A Study To Evaluate the Efficacy and Safety Of Atezolizumab or Placebo in Combination With Neoadjuvant Doxorubicin + Cyclophosphamide Followed By Paclitaxel + Trastuzumab + Pertuzumab In Early Her2-Positive Breast Cancer
A Study To Evaluate the Efficacy and Safety Of Atezolizumab or Placebo in Combination With Neoadjuvant Doxorubicin + Cyclophosphamide Followed By Paclitaxel + Trastuzumab + Pertuzumab In Early Her2-Positive Breast Cancer
This study (also known as IMpassion050) will evaluate the efficacy and safety of atezolizumab
 compared with placebo when given in combination with neoadjuvant dose-dense anthracycline
 (doxorubicin) + cyclophosphamide followed by paclitaxel + trastuzumab + pertuzumab
 (ddAC-PacHP) in patients with early HER2-positive breast cancer (T2-4, N1-3, M0).
Inclusion Criteria:

 -  Confirmed diagnosis of HER2-positive breast cancer, and hormonal and PD-L1 status, as
 documented through central testing of a representative tumor tissue specimen

 -  Primary breast tumor size of > 2 cm by any radiographic measurement

 -  Stage at presentation: T2-T4, N1-N3, M0 as determined by AJCC staging system, 8th
 edition

 -  Pathologic confirmation of nodal involvement with malignancy must be determined by
 fine needle aspiration or core-needle biopsy. Surgical excision of lymph nodes is not
 permitted.

 -  Patients with multifocal tumors are eligible provided at least one focus is sampled
 and centrally confirmed as HER2-positive.

 -  Patients with multicentric tumors are eligible provided all discrete lesions are
 sampled and centrally confirmed as HER2-positive.

 -  Eastern Cooperative Oncology Group Performance Status of 0 or 1

 -  Baseline LVEF >= 55% measured by echocardiogram (ECHO) or multiple-gated acquisition
 (MUGA) scans

 -  Adequate hematologic and end-organ function obtained within 14 days prior to
 initiation of study treatment

 -  For women of childbearing potential: agreement to remain abstinent or use
 contraceptive methods, and agreement to refrain from donating eggs

 -  For men: agreement to remain abstinent or use contraceptive measures, and agreement to
 refrain from donating sperm

 Exclusion Criteria:

 -  Prior history of invasive breast cancer

 -  Stage IV (metastatic) breast cancer

 -  Patients with synchronous bilateral invasive breast cancer

 -  Prior systemic therapy for treatment of breast cancer

 -  Previous therapy with anthracyclines or taxanes for any malignancy

 -  Ulcerating or inflammatory breast cancer

 -  Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph
 nodes

 -  Sentinel lymph node procedure or axillary lymph node dissection prior to initiation of
 neoadjuvant therapy

 -  History of other malignancy within 5 years prior to screening, with the exception of
 those patients who have a negligible risk of metastasis or death

 -  Cardiopulmonary dysfunction

 -  Dyspnea at rest

 -  Active or history of autoimmune disease or immune deficiency

 -  Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment
 or within 5 months after the final dose of atezolizumab/placebo, 6 months after the
 final dose of doxorubicin, 12 months after the final dose of cyclophosphamide, 6
 months after the final dose of paclitaxel, or 7 months after the final dose of
 trastuzumab, pertuzumab, or trastuzumab emtansine whichever occurs last

 Exclusion Criteria Related to Trastuzumab Emtansine in the Adjuvant Setting:

 -  Patients who achieved pCR

 -  Evidence of clinically evident gross residual or recurrent disease following
 neoadjuvant therapy and surgery

 -  Unable to complete surgery with curative intent after conclusion of neoadjuvant
 systemic therapy

 -  Patient discontinued treatment with trastuzumab because of toxicity during the
 neoadjuvant phase of the study

 -  Clinically significant history of liver disease, including cirrhosis, current alcohol
 abuse, autoimmune hepatic disorders, or sclerosis cholangitis

 -  Patients with Grade >=2 peripheral neuropathy

 -  Prior treatment with trastuzumab emtansine