)

• Register: ClinicalTrials.gov
• Last refreshed on: 10 July 2023
• Main ID: NCT03036488
• Date of registration: 27/01/2017
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme LLC
• Public title: 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)
• Scientific title: 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)
• Date of first enrolment: March 7, 2017
• Target sample size: 1174
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT03036488
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Australia, Belgium, Brazil, Canada, Chile, Colombia, Denmark, France, Germany, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, New Zealand, Peru, Poland, Portugal, Russian Federation, Singapore, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Merck Sharp & Dohme LLC

Key inclusion & exclusion criteria

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).



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Triple Negative Breast Neoplasms

Intervention(s)

Drug: Epirubicin

Drug: Paclitaxel

Drug: Carboplatin

Drug: Cyclophosphamide

Drug: Placebo

Drug: Doxorubicin

Biological: Granulocyte colony stimulating factor: Filgrastim or Pegfilgastrim

Biological: Pembrolizumab

Primary Outcome(s)

Pathological complete response (pCR) rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery [Time Frame: Up to approximately 27-30 weeks]

Event-free Survival (EFS) as assessed by Investigator [Time Frame: Up to approximately 8 years]

Secondary Outcome(s)

pCR rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery [Time Frame: Up to approximately 27-30 weeks]

European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 Questionnaire (QLQ-C30) score [Time Frame: Up to approximately 27-30 weeks]

EORTC Breast Cancer-Specific QoL Questionnaire (QLQ-BR23) score [Time Frame: Up to approximately 27-30 weeks]

Percentage of participants who discontinue study treatment due to an AE [Time Frame: Up to approximately 57 weeks]

EFS in participants with tumors expressing PD-L1 [Time Frame: Up to approximately 8 years]

Overall survival (OS) [Time Frame: Up to approximately 8 years]

pCR rate using an alternative definition, ypT0 ypN0 (i.e., no invasive or noninvasive residual in breast or nodes) at the time of definitive surgery [Time Frame: Up to approximately 27-30 weeks]

pCR rate using an alternative definition, ypT0/Tis (i.e., absence of invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement) at the time of definitive surgery [Time Frame: Up to approximately 27-30 weeks]

Percentage of participants who experience an adverse event (AE) [Time Frame: Up to approximately 61 weeks]

Secondary ID(s)

KEYNOTE-522

MK-3475-522

173567

2016-004740-11

3475-522

Source(s) of Monetary Support

Please refer to primary and secondary sponsors