Open-label, Single Center, Single-arm, Phase 2 Study of Neoadjuvant Pembrolizumab in Combination With Carboplatin and Paclitaxel in Patients With Stage 1 cT1b-T1cN0M0 Triple Negative Breast Cancer

Participants are eligible to be included in the study only if all of the following criteria apply:

2. AJCC 8 anatomic tumor Stage 1 T1b-T1c, N0, M0. All participants with clinically suspicious nodes must undergo core or fine needle biopsy per standard clinical practice to pathologically assess at least 1 suspicious index node. Participants with suspicious nodes that are biopsy negative will be eligible.

3. Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of Stage 1 T1b-T1cN0M0 TNBC will be enrolled in this study.

4. Male participants: A male participant must agree to use a contraception as detailed in Appendix 2 of this protocol during the treatment period and for at least 120 days, corresponding to time needed to eliminate any study treatment(s) (e.g. 5 terminal half-lives for pembrolizumab and/or any active comparator/combination) plus an additional 90 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose after the last dose of study treatment and refrain from donating sperm during this period.

5. Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 2), not breastfeeding, and at least one of the following conditions applies:

1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 OR

2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during the treatment period and for at least 120 days (corresponding to time needed to eliminate any study treatment(s) (pembrolizumab and/or any active comparator/combination) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity after the last dose of study treatment.

6. Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible.

7. The participant provides written informed consent for the trial.

8. Archival tumor tissue sample or newly obtained \[core, incisional or excisional\] biopsy of a tumor lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.

9. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (appendix 3). Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.

10. Have adequate organ function as defined in the following table (Table 3). Specimens must be collected within 10 days prior to the start of study intervention.

11. Non-English speaking participant can enroll in the study as long as they speak a language for which interpretation can be provided by a licensed interpreter either in person or virtually.

12. Criteria for known HIV positive participants.

2. HIV screening tests are not required unless:

i. Known history of HIV ii. As mandated by local health authority

13. Criteria for known Hepatitis B and C positive participants Hepatitis B and C screening tests are not required unless:

* Known history of HBV or HCV infection

* As mandated by local health authority 13.1 Hepatitis B positive Participants

* Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.

Table 3 Adequate Organ Function Laboratory Values System Laboratory Value Hematological Absolute neutrophil count (ANC) = ≥1500/µL Platelets = ≥100 000/µL Hemoglobin = ≥9.0 g/dL or ≥5.6 mmol/La Renal Creatinine OR Measured or calculatedb creatinine clearance (GFR can also be used in place of creatinine or CrCl) = ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN Hepatic Total bilirubin = ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN AST (SGOT) and ALT (SGPT) = ≤2.5 × ULN (≤5 × ULN for participants with liver metastases) Coagulation International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) = ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal. a Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks. b Creatinine clearance (CrCl) should be calculated per institutional standard. Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.

What this study is about