This is a randomized, placebo-controlled, parallel-group, multisite, double-blind study to
evaluate pembrolizumab plus chemotherapy versus placebo plus chemotherapy as
neoadjuvant treatment, followed by pembrolizumab plus endocrine therapy versus placebo
plus endocrine therapy as adjuvant treatment for high-risk early-stage ER+/HER2– breast
To compare the rate of pathological complete response (pCR) at the time of definitive surgery, using the definition of ypT0/Tis ypN0 as assessed by the local pathologist, of pembrolizumab versus placebo, both in combination with the protocol-specified neoadjuvant anticancer therapies. Hypothesis (H1): Pembrolizumab is superior to placebo, both in combination with the protocol-specified neoadjuvant anticancer therapy, as assessed by pCR defined as ypT0/Tis ypN0 defined by the local pathologist.
Experimental: Neoadjuvant Treatment Period: Pembrolizumab + Paclitaxel + Doxorubicin
Pembrolizumab (K) every 3 weeks (Q3W) + paclitaxel (X) once weekly (QW) for 4 cycles (Treatment 1), followed by pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) for 4 cycles (Treatment 2). At the investigator’s discretion, the AC/EC regimen can be administered every 2 weeks (Q2W; dosedense) or Q3W.
Active Comparator: Neoadjuvant Treatment Period: Placebo
Placebo (P) Q3W + paclitaxel (X) QW for 4 cycles (Treatment 1) followed by placebo + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) for 4 cycles (Treatment 2). At the investigator’s discretion, the AC/EC regimen can be administered Q2W (dose-dense) or Q3W.
Experimental: Adjuvant Period: Pembrolizumab + Endocrine Therapy
Pembrolizumab Q3W for 9 cycles + endocrine therapy for up to 10 years.
Active Comparator: Adjuvant Period: Placebo + Endocrine Therapy
Placebo Q3W for 9 cycles + endocrine therapy for up to 10 years.
Baptist MD Anderson Cancer Center
- Participant 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.
- 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.
- Is a male or female ≥18 years of age on the day of signing informed consent.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 10 days prior to initiation of study treatment
- A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding
- The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for future biomedical research. However the participant may participate in the main study without participating in future biomedical research.
- Absolute Neutrophil Count > 1,500 cells/uL
- Platelets > 100,000 cells/uL
- Hemoglobin > 9 g/dL or > 5.6 mmol/L
- Creatinine < 1.5 x ULN
- Total Bilirubin < 1.5 x ULN
- AST < 2.5 x ULN
- 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 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.
- Participants who have undergone excisional biopsy of the primary tumor and/or axillary lymph nodes or have 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.
- 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 (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs)
- Has a known history of active tuberculosis (Bacillus tuberculosis).
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition (eg, transfusion-dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that is specifically contraindicated per the current locally-approved labeling, that might confound the results of the trial, interfere with the participant’s involvement for the full duration of the trial, or is not in the best interest of the participant to be involved, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would may interfere with cooperation with the requirements of the trial.
- 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 a known history of human immunodeficiency virus (HIV) infection.
- Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus.