OPT-PEMBRO: Testing whether people with early-stage triple-negative breast cancer who have no remaining cancer after chemotherapy, pembrolizumab and surgery can safely stop immunotherapy after surgeryOPTimizing Adjuvant Prescription of PEMBROlizumab in Patients With Early-stage Triple-negative Breast Cancer Achieving Pathologic Complete Response After Standard Neoadjuvant Chemotherapy and Pembrolizumab

Inclusion

1. Patient must have signed a written informed consent prior to any trial-related procedures. When the patient is physically unable to give his written consent, a trusted person of his choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent;
2. Age ≥ 18 years;
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
4. Histologically documented stage II-III breast cancer according to the primary tumour-regional lymph node anatomic staging criteria of the American Joint Committee on Cancer (AJCC), 8th edition as determined by the investigator during radiologic assessment, clinical assessment or both;
5. Estrogen receptor (ER) and Progesterone receptor (PR) ≤10%; HER2-negative as per ASCO/CAP guidelines Note: In case of bilateral breast cancer, participation in the study is permitted as long as both tumours are triple negative;
6. Patients previously treated with neoadjuvant chemotherapy in combination with pembrolizumab for a minimum of 6 cycles (All systemic chemotherapy must have been completed preoperatively);
7. Absence of residual invasive disease in the breast or lymph nodes after the completion of neoadjuvant therapy (Residual ductal carcinoma in situ [DCIS] is allowed);

8. Have had an adequately excised breast cancer (surgical removal of all clinically evident disease in the breast and lymph nodes) :

   1. Breast surgery: patients must have undergone either breast-conserving surgery or total mastectomy with histologically negative margins for invasive tumour and DCIS. Patients with margins positive for lobular carcinoma in situ (LCIS) are eligible without additional resection.
   2. Lymph node surgery: patients must have had sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND) to evaluate the pathologic nodal status;
9. Patients that have received adequate locoregional radiation therapy or with planned adequate locoregional radiation therapy;

10. Adequate organ and bone marrow functions. All screening lab tests should be performed within 28 days before randomisation;

    1. Absolute Neutrophil Count (ANC) ≥ 1,000 /µL
    2. Platelets ≥ 100,000 /µL
    3. Hemoglobin ≥ 9 g/dL
    4. Creatinine clearance ≥ 30 mL/min for subject with creatinine levels > 1.5 x institutional upper limit of normal (ULN)
    5. Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN (Patients with Gilbert's disease with a total bilirubin ≤ 2.5 x ULN and direct bilirubin within normal limits are permitted)
    6. Aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤ 2.5 x ULN
11. Randomisation must take place no more than 12 weeks after breast surgery. Adjuvant radiotherapy is authorized. If given, as per investigator discretion it can be given concurrently with pembrolizumab;
12. Patients must not be pregnant or nursing (for women of childbearing potential only, a negative serum pregnancy test must be obtained within 7 days of Cycle 1 Day 1);
13. Women of childbearing potential and male patients must agree to use 1 effective form of contraception and up to 4 months after the last dose of study drugs;
14. Patients should be able and willing to comply with study visits and procedures as per protocol;
15. Patients must be affiliated to a Social Security System (or equivalent).