A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Adjuvant Atezolizumab or Placebo and Trastuzumab Emtansine for HER2-Positive Breast Cancer at High Risk of Recurrence Following Preoperative Therapy

Inclusion Criteria:

• Histologically confirmed invasive breast carcinoma
• Centrally-confirmed human epidermal growth factor receptor 2 (HER2)-positive invasive breast cancer
• Centrally confirmed PD-L1 and hormone receptor status
• Clinical stage at disease presentation (prior to neoadjuvant therapy): cT4/anyN/M0, any cT/N2-3/M0, or cT1-3/N0-1/M0 (participants with cT1mi/T1a/T1b/N0 are not eligible)
• Completion of pre-operative systemic chemotherapy including at least 9 weeks of taxane and 9 weeks of trastuzumab (anthracycline and/or additional HER2-targeted agents are permitted)
• <=12 weeks between primary surgery and randomization
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
• Screening left ventricular ejection fraction (LVEF) >= 50% and no decrease in LVEF by >15% from the pre-chemotherapy LVEF. If no pre-chemotherapy LVEF, screening LVEF >= 55%
• Life expectancy >= 6 months
• Adequate hematologic and end organ function

Exclusion Criteria:

• Stage IV breast cancer
• An overall response of disease progression according to the investigator at the conclusion of preoperative systemic therapy
• Prior treatment with T-DM1, or atezolizumab, or other immune checkpoint inhibitors
• History of exposure to various cumulative doses of anthracyclines
• History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or ductal carcinoma in situ (DCIS)
• Current grade >=2 peripheral neuropathy
• History of idiopathic pulmonary fibrosis, organizing pneumonia, or pneumonitis
• History of or active autoimmune disease or immune deficiency
• Treatment with immunostimulatory or immunosuppressive agents
• Cardiopulmonary dysfunction
• Any known active liver disease

• Primary
  • IDFS
• Secondary
  • DFS
  • OS
  • QOL
  • Safety