MedPath

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)

Phase 3
Active, not recruiting
Conditions
Breast Cancer
Interventions
Drug: Placebo (P)
Drug: Endocrine therapy
Radiation: Radiation therapy
Procedure: Surgery
Registration Number
NCT03725059
Lead Sponsor
Merck Sharp & Dohme LLC
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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
1240
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, grade, and PD-L1 status.

Note: Sponsor agreement is required for formalin-fixed paraffin-embedded (FFPE) tumor tissue sample or slides that were obtained greater than 60 days prior to the date that the documented informed consent was obtained.

  • 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Pembrolizumab+Chemotherapy (KX/KA[E]C)Doxorubicin (A)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 either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo 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.
Pembrolizumab+Chemotherapy (KX/KA[E]C)Endocrine therapyIn 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 either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo 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.
Pembrolizumab+Chemotherapy (KX/KA[E]C)Radiation therapyIn 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 either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo 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.
Pembrolizumab+Chemotherapy (KX/KA[E]C)SurgeryIn 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 either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo 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.
Placebo+Chemotherapy (PX/PA[E]C)Placebo (P)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 either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo 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.
Placebo+Chemotherapy (PX/PA[E]C)Paclitaxel (X)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 either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo 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.
Placebo+Chemotherapy (PX/PA[E]C)Doxorubicin (A)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 either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo 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.
Placebo+Chemotherapy (PX/PA[E]C)Epirubicin (E)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 either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo 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.
Placebo+Chemotherapy (PX/PA[E]C)Radiation therapyIn 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 either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo 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.
Placebo+Chemotherapy (PX/PA[E]C)SurgeryIn 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 either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo 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.
Pembrolizumab+Chemotherapy (KX/KA[E]C)Paclitaxel (X)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 either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo 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.
Pembrolizumab+Chemotherapy (KX/KA[E]C)Pembrolizumab (K)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 either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo 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.
Pembrolizumab+Chemotherapy (KX/KA[E]C)Epirubicin (E)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 either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo 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.
Pembrolizumab+Chemotherapy (KX/KA[E]C)Cyclophosphamide (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 either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo 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.
Placebo+Chemotherapy (PX/PA[E]C)Cyclophosphamide (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 either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo 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.
Primary Outcome Measures
NameTimeMethod
Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0Up 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 (8th edition) assessed by the local pathologist at the time of 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.

Event-Free Survival (EFS)Up to approximately 12 years

EFS is defined as the time from randomization to disease progression that: precludes 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
NameTimeMethod
pCR Rate Using the Definition of ypT0ypN0Up 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 (8th edition) assessed by the local pathologist at the time of 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.

pCR Rate Using the Definitions of ypT0/Tis ypN0, ypT0/Tis, and ypT0 ypN0 in Participants With a Combined Positive Score [CPS] ≥1Up 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 (8th edition) assessed by the local pathologist at the time of 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.

OS in Participants With a CPS ≥1Up to approximately 12 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.

Number of Participants Experiencing an Adverse Event (AE)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.

Number of Participants Experiencing a Serious Adverse Event (SAE)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.

Overall Survival (OS)Up to approximately 12 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.

Number of Participants Experiencing an Immune-related AE (irAE)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.

Number of Participants who Discontinued Study Treatment Due to an AEUp to approximately 14 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 discontinue study treatment (pembrolizumab or placebo) due to an AE will be presented.

pCR Rate Using the Definition of ypT0/TisUp 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 (8th edition) assessed by the local pathologist at the time of 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.

EFS in Participants With a CPS ≥1Up to approximately 12 years

EFS is defined as the time from randomization to disease progression that: precludes 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.

Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire Core 30 (QLQ-C30) ScoreBaseline (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.

Change from Baseline in EORTC Breast Cancer-Specific QoL Questionnaire (QLQ-BR23) ScoreBaseline (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.

