A Dose Finding Phase 1 of Sarilumab Plus Capecitabine in HER2/Neu-Negative Metastatic Breast Cancer and a Single-arm, Historically-controlled Phase 2 Study of Sarilumab Plus Capecitabine in Stage I-III Triple Negative Breast Cancer With High-Risk Residual Disease (EMPOWER)

Inclusion Criteria

• •A. Written informed consent obtained from the subject and the ability for the subject to comply with all the study-related procedures.
• •B. Both males and females ≥ eighteen years of age
• •C. A clinical diagnosis of metastatic triple negative or hormone resistant, Her2/neu-negative breast cancer that has been confirmed histologically at one point during the course of the disease. TNBC is defined as ER/PR IHC positivity rate of \<10% and Her2Neu-negative (Phase I only)
• •D. A life expectancy of at least 6 months. (Phase I only)
• •E. Any previous cytotoxic chemotherapy must have been a minimum of 3 weeks prior to study drug administration. There is no limit on the number of prior therapies. For ER/PR-positive tumors, endocrine therapy must have been included in at least one of those prior regimens. Prior capecitabine is allowed only if not given in the treatment regimen immediately prior to the enrollment in this study. (Phase I only)
• •F. A diagnosis of TNBC confirmed histologically and defined as ER/PR IHC positivity rate of \<10% and Her2/neu-negative. (Phase II and Parallel Baseline Arm only)
• •G. A pathologic confirmation of stage I, or II, or III breast cancer with less than a complete pCR, defined as the absence of residual invasive cancer in resected breast specimen and sampled lymph nodes with residual noninvasive cancer or in situ disease allowed. (Phase II and Parallel Baseline Arm only)
• •H. Must not have received prior systemic treatment for breast cancer except for those included in the neoadjuvant regimen and the neoadjuvant regimen must not have included capecitabine nor sarilumab. (Phase II and Parallel Baseline Arm only)
• •I. An ECOG Performance Status ≤2.
• •J. Adequate organ function defined as:
• •1. Absolute neutrophil count (ANC) \> 1500/mcl (use of G-CSF is allowed)
• •2. Platelets ≥ 100,000/mcl
• •3. Hemoglobin ≥ 9 (pRBC +/- ESA are allowed)
• •4. ALT ≤ 5 x ULN
• •5. AST ≤ 5 x ULN
• •6. Bilirubin ≤ 3 x ULN
• •7. GFR ≥ 30 ml/min
• •K. Women of childbearing potential (WOCBP) must be using a highly effective method of contraception to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug to minimize the risk of pregnancy. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
• •L. Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug.