Personalizing the Use of Pembrolizumab for Patients Who Have a Strong Response in Early Triple Negative Breast Cancer

Inclusion criteria

• 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;
• Age ≥ 18 years;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
• 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;
• 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;
• Patients previously treated with neoadjuvant chemotherapy in combination with pembrolizumab for a minimum of 6 cycles (All systemic chemotherapy must have been completed preoperatively);
• 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);
• Have had an adequately excised breast cancer (surgical removal of all clinically evident disease in the breast and lymph nodes) :
• 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.
• 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;
• Patients that have received adequate locoregional radiation therapy or with planned adequate locoregional radiation therapy;
• Adequate organ and bone marrow functions. All screening lab tests should be performed within 28 days before randomisation;
• Absolute Neutrophil Count (ANC) ≥ 1,000 /µL
• Platelets ≥ 100,000 /µL
• Hemoglobin ≥ 9 g/dL
• Creatinine clearance ≥ 30 mL/min for subject with creatinine levels \> 1.5 x institutional upper limit of normal (ULN)
• 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)
• Aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤ 2.5 x ULN
• 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;
• 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);
• 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;
• Patients should be able and willing to comply with study visits and procedures as per protocol;
• Patients must be affiliated to a Social Security System (or equivalent).

Exclusion criteria

• Radiological or clinical evidence of metastatic disease (stage IV) documented by imaging or clinical examination;
• Evidence of recurrent disease following preoperative therapy and surgery;
• Any prior history of (ipsi- or contralateral) invasive breast cancer;
• Patients with a prior or concurrent malignancy (other than invasive breast cancer) whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of the investigational regimen;
• Patients for whom pembrolizumab has been permanently discontinued during the neoadjuvant phase of treatment due to pembrolizumab-related AE;
• History of intolerance, including Grade 3 or 4 infusion reaction or hypersensitivity to pembrolizumab or murine proteins or any component of the product;
• Medical conditions that require chronic systemic steroids (\> 10 mg prednisone or equivalent) or any other form of immunosuppressive medication in the past 2 years. Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment;
• Known active liver disease, e.g. due to HBV, HCV, autoimmune hepatic disorders, or sclerosing cholangitis;
• HIV-infected patients on effective anti-retroviral therapy with detectable viral load within 6 months prior to enrollment;
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better;
• Patients unwilling or unable to comply with the medical follow-up required by the trial due to geographic, familial, social, or psychological reasons;
• Persons deprived of their liberty or under protective custody or guardianship;
• Participation in another therapeutic trial within the 30 days prior to randomisation.