Trial Locations

Locations (244)

Geisinger Medical Center ( Site 0052)

🇺🇸

Danville, Pennsylvania, United States

Westmead Hospital ( Site 2101)

🇦🇺

Sydney, New South Wales, Australia

Massachusetts General Hospital ( Site 0024)

🇺🇸

Boston, Massachusetts, United States

UZ Leuven ( Site 0702)

🇧🇪

Leuven, Vlaams-Brabant, Belgium

AZ Maria Middelares Gent ( Site 0700)

🇧🇪

Gent, Oost-Vlaanderen, Belgium

ONCOSITE - Centro de Pesquisa Clinica em Oncologia ( Site 0206)

🇧🇷

Ijui, Rio Grande Do Sul, Brazil

CHU UCL Namur Site de Godinne ( Site 0706)

🇧🇪

Yvoir, Namur, Belgium

Associacao Hospitalar Moinhos de Vento ( Site 0201)

🇧🇷

Porto Alegre, Rio Grande Do Sul, Brazil

Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0202)

🇧🇷

Porto Alegre, Rio Grande Do Sul, Brazil

St. Vincent Frontier Cancer Center ( Site 0033)

🇺🇸

Billings, Montana, United States

Clínica Vida Fundación - Sede Poblado ( Site 0405)

🇨🇴

Medellin, Antioquia, Colombia

Rodrigo Botero SAS ( Site 0407)

🇨🇴

Medellin, Antioquia, Colombia

Hospital Metropolitano - Sede Lindora ( Site 4203)

🇨🇷

Santa Ana, San Jose, Costa Rica

Linkou Chang Gung Memorial Hospital ( Site 2402)

🇨🇳

Taoyuan, Taiwan

Dnipropetrovsk City Multidiscipline Clinical Hosp. 4 of DRC ( Site 2702)

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Dnipro, Dnipropetrovska Oblast, Ukraine

Clinica de la Costa Ltda. ( Site 0400)

🇨🇴

Barranquilla, Atlantico, Colombia

Fundacion Universitaria Sanitas ( Site 0403)

🇨🇴

Bogota, Distrito Capital De Bogota, Colombia

Institut Claudius Regaud IUCT Oncopole ( Site 0903)

🇫🇷

Toulouse, Haute-Garonne, France

Institut Curie - Centre Rene Huguenin ( Site 0917)

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Saint-Cloud, Hauts-de-Seine, France

Pecsi Tudomanyegyetem Klinikai Kozpont ( Site 2905)

🇭🇺

Pecs, Baranya, Hungary

Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 2502)

🇵🇹

Porto, Portugal

Centre Francois Baclesse ( Site 0927)

🇫🇷

Caen, Calvados, France

CHR-METZ-THIONVILLE - Hopital de Mercy ( Site 0919)

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Metz, Moselle, France

Bialostockie Centrum Onkologii ( Site 1819)

🇵🇱

Bialystok, Podlaskie, Poland

Fundacao Champalimaud ( Site 2500)

🇵🇹

Lisboa, Aveiro, Portugal

Hospital Geral de Santo Antonio ( Site 2503)

🇵🇹

Porto, Portugal

Oncomedica S.A. ( Site 0401)

🇨🇴

Monteria, Cordoba, Colombia

Khmelnitskiy Regional Onkology Dispensary ( Site 2704)

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Khmelnitskiy, Khmelnytska Oblast, Ukraine

Koo Foundation Sun Yat-Sen Cancer Center ( Site 2403)

🇨🇳

Taipei, Taiwan

St. James s Hospital ( Site 1553)

🇮🇪

Dublin, Ireland

Medical center of the Limited Liability Company Yulis ( Site 2720)

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Zaporizhzhia, Zaporizka Oblast, Ukraine

Communal non profit enterprise Regional Clinical Oncology Center ( Site 2721)

🇺🇦

Kharkiv, Kharkivska Oblast, Ukraine

MI Odesa Regional Clinical Hospital ( Site 2701)

🇺🇦

Odesa, Odeska Oblast, Ukraine

MI Kryviy Rih Center of Dnipropetrovsk Regional Council ( Site 2700)

