- Histologically or cytologically confirmed newly diagnosed ER-/HER2- breast cancer. ER
and PR < Allred score of 3 or < 1% positive staining cells in the invasive component
of the tumor. HER2 negative by FISH or IHC staining 0 or 1+ according to NCCN
- Clinical stage II or III (by AJCC 8th edition at least T2, any N, M0 or if N+ then any
T) breast cancer eligible for neoadjuvant chemotherapy with complete surgical excision
of the breast cancer after neoadjuvant therapy as the treatment goal.
- No prior therapy for this disease
- At least 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- Normal bone marrow and organ function as defined below:
- Leukocytes ≥ 2,000/mcL (stable off any growth factor within 4 weeks of first
study treatment administration)
- Absolute neutrophil count ≥ 1,500/mcL (stable off any growth factor within 4
weeks of first study treatment administration)
- Platelets ≥ 100,000/mcL (stable off any growth factor within 4 weeks of first
study treatment administration)
- Hemoglobin ≥8.5 g/dl (transfusion to achieve this level is not permitted within 2
weeks of first study treatment administration)
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN) (except
participants with Gilbert's Syndrome who must have normal direct bilirubin)
- AST(SGOT)/ALT(SGPT) ≤ 2.0 x IULN
- Alkaline phosphatase <2.5 x ULN
- Serum creatinine < 1.5 x ULN or creatinine clearance > 40 mL/min by
- Albumin ≥ 3 g/dL
- INR and aPTT <1.5 x IULN (This applies only to patients who do not receive
therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such
as low-molecular-weight heparin or warfarin, should be on a stable dose).
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to
the start of study treatment.
- Women must not be breastfeeding.
- WOCBP must agree to follow instructions for method(s) of contraception for the
duration of treatment with study treatment(s) and for a total of 10 months
- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).
- Consent for fresh pre-treatment, on-treatment, biopsy samples at acceptable clinical
risk, as judged by the investigator.
- Participants must be willing and able to comply with scheduled visits, treatment
schedule, and laboratory testing
- Prior treatment with immunotherapy for cancer
- Known metastatic disease
- Known invasive cancer in contralateral breast
- Patients with a previous history of non-breast malignancy are eligible only if they
meet the following criteria for a cancer survivor:
- Has undergone potentially curative therapy for all prior malignancies AND
- Has been considered disease-free for at least 1 year (with the exception of basal
cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix.
- Currently receiving any other investigational agents.
- Concomitant use of statins while on study (there is a 14-day washout). However, a
participant using statins for over 3 months prior to study drug administration and in
stable status without CK rise may be permitted to enroll.
- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to paclitaxel, carboplatin, nivolumab, cabiralizumab, or other
agents used in the study. Known history of sensitivity to infusions containing Tween
20 (polysorbate 20) and Tween 80 (polysorbate 80).
- Evidence of uncontrolled ongoing or active infection, requiring parenteral
anti-bacterial, anti-viral, or anti-fungal therapy ≤ 7 days prior to administration of
study treatment. Patients receiving prophylactic antibiotics (e.g., for prevention of
a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
- Patients with prior allogeneic bone marrow transplantation or prior solid organ
- History or risk of autoimmune disease, including, but not limited to, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease (Crohn's disease and
ulcerative colitis), vascular thrombosis associated with antiphospholipid syndrome,
Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome,
multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis.
- Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid
replacement hormone may be eligible.
- Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may
- Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis would
be excluded) are permitted provided that they meet the following conditions:
- Patients with psoriasis must have a baseline ophthalmologic exam to rule out
- Rash must cover less than 10% of body surface area (BSA)
- Disease is well controlled at baseline and only requiring low potency
topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%,
flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
- No acute exacerbations of underlying condition within the last 12 months
(not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate,
retinoids, biologic agents, oral calcineurin inhibitors; high potency or
- History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
pneumonia, etc.), or evidence of active pneumonitis on screening chest computed
tomography (CT) scan.
- Current or history of clinically significant muscle disorders (e.g., myositis), recent
unresolved muscle injury, or any condition known to elevate serum CK levels.
- Uncontrolled or significant cardiovascular disease
- History of any chronic hepatitis as evidenced by the following:
- Positive test for hepatitis B surface antigen
- Positive test for qualitative hepatitis C viral load (by polymerase chain
- Positive test for latent tuberculosis (TB) at screening (e.g. T-SPOT or Quantiferon
test) or evidence of active TB.
- Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of
need for a major surgical procedure during the course of the study with the exception
of the planned breast cancer surgery that is part of the trial design. Participants
must have recovered from the effects of major surgery or significant traumatic injury
at least 14 days before the first dose of study treatment.
- Any uncontrolled medical condition which, in the opinion of the Investigator, would
pose a risk to participant safety or interfere with study participation or
interpretation of individual participant results.
- Treatment with systemic immunosuppressive medications (including, but not limited to,
prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor
necrosis factor [anti-TNF] agents) within 2 weeks prior to Cycle 1, Day 1.
- Patients who have received acute, low dose, systemic immunosuppressant
medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled.
- The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone)
for patients with orthostatic hypotension or adrenocortical insufficiency is
allowed. The use of replacement doses of prednisone or other corticosteroid for
adrenocortical insufficiency is allowed
- Participants with a condition requiring systemic treatment with either
corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive
medications within 14 days of start of study treatment. Inhaled or topical
steroids and adrenal replacement steroid doses > 10 mg daily prednisone
equivalent are permitted in the absence of active autoimmune disease.
- Evidence of coagulopathy or bleeding diathesis.
- Ascites needing paracentesis or medical management.
- Patients positive for human immunodeficiency virus (HIV) are NOT excluded from this
study, but HIV-positive patients must have:
- A stable regimen of highly active anti-retroviral therapy (HAART)
- No requirement for concurrent antibiotics or antifungal agents for the prevention
of opportunistic infections
- A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard