High-Risk Early-Stage Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2–) Breast Cancer MedDRA version: 23.0 Level: LLT Classification code 10070575 Term: Estrogen receptor positive breast cancer System Organ Class: 100000004864
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Type of Participant and Disease Characteristics 1. 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. 2. 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. 3. 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. Demographics 4. Is a male or female =18 years of age on the day of signing informed consent. 5. 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: 6. A male participant must agree to use a contraception as detailed in Appendix 3 of the protocol 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: 7. A female participant is eligible to participate if she is not pregnant , not breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) OR b.) A WOCBP who agrees to follow the contraceptive guidance 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. Informed Consent 8. The participant (or legally acceptable representative if applicable) provides documented 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. Laboratory Evaluations 9. Has adequate organ function, as detailed in the protocol; all screening laboratory tests should be performed within 10 days prior to initiation of study treatment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 855 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 285
Exclusion criteria
Exclusion criteria: Medical Conditions 1. Has a history of non-infectious pneumonitis that required treatment with steroids or has current pneumonitis. 2. Has breast cancer with lobular histology. 3. Has bilateral invasive breast cancer. 4. Has metastatic (Stage IV) breast cancer. 5. Has multi-centric breast cancer (presence of more than 1 tumor in different quadrants of the breast). 6. 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. 7. Has ER–, progesterone receptor positive breast cancer. 8. 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. 9. Has a known additional, invasive, malignancy that is progressing or required active treatment in the last 5 years. 10. 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. 11. 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) 12. Has a known history of active tuberculosis (Bacillus tuberculosis). 13. Has an active infection requiring systemic therapy. 14. 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 study, interfere with the participant’s involvement for the full duration of the study, or is not in the best interest of the participant to be involved, in the opinion of the treating investigator. 15. Has known psychiatric or substance abuse disorders that would may interfere with cooperation with the requirements of the study. 16. 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. 17. Has other significant cardiac disease, such as: - History of myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass within the last 6 months; - Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA Class III or IV. 18. Has a known history of human immunodeficiency virus (HIV) infection. 19. Has a known history of hepatitis B (defined as hepatitis B surface antigen [HbsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. 20. A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of study treatment. If the urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Prior/Concomitant Therapy 21. Has received prior treatment for breast cancer. 22. Has received prior therapy with an anti-PD-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., CTLA-4, OX 40, CD137). 23. Has received a live vaccine within 30 days prior to the first dose of study treatment. Examp
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the rate of pathological complete response (pCR) at the time of 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. To compare event-free survival (EFS) following administration of pembrolizumab and placebo, both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies, as determined by the investigator.;Secondary Objective: 1.To compare: -OS following administration of pembrolizumab and placebo, both in combination with the neoadjuvant and adjuvant therapies -rate of pCR at surgery, using ypT0 ypN0 and ypT0/Tis as assessed by local pathologist, of pembrolizumab vs placebo, both in combination with neoadjuvant therapies -rate of pCR at surgery, using ypT0/Tis ypN0, ypT0 ypN0, and ypT0/Tis as assessed by local pathologist, of pembrolizumab vs placebo, both in combination with neoadjuvant therapies in sbj with PD-L1+ tumors (CPS =1) -EFS as determined by investigator and OS following administration of pembrolizumab and placebo, both in combination with neoadjuvant and adjuvant therapies, in sbj with PD-L1+ tumors (CPS =1) 2.To evaluate safety and tolerability of pembrolizumab plus neoadjuvant chemotherapy and adjuvant endocrine therapy, and health related quality-of-life (QoL) assessments using QLQC30 and QLQ-BR23, within and across neoadjuvant and adjuvant periods ;Primary end point(s): Pathological Complete Response Rate (ypT0/Tis ypN0) Event-Free Survival;Timepoint(s) of evaluation of this end point: After Surgery and at any point PD/recurrance occur | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Survival Pathological Complete Response Rate (ypT0 ypN0);Timepoint(s) of evaluation of this end point: After Surgery and at any point PD/recurrance occur | — |
Countries
Australia, Belgium, Brazil, Canada, Colombia, France, Germany, Hungary, Ireland, Israel, Japan, Korea, Republic of, New Zealand, Poland, Portugal, Russian Federation, Spain, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactGCTO
Merck Sharp & Dohme, Lda.
Outcome results
None listed