🇺🇦

Kryviy Rih, Dnipropetrovska Oblast, Ukraine

National Cancer Institute of the MoH of Ukraine ( Site 2719)

🇺🇦

Kyiv, Kyivska Oblast, Ukraine

MI Odessa Regional Oncological Centre ( Site 2714)

🇺🇦

Odesa, Odeska Oblast, Ukraine

Anhui Provincial Hospital ( Site 3224)

🇨🇳

Heifei, Anhui, China

Cancer Hospital Chinese Academy of Medical Sciences ( Site 3208)

🇨🇳

Beijing, Beijing, China

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University ( Site 3213)

🇨🇳

Guangzhou, Guangdong, China

Henan Cancer Hospital ( Site 3212)

🇨🇳

Zhengzhou, Henan, China

Fudan University Shanghai Cancer Center ( Site 3205)

🇨🇳

Shanghai, Shanghai, China

The First Affiliated Hospital of Xi an Jiaotong University ( Site 3220)

🇨🇳

XI An, Shanxi, China

Tianjin Medical University Cancer Institute & Hospital ( Site 3209)

🇨🇳

Tianjin, Tianjin, China

Texas Oncology-Austin Central ( Site 8004)

🇺🇸

Austin, Texas, United States

Texas Oncology-Tyler ( Site 8006)

🇺🇸

Tyler, Texas, United States

Southeastern Regional Medical Center, Inc. ( Site 0075)

🇺🇸

Newnan, Georgia, United States

MGH Newton-Wellesley Hospital's Vernon Cancer Center ( Site 0082)

🇺🇸

Newton, Massachusetts, United States

El Camino Hospital Cancer Center ( Site 0004)

🇺🇸

Mountain View, California, United States

Arizona Oncology Associates PC- HOPE ( Site 8008)

🇺🇸

Tucson, Arizona, United States

Baptist MD Anderson Cancer Center ( Site 0014)

🇺🇸

Jacksonville, Florida, United States

Orchard Healthcare Research Inc. ( Site 0020)

🇺🇸

Skokie, Illinois, United States

The University of Chicago Medical Center ( Site 0080)

🇺🇸

Chicago, Illinois, United States

Ruijin Hosp,Shanghai Jiao Tong University School of Medicine ( Site 3215)

🇨🇳

Shanghai, Anhui, China

Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 8009)

🇺🇸

Dallas, Texas, United States

MercyOne Waterloo Cancer Center ( Site 0016)

🇺🇸

Waterloo, Iowa, United States

Chris OBrien Lifehouse ( Site 2107)

🇦🇺

Camperdown, New South Wales, Australia

Cross Cancer Institute ( Site 0115)

🇨🇦

Edmonton, Alberta, Canada

Clinica de Pesquisas e Ctro de Estudos Onc. Ginecol. e Mamaria Ltda ( Site 0204)

🇧🇷

Sao Paulo, Brazil

Texas Oncology-Dallas Presbyterian Hospital ( Site 8002)

🇺🇸

Dallas, Texas, United States

Texas Oncology-Memorial City ( Site 8012)

🇺🇸

Houston, Texas, United States

Goshen Center for Cancer Care ( Site 0021)

🇺🇸

Goshen, Indiana, United States

Medical Oncology Associates (Summit Cancer Centers) ( Site 0066)

🇺🇸

Spokane, Washington, United States

Centre Oscar Lambret ( Site 0911)

🇫🇷

Lille, Nord-Pas-de-Calais, France

BC Cancer-Vancouver Center ( Site 0116)

🇨🇦

Vancouver, British Columbia, Canada

Centre de Cancerologie du Grand Montpellier ( Site 0925)

🇫🇷

Montpellier, Herault, France

University of Texas-MD Anderson Cancer Center ( Site 0083)

🇺🇸

Houston, Texas, United States

Clinique Victor Hugo ( Site 0906)

🇫🇷

Le Mans, Sarthe, France

Gynaekologisch-onkologische Praxis Hannover ( Site 1013)

🇩🇪

Hannover, Niedersachsen, Germany

Centre Jean Perrin ( Site 0909)

