This study will advance a novel and potent strategy to eliminate minimal residual disease
(MRD) in triple negative breast cancer (TNBC) present even after multimodal treatment,
thereby improving survival and increasing cure rate in this aggressive cancer. Patients with
locally advanced TNBC are at high risk of developing lethal metastatic disease within 2 years
of diagnosis, especially for those without a pathologic complete response (pCR) after
neoadjuvant chemotherapy. The high risk occurs despite surgical excision of the primary tumor
and axillary lymph nodes to eliminate residual disease.
The study will consist of two phases, I and II. Phase I will be made up of 2 patient cohorts,
Cohorts A and B.
- Cohort A, will include Stage I to III TNBC patients with less than a complete pCR after
neoadjuvant therapy who will be treated with capecitabine (1000mg/m2/BID; for 14 days
every 21 days) as standard of care. This cohort will be used to determine baseline bone
marrow disseminated tumor cells (BM DTC) response to capecitabine alone.
- Cohort B, will include patients with metastatic TNBC, HER2/neu-negative and hormone
resistant breast cancer. A total of 4 doses of sarilumab will be given with the starting
dose of 150 mg SQ at 3-weeks cycles given 3 days prior to each of the first 4 of 8
cycles of capecitabine (1000 mg/m2/BID; for 14 days every 21 days). If dose escalation
is possible, sarilumab will be administered every 3 weeks at 200 mg SQ for 4 doses.
Phase II is a single arm study in Stage I to III TNBC with less than a complete pCR after
neoadjuvant therapy evaluating the combination of sarilumab with capecitabine (1000mg/m2/BID;
for 14 days every 21 days) as compared to historical control patients treated with
capecitabine alone. There are 8 cycles of capecitabine. The first 4 cycles will be combined
with sarilumab. The Phase II sarilumab dose will be determined by the Phase I best tolerated
dose. In patients without bone marrow DTC clearance after 4 doses of sarilumab, 4 more doses
of sarilumab will be given in combination with the last 4 cycles of capecitabine.
- 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 Cohort B 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 Cohort B only)
- F. A diagnosis of TNBC confirmed histologically and defined as ER/PR IHC positivity
rate of <10% and Her2/neu-negative. (Phase I Cohort A and Phase II 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 I Cohort A and Phase II 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 I Cohort A and Phase II 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
- 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.
- 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.
- B. Females who are pregnant or breastfeeding.
- 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.
- D. Hepatitis B infection except for prior vaccination. (Phase I Cohort B and Phase II
- E. Known history of tuberculosis injection. (Phase I Cohort B and Phase II only).
- F. A history of diverticulitis. (Phase I Cohort B 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 Cohort B 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
- I. Prisoners or subjects who are involuntarily incarcerated.
- J. Subjects who are compulsorily detained for treatment of either a psychiatric or
- K. Subjects demonstrating an inability to comply with the study and/or follow-up