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)

Prior treatment

• A. Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 24 weeks after the last dose of study drug.
• D. Hepatitis B infection except for prior vaccination. (Phase I and Phase II only).
• G. Use of live vaccines within 30 days prior to study treatment due to the risk of infection. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella (MMR), varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed. (Phase I and Phase II only)

Other illness

• E. Known history of tuberculosis injection. (Phase I and Phase II only).
• F. A history of diverticulitis. (Phase I and Phase II only).
• H. History of other malignancy that in the primary oncologist's estimation has at the time of study participation a higher risk of recurrence or death than the study-related cancer.
• J. Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.

Lab values

• C. History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician.

Other

• B. Females who are pregnant or breastfeeding.
• I. Prisoners or subjects who are involuntarily incarcerated.
• K. Subjects demonstrating an inability to comply with the study and/or follow-up procedures.

• 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:
  • Absolute neutrophil count (ANC) \> 1500/mcl (use of G-CSF is allowed)
  • Platelets ≥ 100,000/mcl
  • Hemoglobin ≥ 9 (pRBC +/- ESA are allowed)
  • ALT ≤ 5 x ULN
  • AST ≤ 5 x ULN
  • Bilirubin ≤ 3 x ULN
  • 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.