🇫🇷

Clermont Ferrand Cedex, Puy-de-Dome, France

Institut Gustave Roussy ( Site 0926)

🇫🇷

Villejuif, Val-de-Marne, France

Sana Klinikum Offenbach GmbH ( Site 1002)

🇩🇪

Offenbach, Hessen, Germany

Hopital Tenon ( Site 0914)

🇫🇷

Paris, France

Saitama Cancer Center ( Site 2612)

🇯🇵

Kitaadachi-gun, Saitama, Japan

Hopital Saint-Louis ( Site 0908)

🇫🇷

Paris, France

Szent Margit Korhaz ( Site 2901)

🇭🇺

Budapest, Hungary

Gynaekologisches Zentrum ( Site 1003)

🇩🇪

Bonn, Nordrhein-Westfalen, Germany

Universitaetsklinikum Erlangen ( Site 1001)

🇩🇪

Erlangen, Bayern, Germany

Frauenklinik St. Louise ( Site 1014)

🇩🇪

Paderborn, Nordrhein-Westfalen, Germany

Bacs-Kiskun Megyei Korhaz ( Site 2913)

🇭🇺

Kecskemet, Bacs-Kiskun, Hungary

Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 2915)

🇭🇺

Kaposvar, Hungary

MVZ Nordhausen gGmbH - Praxis Dr. Grafe ( Site 1005)

🇩🇪

Nordhausen, Thuringen, Germany

Orszagos Onkologiai Intezet ( Site 2908)

🇭🇺

Budapest, Hungary

Caritas Klinikum Saarbruecken St. Theresia ( Site 1009)

🇩🇪

Saarbruecken, Saarland, Germany

Uzsoki Utcai Korhaz ( Site 2902)

🇭🇺

Budapest, Hungary

Bon Secours Hospital ( Site 1554)

🇮🇪

Cork, Ireland

Universitaetsklinikum Carl Gustav Carus ( Site 1008)

🇩🇪

Dresden, Sachsen, Germany

Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi OktatoKorhaz ( Site 2904)

🇭🇺

Miskolc, Borsod-Abauj-Zemplen, Hungary

HaEmek Medical Center ( Site 1712)

🇮🇱

Afula, Israel

Instytut Centrum Zdrowia Matki Polki ( Site 1821)

🇵🇱

Lodz, Lodzkie, Poland

Kitasato University Hospital ( Site 2616)

🇯🇵

Sagamihara, Kanagawa, Japan

Hyogo College of Medicine Hospital ( Site 2600)

🇯🇵

Nishinomiya, Hyogo, Japan

Assuta Ashdod Public ( Site 1704)

🇮🇱

Ashdod, Israel

Rambam Health Care Campus-Oncology Division ( Site 1705)

🇮🇱

Haifa, Israel

Showa University Hospital ( Site 2615)

🇯🇵

Tokyo, Japan

Shaare Zedek Medical Center ( Site 1708)

🇮🇱

Jerusalem, Israel

Meir Medical Center ( Site 1710)

🇮🇱

Kfar-Saba, Israel

Fukushima Medical University Hospital ( Site 2610)

🇯🇵

Fukushima, Japan

Capital & Coast District Health Board - Wellington Hospital ( Site 2301)

🇳🇿

Wellington, New Zealand

Mazowiecki Szpital Specjalistyczny im. dr Jozefa Psarskiego ( Site 1814)

🇵🇱

Ostroleka, Mazowieckie, Poland

Shizuoka Cancer Center Hospital and Research Institute ( Site 2611)

🇯🇵

Sunto-gun, Shizuoka, Japan

Mazowiecki Szpital Onkologiczny ( Site 1803)

🇵🇱

Wieliszew, Mazowieckie, Poland

Hadassah Ein Karem - Sharett Institute of Oncology ( Site 1700)

🇮🇱

Jerusalem, Israel

Holy Family Hospital ( Site 1711)

🇮🇱

Nazareth, Israel

Kaplan Medical Center ( Site 1703)

