The goal of this clinical research study is to learn if receiving atezolizumab and abraxane
(nab-paclitaxel) in combination before surgery and atezolizumab alone after surgery can help
to control breast cancer. The safety of this study drug combination will also be studied.
This is an investigational study. Atezolizumab is not FDA approved or commercially available.
It is currently being used for research purposes only. Nab-paclitaxel is FDA approved and
commercially available for the treatment of metastatic (has spread) breast cancer. The study
doctor can explain how the study drug combination is designed to work.
Up to 37 participants will be enrolled in this study. All will take part at MD Anderson.
Study Drug Administration:
Each study cycle is 21 days. You will receive the study drugs in 2 sets of 4 cycles (4 cycles
before surgery and 4 cycles after surgery).
On Day 1 of Cycle 1, you will receive atezolizumab by vein over about 60 minutes.
On Day 1 of each later cycle before and after surgery, if you tolerated the first infusion,
you will receive future infusions of atezolizumab by vein over 30 minutes.
You will receive nab-paclitaxel by vein over about 30 minutes on Days 1, 8, and 15 of Cycles
1-4 before surgery.
If you have side effects, the study doctor may decide to lower your dose of study drugs or
have you stop taking the drugs. You may be able to restart the study drug later at the same
or a lower dose. The study doctor will discuss this with you.
On Day 1 of all cycles:
- You will have a physical exam.
- Blood (about 2 tablespoons) will be drawn for routine tests.
- During Cycle 3, you will have an ultrasound of your breast(s) before surgery. Additional
imaging may be done as part of your routine care, if the doctor thinks it is needed.
- During Cycle 3, blood (about 1 tablespoon each time) will be drawn before surgery and at
the time of surgery.
On Days 8 & 15 of Cycles 1-4, blood (about 2 tablespoons) will be drawn for routine testing.
Within 6 weeks after you have received 4 cycles of study drugs, you will have surgery as part
of your standard of care and part of the tumor tissue that is removed during surgery will be
collected for biomarker testing. You will be given a surgery consent form that describes the
procedure and its risks.
On Day 21 of Cycle 8, blood (about 1 tablespoon) will be drawn for routine and biomarker
Additional Research Testing:
If there is any tumor tissue left over after study procedures, part of this tumor tissue will
be sent to the sponsor (Genentech) for further biomarker and immune system testing. Before
your samples are sent to the sponsor for banking, your name and any personal identifying
information will be coded to protect your privacy. The sponsor will not have access to the
codes that link the samples to your identity. MD Anderson will not have oversight of any
leftover samples that will be banked by the sponsor for additional research. The tissue
samples sent to the sponsor for this additional research will be used up during this planned
Length of Treatment:
You may receive the study drugs for about 4 cycles before your surgery and about 4 cycles
after your surgery (8 cycles total). You will no longer be able to take the study drug, if
intolerable side effects occur, or if you are unable to follow study directions. You may be
able to continue taking the study drugs if the disease gets worse if the doctor thinks it is
in your best interest.
Your participation on the study will be over after follow-up.
Every 6 months for up to 3 years, you will either have a clinic visit or you will be called
by a member of the study staff and asked how you are doing. If you are called, each call
should last about 15-20 minutes.
1. Signed written informed consent
2. Histologically confirmed primary invasive adenocarcinoma of the breast with the size
of the primary tumor being at least 1.5 cm, or at least 1 biopsy confirmed involved
lymph node >1.5 cm, on imaging by either mammography, ultrasound or breast MRI.
