Single Arm Neoadjuvant Phase I/II Study of MEDI4736 (Anti-PD-L1 Antibody) Concomitant With Weekly Nab-paclitaxel and Dose-dense Doxorubicin/Cyclophosphamide (ddAC) Chemotherapy for Clinical Stage I-III Triple Negative Breast Cancer
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 respectively).
• 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 practice guidelines.
• Willing and able to provide written informed consent for voluntary participation in the trial.
• Willing to undergo a baseline tumor core needle biopsy and blood draws for correlative science studies.
• Eighteen years of age or older on the day of signing informed consent.
• Female subjects must either be of non-reproductive potential or must have a negative urine or serum pregnancy test upon study entry.
• 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 ULN
⁃ serum creatinine \< 1.5 x ULN or serum creatinine clearance \< 50mL/min
⁃ INR/PT/PTT each \< 1.5 x ULN
⁃ TSH within normal limits