🇮🇱

Rehovot, Israel

Assuta Medical Center ( Site 1709)

🇮🇱

Tel Aviv, Israel

National Cancer Center Hospital East ( Site 2613)

🇯🇵

Kashiwa, Chiba, Japan

Chiba Cancer Center ( Site 2605)

🇯🇵

Chiba, Japan

National Cancer Center ( Site 2204)

🇰🇷

Goyang-si, Kyonggi-do, Korea, Republic of

Asan Medical Center ( Site 2202)

🇰🇷

Songpagu, Seoul, Korea, Republic of

Sourasky Medical Center ( Site 1706)

🇮🇱

Tel Aviv, Israel

Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1800)

🇵🇱

Bydgoszcz, Kujawsko-pomorskie, Poland

Samsung Medical Center ( Site 2203)

🇰🇷

Seoul, Korea, Republic of

CHLN Hospital Santa Maria ( Site 2501)

🇵🇹

Lisboa, Portugal

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (

🇵🇱

Warszawa, Mazowieckie, Poland

Arkhangelsk Clinical Oncological Dispensary ( Site 1901)

🇷🇺

Arkhangelsk, Arkhangel Skaya Oblast, Russian Federation

Hospital Teresa Herrera - Chuac ( Site 1358)

🇪🇸

A Coruna, La Coruna, Spain

Hospital Quiron de Madrid ( Site 1351)

🇪🇸

Pozuelo de Alarcon, Madrid, Spain

Wojewodzkie Centrum Onkologii Copernicus ( Site 1817)

🇵🇱

Gdansk, Pomorskie, Poland

Szpitale Pomorskie Sp. z o.o. ( Site 1818)

🇵🇱

Gdynia, Pomorskie, Poland

N.N. Blokhin NMRCO ( Site 1908)

🇷🇺

Moscow, Moskva, Russian Federation

Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1909)

🇷🇺

Ufa, Baskortostan, Respublika, Russian Federation

Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu ( Site 1807)

🇵🇱

Bytom, Slaskie, Poland

Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 1363)

🇪🇸

Hospitalet de Llobregat, Barcelona, Spain

Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 1801)

🇵🇱

Gliwice, Slaskie, Poland

UPR Comprehensive Cancer Center ( Site 6200)

🇵🇷

San Juan, Puerto Rico

China Medical University Hospital ( Site 2401)

🇨🇳

Taichung, Taiwan

National Cheng Kung University Hospital ( Site 2400)

🇨🇳

Tainan, Taiwan

Instituto Oncologico Baselga.Hospital Quiron. ( Site 1352)

🇪🇸

Barcelona, Spain

Complejo Hospitalario de Jaen ( Site 1364)

🇪🇸

Jaen, Spain

Hospital Ruber Internacional ( Site 1370)

🇪🇸

Madrid, Spain

Hospital Clinico San Carlos ( Site 1354)

🇪🇸

Madrid, Spain

National Taiwan University Hospital ( Site 2404)

🇨🇳

Taipei, Taiwan

Hospital Clinic I Provincial de Barcelona ( Site 1353)

🇪🇸

Barcelona, Spain

Hospital Clinico Universitario de Valencia ( Site 1355)

🇪🇸

Valencia, Valenciana, Comunitat, Spain

Communal nonprofit enterprise "Kherson Regional Oncology Dispensary" of Kherson Regional Council (

🇺🇦

Antonivka Village, Khersonska Oblast, Ukraine

Colchester General Hospital ( Site 1508)

🇬🇧

Colchester, Essex, United Kingdom

Barts Health NHS Trust ( Site 1500)

🇬🇧

London, London, City Of, United Kingdom

University Hospitals Bristol NHS Foundation Trust ( Site 1503)

🇬🇧

Bristol, Bristol, City Of, United Kingdom

Kyiv City Clinical Oncology Centre ( Site 2716)

🇺🇦

Kyiv, Ukraine

Guy's Hospital ( Site 1501)

🇬🇧

London, London, City Of, United Kingdom

St. Georges University Hospital NHS Foundation Trust ( Site 1505)