3. ER and PR expression both <10% by immunohistochemistry (IHC) and HER2 negative or
non-amplified as determined by the current ASCO-CAP criteria which are as follows:
HER2 testing by IHC as 0 or 1+. If HER2 is 2+, ISH (in situ hybridization) must be
performed. HER2 is positive for gene amplification if: IHC 3+ based on circumferential
membrane staining that is complete, intense, ISH positive based on: Single-probe
average HER2 copy number >/= 6.0 signals/cell. Dual-probe HER2/CEP17 ratio >/= 2.0;c,e
with an average HER2 copy number >/=4.0 signals/cell Dual-probe HER2/CEP17 ratio >/=
2.0;c,e with an average HER2 copy number <4.0 signals/cell Dual-probe HER2/CEP17 ratio
< 2.0;c,e with an average HER2 copy number >/= 6.0 signals/cell
4. No prior treatment for primary invasive adenocarcinoma of the breast such as
irradiation, chemotherapy, hormonal therapy, immunotherapy, investigational therapy or
surgery other than the anthracycline and cyclophosphamide chemotherapy with or without
5-fluorouracil given as part of participation in protocol 2014-0185. Treatment for
ductal carcinoma in situ is allowed, such as surgery, hormonal therapy and
5. ECOG performance status of 0-1
6. Baseline MUGA or echocardiogram scans with LVEF of > 50%
7. Patient must have adequate organ function as determined by the following laboratory
values: ANC >/= 1500 cells/uL, WBC counts > 2500/uL, Lymphocyte count >/= 300/uL,
Platelet count >/=100,000/uL; Hemoglobin >/= 9.0 g/dL, Total bilirubin </= 1.5 x upper
limit of normal (ULN) with the following exception: Patients with known Gilbert
disease who have serum bilirubin level </= 3 x ULN may be enrolled. AST and ALT </=
3.0 x ULN, Alkaline phosphatase </= 2.5 x ULN
8. Continued from #7: Serum creatinine </= 1.5 x ULN or creatinine clearance >/= 50
mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation: (140
- age) x (weight in kg) x (0.85 if female)/ 72 x (serum creatinine in mg/dL), INR and
aPTT </= 1.5 x ULN. 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
9. Men or women 18 years of age or older
10. Women of childbearing potential must be using an adequate method of contraception to
avoid pregnancy throughout the study and for up to 6 months after the last dose of
investigational product in such a manner that the risk of pregnancy is minimized. Men
on study and for at least 6 months after the last dose of nab-paclitaxel also must be
using contraception. Women of childbearing potential (WOCBP) are women who have not
been postmenopausal greater than 1 year or undergone a hysterectomy and/or bilateral
11. Negative serum or urine pregnancy test for women within 72 hours of receiving the
first dose of the study medication for women of childbearing potential
12. Participated on protocol 2014-0185 TNBC Neoadjuvant Triaging protocol and classified
as having insufficient tumor shrinkage by imaging (<80% shrinkage after 4 cycles of
anthracycline-based chemotherapy based upon diagnostic imaging).
1. Women who are pregnant or breast-feeding
2. Known metastatic disease
3. Disease free of prior malignancy for < 5 years with the exception of curatively
treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, or
transitional cell carcinoma.
4. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
or checkpoint pathways)
5. Has had major surgery within 21 days before Cycle 1, Day 1
6. Uncontrolled inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
7. Myocardial infarction within 6 months before starting therapy, symptomatic congestive
heart failure (New York Heart Association > class II), unstable angina, or unstable
cardiac arrhythmia requiring medication
8. Serious intercurrent infections or non-malignant medical illness that are uncontrolled
or the control of which may be jeopardized by this therapy
9. Psychiatric disorders or other conditions rendering the subject incapable of complying
with the requirements of the protocols
10. History or risk of autoimmune disease, including but not limited to systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, 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 be eligible
11. Continued from #9: 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 ocular manifestations 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%, fluocinolone 0.01%, desonide
0.05%, alclometasone 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 oral steroids)
12. Known to be human immunodeficiency virus positive
13. Patients with prior allogeneic stem cell or solid organ transplantation
14. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan.
History of radiation pneumonitis in the radiation field (fibrosis) is permitted
15. Patients with active hepatitis B (defined as having a positive hepatitis B surface
antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B
virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg
test and a positive antibody to hepatitis B core antigen [anti HBc] antibody test) are
eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction is negative for HCV RNA
16. Active tuberculosis
17. Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or
anticipation that such a live, attenuated vaccine will be required during the study.
Influenza vaccination should be given during influenza season only (approximately
October to March). Patients must not receive live, attenuated influenza vaccine (e.g.,
FluMist) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study
18. Treatment with systemic immunostimulatory agents (including but not limited to
interferons or IL-2) within 4 weeks or five half-lives of the drug, whichever is
19. Treatment with systemic corticosteroids or other systemic immunosuppressive
medications (including but not limited to prednisone, dexamethasone, cyclophosphamide,
azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents),
or anticipated requirement for systemic immunosuppressive medications during the
trial. Patients who have received acute, low dose, systemic immunosuppressant
medications (e.g., dexamethasone prior to the anthracycline-based chemotherapy for
nausea) may be enrolled in the study. The use of inhaled corticosteroids and
mineralocorticoids (e.g., fludrocortisone) is allowed
20. Concurrent disease or condition that would interfere with study participation or
safety, such as any of the following: Active, clinically significant infection either
grade > 2 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse
Events (CTCAE) v4.03 or requiring the use of parenteral anti-microbial agents within
14 days before Day 1 of study drug, Clinically significant bleeding diathesis or
coagulopathy, including known platelet function disorders, Non-healing wound, ulcer,
or bone fracture
21. Known hypersensitivity to any of the components of atezolizumab or nab-paclitaxel
22. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins