Sarilumab plus Capecitabine for the Treatment of HER2 Negative Metastatic Breast Cancer and Stage I-III Triple Negative Breast Cancer with High-Risk Residual Disease, the EMPOWER Trial

Inclusion Criteria

• Written informed consent obtained from the subject and the ability for the subject to comply with all the study-related procedures
• Both males and females ≥ eighteen years of age
• PHASE I ONLY: 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 estrogen receptor (ER)/ progesterone receptor (PR) immunohistochemistry (IHC) positivity rate of < 10% and Her2/neu-negative
• A life expectancy of at least six months
• PHASE I ONLY: Any previous cytotoxic chemotherapy must have been a minimum of three 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
• PHASE II AND PARALLEL BASELINE ARM ONLY: 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: A pathologic confirmation of stage I, or II, or III TNBC with less than a pathologic complete response (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: 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
• ECOG performance status ≤ 2
• Absolute neutrophil count (ANC) ≥ 1500/mcl (use of granulocyte colony-stimulating factor [G-CSF] is allowed as long as the patient is able to maintain ANC ≥ 1500/mcl for 14 days or greater without G-CSF prior to enrollment)
• Platelets ≥ 100,000/mcl
• Hemoglobin ≥ 8; transfusion to meet eligibility criteria is allowed as long as the patient is able to maintain a hemoglobin (Hgb) ≥ 8 for 7 days or greater without transfusion prior to enrollment
• Alanine aminotransferase (ALT) ≤ 5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 5 x ULN
• Bilirubin ≤ 3 x ULN (unless patient has known Gilbert’s disease in which case a total bilirubin ≤ 5 x ULN is allowed)
• Glomerular filtration rate (GFR) ≥ 30 ml/min
• 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. WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not post-menopausal. Post-menopause is defined as: * No menses for one year in the absence of prior chemotherapy or tamoxifen use, or no menses after surgical removal of all ovarian tissue, * In female survivors with prior chemotherapy or pelvic radiation exposure or survivors on tamoxifen, serial estradiol levels may be useful to confirm post-menopausal status * For peri- or pre- menopausal female survivors who have become amenorrheic and later develop bleeding, serial estradiol levels can be useful to determine return of ovarian function. Other markers including follicle-stimulating hormone (FSH), anti-Mullerian hormone (AMH), and inhibin may provide additional information on ovarian status in female cancer survivors with prior chemotherapy or those on tamoxifen, but alone are not reliable to ensure menopausal status
• 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

Exclusion Criteria

• 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
• Females who are pregnant or breastfeeding
• 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
• PHASE I AND PHASE II ONLY: Hepatitis B infection, except for prior vaccination
• PHASE I AND PHASE II ONLY: Known history of tuberculosis infection
• PHASE I AND PHASE II ONLY: A history of diverticulitis
• PHASE I AND PHASE II ONLY: 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
• 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
• Prisoners or subjects who are involuntarily incarcerated
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness
• Subjects demonstrating an inability to comply with the study and/or follow-up procedures