🇬🇧

London, London, City Of, United Kingdom

Toranomon Hospital ( Site 2608)

🇯🇵

Tokyo, Japan

Saitama Medical University International Medical Center ( Site 2606)

🇯🇵

Hidaka, Saitama, Japan

Kumamoto University Hospital ( Site 2602)

🇯🇵

Kumamoto, Japan

The Cancer Institute Hospital of JFCR ( Site 2604)

🇯🇵

Tokyo, Japan

Hospital Vall D Hebron ( Site 1357)

🇪🇸

Barcelona, Spain

Klinikum der Universitaet Muenchen - Grosshadern ( Site 1000)

🇩🇪

Muenchen, Bayern, Germany

Hospital Universitario 12 de Octubre ( Site 1356)

🇪🇸

Madrid, Spain

Hospital Universitario Virgen del Rocio ( Site 1360)

🇪🇸

Sevilla, Spain

Hospital General Arnau de Vilanova de Valencia ( Site 1369)

🇪🇸

Valencia, Spain

Ryazan Regional Clinical Oncology Dispensary ( Site 1910)

🇷🇺

Ryazan, Ryazanskaya Oblast, Russian Federation

Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1903)

🇷🇺

Kazan, Tatarstan, Respublika, Russian Federation

Tomsk Scientific Research Institute of Oncology ( Site 1905)

🇷🇺

Tomsk, Tomskaya Oblast, Russian Federation

Rabin Medical Center ( Site 1702)

🇮🇱

Petah Tikva, Israel

Chaim Sheba Medical Center. ( Site 1707)

🇮🇱

Ramat Gan, Israel

Texas Oncology- Plano East ( Site 8010)

🇺🇸

Plano, Texas, United States

University of Colorado Cancer Center ( Site 0008)

🇺🇸

Aurora, Colorado, United States

Maryland Oncology Hematology, P.A. ( Site 8007)

🇺🇸

Bethesda, Maryland, United States

Mayo Clinic and Medical School (Rochester) ( Site 0029)

🇺🇸

Rochester, Minnesota, United States

Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0039)

🇺🇸

Omaha, Nebraska, United States

OHSU Knight Cancer Institute ( Site 0051)

🇺🇸

Portland, Oregon, United States

Virginia Oncology Associates ( Site 8001)

🇺🇸

Norfolk, Virginia, United States

Canterbury Regional Cancer & Blood Services ( Site 2303)

🇳🇿

Christchurch, Canterbury, New Zealand

Southern Cancer Center, PC ( Site 8003)

🇺🇸

Daphne, Alabama, United States

Cedars Sinai Medical Center Samuel Oschin Comp. Cancer Institute ( Site 0079)

🇺🇸

Los Angeles, California, United States

Cancer Treatment Centers of America at Western Regional Medical Center ( Site 0001)

🇺🇸

Goodyear, Arizona, United States

Stanford Cancer Center ( Site 0072)

🇺🇸

Palo Alto, California, United States

Midwestern Regional Medical Center, Inc. ( Site 0077)

🇺🇸

Zion, Illinois, United States

Henry Ford Health System ( Site 0028)

🇺🇸

Detroit, Michigan, United States

MGH - North Shore Cancer Center ( Site 0081)

🇺🇸

Danvers, Massachusetts, United States

Weill Cornell Medical College ( Site 0043)

🇺🇸

New York, New York, United States

Holy Name Medical Center ( Site 0041)

🇺🇸

Teaneck, New Jersey, United States

CTCA Southwestern ( Site 0074)

🇺🇸

Tulsa, Oklahoma, United States

Northwest Cancer Specialists, P.C. ( Site 8000)

🇺🇸

Tigard, Oregon, United States

Fox Chase Cancer Center ( Site 0078)

🇺🇸

Philadelphia, Pennsylvania, United States

Cancer Treatment Centers of America-Eastern Regional Medical Center ( Site 0076)

🇺🇸

Philadelphia, Pennsylvania, United States

Medical University of South Carolina ( Site 0053)

