The purpose of the study is to address the following hypotheses: (i) Anti-PD-L1 therapy with
MEDI4736 administered concomitantly with weekly nab-paclitaxel followed by MEDI4736
concomitant with ddAC neoadjuvant chemotherapy will induce higher pathologic complete
response (pCR) rate (>55%) in triple negative breast cancer than historical pCR rates
(30-40%) observed with chemotherapy alone. (ii) MEDI4736 can be safely co-administered at
full dose with sequential with nab-paclitaxel (100mg/m2) and ddAC (60 mg/m2 and 600 mg/m2
The primary objective of the Phase I portion of the trial is to assess the safety of MEDI4736
combined with chemotherapy and determine if full dose of MEDI4736 can be administered
concomitantly with full dose weekly nab-paclitaxel followed by dose-dense AC chemotherapies,
The primary objective of the Phase II portion of the study is to estimate the pCR rate with
MEDI4736 in combination with weekly nab-paclitaxel x 12 treatments followed by MEDI4736 in
combination with ddAC x 4 treatments for estrogen receptor (ER), progesterone receptor (PR)
and HER2 negative (triple negative, TNBC), clinical stage I-III breast cancer. Pathologic
complete response is defined as the absence of residual invasive cancer on hematoxylin and
eosin evaluation of the resected breast specimen and all sampled regional lymph nodes
following completion of neoadjuvant systemic therapy (i.e. ypT0/Tis ypN0).
Secondary objectives include: to assess the safety and toxicity of adding anti-PD-L1
antibody, MEDI4736 to standard of care neoadjuvant chemotherapy in the Phase II portion of
the trial. The study will also monitor for events of special clinical interest with a
suspected auto-immunologic etiology including grade ≥3 colitis, hyperthyroidism,
hypophysitis, hypothyroidism, pneumonitis, rash and anti-drug-antibody (ADA) immune complex
disease (manifested by symptoms of arthralgias, abdominal pain, back pain, and vasculitis).
Exploratory objectives include: to assess correlation between response to therapy and immune
parameters of the tumor at baseline and post-treatment in patients who have residual cancer
1. Newly diagnosed histologically confirmed stage I-III, ER, PR and HER2 negative
invasive breast cancer as defined by the ASCO CAP guidelines for whom systemic
chemotherapy would be indicated based on physician judgment following standard NCCN
2. Willing and able to provide written informed consent for voluntary participation in
3. Willing to undergo a baseline tumor core needle biopsy and blood draws for correlative
4. Eighteen years of age or older on the day of signing informed consent.
5. Female subjects must either be of non-reproductive potential or must have a negative
urine or serum pregnancy test upon study entry.
6. Patients should have adequate organ function to tolerate chemotherapy, as defined by:
- peripheral granulocyte count of > 1,500/mm3
- platelet count > 100,000/mm3
- hemoglobin >9 g/dL
- total bilirubin < 1.5 x upper limit of normal (ULN)
- aspartate aminotransferase (AST) and alanine aminotransferase (ALT) each < 1.5 x
- serum creatinine < 1.5 x ULN or serum creatinine clearance < 50mL/min
- INR/PT/PTT each < 1.5 x ULN
- TSH within normal limits
1. Patients who underwent partial excisional biopsy or lumpectomy, segmental mastectomy
or modified radical mastectomy or sentinel node.
2. Patients for whom anthracycline, paclitaxel or antibody therapies are contraindicated.
3. Patients with active autoimmune disease or documented autoimmune disease within 2
years. Patients with hypothyroidism that is clinically stable and have normal TSH
levels with hormone replacement, or patients with vitiligo or psoriasis not requiring
treatment remain eligible for the study.
4. Active or prior documented inflammatory bowel disease (Crohn's disease, ulcerative
5. Patients with known active hepatitis B or C or HIV infection or with history of