Evaluating Anti-PD-L1 Antibody (Durvalumab) Plus Anti-CTLA-4 Antibody (Tremelimumab) in HR+/HER2- Breast Cancer

Inclusion Criteria:

1. Written informed consent and any locally-required authorization (e.g., HIPAA) obtained
from the subject prior to performing any protocol-related procedures, including
screening evaluations

2. Age >/= 18 years at time of study entry

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

4. Hormone receptor positive (defined as estrogen receptor [ER] and/or progesterone
receptor [PR] positive), HER2 negative breast cancer that is clinically staged II-III
with no known metastatic disease. ER and/or PR defined as positive if expression >10%
by immunohistochemistry (IHC). 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 if: IHC 3+
based on circumferential membrane staining that is complete, intense ISH positive
based on: 1)Single-probe average HER2 copy number >/= 6.0 signals/cell, 2) Dual-probe
HER2/CEP17 ratio >/= 2.0;c,e with an average HER2 copy number >/= 4.0 signals/cell, 3)
Dual-probe HER2/CEP17 ratio >/= 2.0;c,e with an average HER2 copy number <4.0
signals/cell, 4) Dual-probe HER2/CEP17 ratio < 2.0;c,e with an average HER2 copy
number >/= 6.0 signals/cell

5. Chemotherapy is planned for the patient in the neoadjuvant setting

6. Adequate normal organ and marrow function as defined below: 1) Hemoglobin >/=9.0 g/dL,
2) Absolute neutrophil count (ANC) >/=1.5 x 109/L (>/=1500 per mm3), 3) Platelet count
>/=100 x 109/L (>/=100,000 per mm3), 4) Serum bilirubin limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's
syndrome (persistent or recurrent hyperbilirubinemia that is predominantly
unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed
only upon treating physician, Principal Investigators (PI) or co-PIs approval. 5) AST
(SGOT)/ALT (SGPT) are present, in which case it must be 40 mL/min by the
Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for
determination of creatinine clearance.

7. Female subjects must either be of non-reproductive potential (i.e., post-menopausal by
history: >/= 60 years old and no menses for >/= 1 year without an alternative medical
cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history
of bilateral oophorectomy) or must have a negative urine pregnancy test upon study
entry.

8. Subject is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up.

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site)

2. Participation in another clinical study with an investigational product during the
last 1 month prior to initiation of therapy

3. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an
anti-CTLA4, including tremelimumab

4. History of another primary malignancy except for: 1) Malignancy treated with curative
intent and with no known active disease >/= 5 years before the first dose of study
drug and of low potential risk for recurrence, 2) Adequately treated non-melanoma skin
cancer or lentigo maligna without evidence of disease, 3) Adequately treated carcinoma
in situ without evidence of disease e.g., cervical cancer in situ

5. Has received therapy for this current diagnosis of breast cancer including endocrine
therapy or chemotherapy

6. A single QT interval corrected for heart rate (QTc) >/= 470 ms. If an ECG is
interpreted to be a prolonged QT interval, 2 additional ECGs will be obtained and the
PI will then evaluate all three ECGs and determine whether the patient should be
excluded. Mean QT interval corrected for heart rate (QTc) >/= 470 ms calculated from 3
electrocardiograms (ECGs) using Fredericia's Correction

7. Current or prior use of immunosuppressive medication within 28 days before the first
dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled
corticosteroids or systemic corticosteroids at physiological doses, which are not to
exceed 10 mg/day of prednisone, or an equivalent corticosteroid

8. Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects
with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within
the past 2 years) are not excluded.

9. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
ulcerative colitis)

10. History of primary immunodeficiency

11. History of allogeneic organ transplant

12. History of hypersensitivity to durvalumab or tremelimumab or any excipient

13. History of hypersensitivity to the combination or comparator agent (if applicable)

14. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
bleeding diatheses including any subject known to have evidence of acute or chronic
hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric
illness/social situations that would limit compliance with study requirements or
compromise the ability of the subject to give written informed consent

15. Known history of previous clinical diagnosis of tuberculosis

16. History of leptomeningeal carcinomatosis

17. Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving durvalumab or tremelimumab

18. Female subjects who are pregnant, breast-feeding or male or female patients of
reproductive potential who are not employing an effective method of birth control

19. Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results

20. Subjects with uncontrolled seizures