🇺🇸

Charleston, South Carolina, United States

Tennessee Oncology, PLLC/The Sarah Cannon Research Institute ( Site 7000)

🇺🇸

Nashville, Tennessee, United States

Bon Secours St. Francis Medical Center Oncology Research ( Site 0064)

🇺🇸

Midlothian, Virginia, United States

Kadlec Clinic Hematology and Oncology ( Site 0070)

🇺🇸

Kennewick, Washington, United States

Royal North Shore Hospital ( Site 2100)

🇦🇺

Sydney, New South Wales, Australia

Frankston Hospital ( Site 2103)

🇦🇺

Frankston, Victoria, Australia

Mater Misericordiae Ltd ( Site 2106)

🇦🇺

South Brisbane, Queensland, Australia

Peter MacCallum Cancer Centre ( Site 2102)

🇦🇺

Melbourne, Victoria, Australia

Jessa Ziekenhuis Campus Virga Jesse ( Site 0704)

🇧🇪

Hasselt, Limburg, Belgium

CHC MontLegia ( Site 0707)

🇧🇪

Liège, Liege, Belgium

Cliniques Universitaires Saint-Luc ( Site 0701)

🇧🇪

Brussels, Bruxelles-Capitale, Region De, Belgium

AZ Groeninge ( Site 0705)

🇧🇪

Kortrijk, West-Vlaanderen, Belgium

Hospital Araujo Jorge Associacao de Combate ao Cancer de Goias ( Site 0205)

🇧🇷

Goiania, Goias, Brazil

CEPON - Centro de Pesquisas Oncologicas ( Site 0208)

🇧🇷

Florianopolis, Santa Catarina, Brazil

Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 0207)

🇧🇷

Itajai, Santa Catarina, Brazil

Instituto Nacional de Cancer - INCA HC III ( Site 0200)

🇧🇷

Rio de Janeiro, Brazil

Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0209)

🇧🇷

Sao Paulo, Brazil

Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 0210)

🇧🇷

São Paulo, Sao Paulo, Brazil

CHU de Quebec Universite Laval - Hopital du Saint-Sacrement ( Site 0101)

🇨🇦

Quebec, Canada

Hopital Maisonneuve-Rosemont CIUSSS de l Est de L Ile de Montreal ( Site 0111)

🇨🇦

Montreal, Quebec, Canada

Centre Hospitalier Regional de Trois-Rivieres ( Site 0106)

🇨🇦

Trois-Rivières, Quebec, Canada

Princess Margaret Cancer Centre ( Site 0112)

🇨🇦

Toronto, Ontario, Canada

CISSS de la Monteregie-Centre ( Site 0108)

🇨🇦

Greenfield Park, Quebec, Canada

Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0114)

🇨🇦

Montreal, Quebec, Canada

Jewish General Hospital ( Site 0103)

🇨🇦

Montreal, Quebec, Canada

Harbin Medical University Cancer Hospital ( Site 3200)

🇨🇳

Harbin, Heilongjiang, China

Fujian Medical University Union Hospital-1 Bingfanglou-Oncology ( Site 3207)

🇨🇳

Fuzhou Fujian, Fujian, China

The First Affiliated Hospital of Zhejiang University ( Site 3203)

🇨🇳

Hangzhou, Jiangsu, China

Hubei Cancer Hospital ( Site 3211)

🇨🇳

Wuhan, Hubei, China

Fourth Hospital Of Hebei Medical University ( Site 3216)

🇨🇳

Shijia Zhuang, Hebei, China

Hunan Cancer Hospital ( Site 3214)

🇨🇳

Changsha, Hunan, China

The First Hospital of Jilin University ( Site 3201)

🇨🇳

Changchun, Jilin, China

Zhejiang Cancer Hospital.... ( Site 3210)

🇨🇳

Hangzhou, Zhejiang, China

Zhejiang Provincial People's Hospital ( Site 3225)

🇨🇳

Hangzhou, Zhejiang, China

Cancer Hospital Affiliated to Xinjiang Medical University ( Site 3219)

