Neoadjuvant Pembrolizumab and Carboplatin Plus Paclitaxel for Stage I Triple-negative Breast Cancer

This is a single arm, proof of concept phase II clinical trial to evaluate the combination of Pembrolizumab and Carboplatin plus Paclitaxel in patients with localized TNBC (tumor size ≥ 10 mm and ≤ 20 mm by mammogram and/or ultrasound, and/or ≥ 10 mm and ≤ 25 mm by breast MRI if performed within 2 weeks after biopsy, considering possible tissue inflammation post-procedure, as per local assessment), node-negative status (by clinical exam and local radiological evaluation) and who have not previously received chemotherapy, targeted therapy, and/or radiotherapy for invasive breast cancer.

Inclusion Criteria: 1. Written informed consent form (ICF) prior to beginning specific protocol procedures. 2. Female or male patients ≥ 18 years of age. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 4. Histologically confirmed TNBC as defined by the most ASCO/CAP guidelines based on local laboratory results. Note: TNBC means tumors that have \ 3.0 x 10 9/L, absolute neutrophil count (ANC) ≥ 1.5 x 10 9/L, platelet count ≥ 100.0 x10 9/L, and hemoglobin ≥ 9.0 g/dL (≥ 5.6 mmol/L). * Hepatic: total bilirubin ≤ institutional upper limit of normal (ULN) (except for Gilbert's syndrome); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 times ULN. * Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. 15. Patient must be accessible for treatment and follow-up. Exclusion Criteria: 1. 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). 2. Has received prior systemic anti-breast cancer therapy, including an investigational agents or has used an investigational device within 4 weeks prior to allocation. 3. Has received prior taxane or platinum-based therapy. 4. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 5. Has had an allogenic tissue/solid organ transplant. 6. Has a history of invasive malignancy within the last 5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. For other cancers considered to have a low risk of recurrence, discussion with the Medical Monitor is required. 7. Participation in an interventional clinical study within 4 weeks of first dose of study treatment. 8. Major surgical procedure or significant traumatic injury within 14 days prior to enrolment or anticipation of need for major surgery within the course of the study treatment. 9. Has received a live vaccine within 30 days of first dose of study treatment. 10. Active autoimmune disease that has required systemic treatment in past 2 years, or ANY diagnosis of immunodeficiency or is receiving systemic steroid therapy (e.g, dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. Replacement therapy (e.g, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. 11. Current known infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antigen \[HBsAg\] test and a positive hepatitis B core antibody \[HBcAb\] test, accompanied by a negative HBV DNA test) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. 12. Other active uncontrolled infection at the time of enrollment. 13. Significant cardiovascular disease within the last 6 months OR congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA Class III or IV. 14. History of (non-infectious) pneumonitis that required steroids or current pneumonitis. 15. Other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation. 16. Pregnancy or breastfeeding or expecting to conceive children within the projected duration of the trial, starting with the screening visit through 6 months after the last dose of trial treatment. 17. Known hypersensitivity to the components of the study or its analogs.