Trial for Treatment of High Risk BC With Two Sequences of Neoadjuvant Chemotherapy With Pembrolizumab

Inclusion Criteria: Participants are eligible to be included in the study only if all the following criteria apply: 1. Be willing and able to provide written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research. 2. Be a female or male participant who is at least 18 years of age on the day of signing informed consent. 3. Have locally histologically confirmed diagnosis of invasive carcinoma of the breast that is classified as TNBC, as defined by the most recent ASCO/CAP guidelines. 4. Has locally confirmed tumor infiltrating lymphocytes (stromal) (sTILs) equal to or above 10%, as defined by the most recent International Guidelines on TIL Assessment in Breast Cancer. 5. Have previously untreated non-metastatic (M0) TNBC defined as the following combined primary tumor (T) and regional lymph node (N) staging per current AJCC staging criteria for breast cancer staging criteria as assessed by the investigator based on radiological and/or clinical assessment: 1. T1c, N1-N2 2. T2, N0-N2 3. T3, N0-N2 4. T4a-d, N0-N2 Note: bilateral tumors (ie, synchronous cancers in both breasts) and/or multi-focal (ie, 2, separate lesions in the same quadrant)/multi-centric (ie, 2 separate lesions in different quadrants) tumors are allowed, as well as inflammatory breast cancer, and the tumor with the most advanced T stage should be used to assess the eligibility. If the subject has either bilateral or multi-focal/multi-centric disease, TNBC needs to be confirmed in at least 2 lesions/breast/focus. Beyond this rule, the extent of tumor biopsy confirmation is based on the best clinical judgment by local investigators. 6. Provide a core needle biopsy consisting of at least 3 separate tumor cores from the primary tumor at screening to the designated central biobank (or responsible laboratories) and is willing to provide a second biopsy at the end of the first cycle of treatment. Note: Detailed instructions on sample collection, processing, storage and shipment to the central biobank are provided in the Laboratory Manual. 7. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days of treatment initiation. 8. Have left ventricular ejection fraction (LVEF) of ≥50% or ≥ institution lower limit of normal (LLN) as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed at screening. 9. Have adequate organ function as defined in the following table (Table 2). Specimens must be collected within 28 days prior to the start of study intervention. 10. Male participants: A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 12 months after the last dose of cyclophosphamide or 6 months after last chemotherapy (whichever occurs last) and refrain from donating sperm during this period. Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 12 months after the last dose of cyclophosphamide or 6 months after last chemotherapy (whichever occurs last). \- Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: 1. 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. 2. Has received prior chemotherapy, targeted therapy, and radiation therapy within the past 12 months. 3. 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 (eg, CTLA-4, OX-40, CD137). 4. Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 4 weeks of the first dose of treatment in this current trial. Note: subject should be excluded if he/she received an investigational agent with anticancer or anti-proliferative intent within the last 12 months. 5. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed. 6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in 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 drug. 7. Has 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). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. 8. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. 9. Has significant cardiovascular disease, such as: 1. History of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the last 6 months 2. Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA class III or IV 10. Has a known history of Human Immunodeficiency Virus (HIV) infection. 11. 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. 12. Has a known history of active TB (Bacillus Tuberculosis). 13. Has an active infection requiring systemic therapy. 14. If surgery was performed prior to screening, has persistent adverse events or incomplete wound healing considered clinically relevant by the treating investigator. 15. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. 16. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 17. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through at least 12 months after the last dose of cyclophosphamide or 6 months after last chemotherapy (whichever occurs last). 18. Has had an allogenic tissue/solid organ transplant. 19. Subjects without legal capacity who are unable to understand the nature, scope, significance and consequences of this clinical trial and to consent