🇨🇳

Urumqi, Xinjiang, China

Centro de Investigacion Clinica del Country ( Site 0402)

🇨🇴

Bogota, Distrito Capital De Bogota, Colombia

Centro Medico Imbanaco de Cali S.A ( Site 0406)

🇨🇴

Cali, Valle Del Cauca, Colombia

Institut Sainte Catherine ( Site 0916)

🇫🇷

Avignon, Provence-Alpes-Cote-d Azur, France

Centre Georges Francois Leclerc ( Site 0920)

🇫🇷

Dijon, Cote-d Or, France

Institut Curie ( Site 0900)

🇫🇷

Paris, France

Medizinische Management GmbH ( Site 1012)

🇩🇪

Friedrichshafen, Baden-Wurttemberg, Germany

HELIOS Dr. Horst Schmidt Kliniken Wiesbaden ( Site 1004)

🇩🇪

Wiesbaden, Hessen, Germany

Kliniken Essen Mitte Gmbh Evang. Huyssens Stiftung ( Site 1006)

🇩🇪

Essen, Nordrhein-Westfalen, Germany

Debreceni Egyetem Klinikai Kozpont ( Site 2907)

🇭🇺

Debrecen, Hungary

Soroka Medical Center ( Site 1701)

🇮🇱

Beer Sheva, Israel

National Hospital Organization Hokkaido Cancer Center ( Site 2607)

🇯🇵

Sapporo, Hokkaido, Japan

Aichi Cancer Center Hospital ( Site 2601)

🇯🇵

Nagoya, Aichi, Japan

National Hospital Organization - Osaka National Hospital - Institute For Clinical Research ( Site 26

🇯🇵

Osaka, Japan

Hiroshima City Hiroshima Citizens Hospital ( Site 2603)

🇯🇵

Hiroshima, Japan

Tauranga Hospital ( Site 2302)

🇳🇿

Tauranga, Bay Of Plenty, New Zealand

Severance Hospital Yonsei University Health System ( Site 2201)

🇰🇷

Seoul, Korea, Republic of

Dolnoslaskie Centrum Onkologii. ( Site 1820)

🇵🇱

Wrocław, Dolnoslaskie, Poland

Seoul National University Hospital ( Site 2200)

🇰🇷

Seoul, Korea, Republic of

Medical Rehabilitation Center ( Site 1912)

🇷🇺

Moscow, Moskva, Russian Federation

Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1900)

🇷🇺

Saint Petersburg, Sankt-Peterburg, Russian Federation

Central Clinical Hospital with outpatient Clinic ( Site 1907)

🇷🇺

Moscow, Moskva, Russian Federation

Railway Hospital of OJSC ( Site 1913)

🇷🇺

Saint Petersburg, Sankt-Peterburg, Russian Federation

Hospital General Universitario Gregorio Maranon ( Site 1367)

🇪🇸

Madrid, Madrid, Comunidad De, Spain

Birmingham & Solihull Heartlands Hospital NHS ( Site 1506)

🇬🇧

Solihull, United Kingdom

Royal Cornwall Hospital ( Site 1502)

🇬🇧

Truro, United Kingdom

UC Davis Comprehensive Cancer Center ( Site 0073)

🇺🇸

Sacramento, California, United States

James Graham Brown Cancer Center ( Site 0022)

🇺🇸

Louisville, Kentucky, United States

Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 1810)

🇵🇱

Bielsko-Biala, Slaskie, Poland

Institut Jules Bordet ( Site 0710)

🇧🇪

Anderlecht, Bruxelles-Capitale, Region De, Belgium

Imelda Ziekenhuis Bonheiden ( Site 0703)

🇧🇪

Bonheiden, Antwerpen, Belgium

UZ Antwerpen - Medical Oncology ( Site 0709)

🇧🇪

Edegem, Antwerpen, Belgium

MI Precarpathian Clinical Oncology Center ( Site 2707)

🇺🇦

Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine

Nottingham University Hospitals NHS Trust ( Site 1504)

🇬🇧

Nottingham, England, United Kingdom

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