Safety and Blood Immune Cell Study of Anakinra Plus Physician's Chemotherapy Choice in Metastatic Breast Cancer Patients

In an attempt to reverse the immune suppressive microenvironment and to enhance chemotherapy
effectiveness, decrease tumor metagenicity and decrease IL-1-induced fatigue, metastatic
breast cancer (MBC) patients will be treated with chemotherapy plus anakinra. This is a
pilot safety, single arm, open label trial. The objective is to determine the safety of
anakinra plus the physician's chemotherapy choice (TPC) of nab paclitaxel, capecitabine,
eribulin, or vinorelbine in patients with MBC and to define an anakinra-induced anti-IL-1
whole blood transcriptional profile.

Inclusion Criteria:

- Female or male patients ≥18 years of age.

- Histologically confirmed invasive breast cancer, locally unresectable or metastatic.

- No more than 4 prior chemotherapy regimens for metastatic disease.

- Patients currently being treated with nab paclitaxel, capecitabine,eribulin, or
vinorelbine who have had a CR, PR, or SD and who have developed Grade 2, 3, or 4
fatigue on the chemotherapy are eligible for the study. It should be anticipated that
these patients will continue to be treated on the same chemotherapy agent for at
least 3 more months beyond the time of enrollment.

- Prior hormonal therapy in the adjuvant or metastatic setting is permitted.

- HER2-negative breast cancer. If HER2-, it is defined as follows:

1. FISH-negative (FISH ratio <2.0), or

2. IHC 0-1+, or

3. IHC 2+ AND FISH-negative (FISH ratio<2.0)

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

- Adequate hematologic function, defined by:

1. Absolute neutrophil count (ANC) >1500/mm^3

2. Platelet count ≥100,000/mm^3

3. Hemoglobin >8 g/dL

- Adequate liver function, defined by:

1. AST and ALT ≤2.5 x the upper limit of normal (ULN) or ≤5 x ULN in presence of
liver metastases

2. Total bilirubin ≤1.5 x ULN

- Adequate renal function, defined by:

a. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance of ≥40 ml/min

- Measurable or nonmeasurable disease by RECIST v1.1 criteria

- Life expectancy ≥24 weeks

- Adequate recovery from recent surgery

1. Major surgical procedure >28 days from study entry

2. Minor surgical procedure >7 days from study entry (Portacath placement accepted
- patients can start treatment <7 days after portacath placement.)

- Patients with previous history of invasive cancers (including breast cancer) are
eligible if definitive treatment was completed more than 5 years prior to initiating
current study treatment, and there is no evidence of recurrent disease.

- Patient must be accessible for treatment and follow-up.

- All patients must be able to understand the investigational nature of the study and
give written informed consent prior to study entry

Exclusion Criteria:

- Patients with active or untreated brain metastases or meningeal metastases are
ineligible. Patients who have had brain metastases resected, or have received brain
radiation therapy >4 weeks prior to study entry are eligible if they meet all of the
following criteria: 1) patient has been off dexamethasone for >2 weeks; 2) no known
progression of brain metastasis.

- Previous radiotherapy for metastatic disease completed <2 weeks prior to study
treatment initiation.

- Women who are pregnant or lactating. All patients with reproductive potential must
agree to use effective contraception from time of study entry until at least 3 months
after the last administration of study drug.

- Patients who have any severe and/or uncontrolled medical conditions or other
conditions that could affect their participation such as: -

1. severe impaired lung functions as defined as spirometry and DLCO that is 50% of
the normal predicted value and/or O2 saturation that is 88% or less at rest on
room air

2. uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN

3. liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class
C).

- History of any other disease, physical examination finding, or clinical laboratory
finding giving reasonable suspicion of a disease or condition that contraindicates
use of an investigational drug, or that might affect interpretation of the results of
this study, or render the subject at high risk for treatment complications.

- Patients may not receive any other investigational treatments while participating in
this study.

- Patients receiving chronic, systemic treatment with corticosteroids or another
immunosuppressive agent. Topical or inhaled corticosteroids are allowed.

- Concurrent severe, uncontrolled infection or intercurrent illness including, but not
limited to, ongoing or active infection, or psychiatric illness/social situations
that would limit compliance with study requirements.