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 thesubject 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 pointduring 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 tostudy drug administration. There is no limit on the number of prior therapies. ForER/PR-positive tumors, endocrine therapy must have been included in at least one ofthose prior regimens. Prior capecitabine is allowed only if not given in thetreatment 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 positivityrate 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 thana complete pCR, defined as the absence of residual invasive cancer in resectedbreast specimen and sampled lymph nodes with residual noninvasive cancer or in situdisease allowed. (Phase II and Parallel Baseline Arm only)

• H. Must not have received prior systemic treatment for breast cancer except forthose included in the neoadjuvant regimen and the neoadjuvant regimen must not haveincluded 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 methodof contraception to avoid pregnancy throughout the study and for at least 24 weeksafter the last dose of study drug to minimize the risk of pregnancy. Prior to studyenrollment, women of childbearing potential must be advised of the importance ofavoiding pregnancy during trial participation and the potential risk factors for anunintentional pregnancy.

• L. Males with female partners of child-bearing potential must agree to usephysician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy)throughout the study and should avoid conceiving children for 24 weeks following thelast dose of study drug.

Exclusion Criteria:

• A. Females or males of childbearing potential who are unwilling or unable to use anacceptable method to avoid pregnancy for the entire study period and for at least 24weeks after the last dose of study drug.

• B. Females who are pregnant or breastfeeding.

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

• D. Hepatitis B infection except for prior vaccination. (Phase I and Phase II only).

• E. Known history of tuberculosis injection. (Phase I and Phase II only).

• F. A history of diverticulitis. (Phase I and Phase II only).

• G. Use of live vaccines within 30 days prior to study treatment due to the risk ofinfection. 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 forinjection are generally killed virus vaccines and are allowed; however, intranasalinfluenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed. (Phase I and Phase II only)

• H. History of other malignancy that in the primary oncologist's estimation has atthe time of study participation a higher risk of recurrence or death than thestudy-related cancer.

• I. Prisoners or subjects who are involuntarily incarcerated.

• J. Subjects who are compulsorily detained for treatment of either a psychiatric orphysical illness.

• K. Subjects demonstrating an inability to comply with the study and/or follow-upprocedures.