Novel Neoadjuvant and Adjuvant Strategy for Germline BRCA 1/2 Mutated Triple Negative Breast Cancer

Prior treatment

• Subjects who has a positive urine pregnancy test within 72 hours prior to registration
• 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 .
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and investigational drugs used in this study and/or any of their excipients.
• Has had an allogenic tissue/solid organ transplant.
• Has received pre-treatment with Olaparib or other PARP inhibitors.
• Subject received colony-stimulating factors within 28 days prior to the first dose of study intervention.
• Is currently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study.
• Is currently receiving either strong or moderate inducers of CYP3A4 that cannot be discontinued for the duration of the study.

Other illness

• Has diagnosed as inflammatory breast cancer.
• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
• Has active autoimmune disease that has required systemic treatment in the past 2 years
• Has a history of (non-infectious) pneumonitis/interstitial lung disease .
• Has an active infection requiring systemic therapy.
• 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 (defined as HCV RNA \[qualitative\] is detected) infection.
• Has a known history of active TB (Bacillus Tuberculosis).
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Has significant cardiovascular disease
• Has a resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions.
• Subject has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
• Subject is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
• Is either unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption.

Lab values

• Has a history or current evidence of any condition, therapy, or laboratory abnormality.

Other

• Is pregnant or breastfeeding, or expecting to conceive or father children.
• Is, in the judgement of the investigator, unlikely to comply with the study procedures, restrictions, and requirements of the study.

• Male/female subjects who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of invasive breast cancer
• Have histologically confirmed TNBC, as defined by the most recent ASCO/CAP guidelines.
• Confirmed germline BRCA 1/2 mutated.
• Have previously untreated locally advanced non-metastatic (M0) TNBC defined as the following combined primary tumor (T) and regional lymph node (N) staging per AJCC for breast cancer staging criteria version 7 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
• It has been confirmed that there is no distant metastasis to each organ by the following tests. Chest: Contrast CT or FDG-PET/CT Abdominal: Contract CT\* or FDG-PET/CT Bone: Bone scintigraphy or FDG-PET/CT Brain: In the case of no central nervous system symptoms, examination for brain metastasis is not required.
• The subject (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Have adequate organ function as defined in the protocol. Specimens must be collected within 10 days prior to the start of study treatment.