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
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Atezolizumab; Placebo; Doxorubicin; Cyclophosphamide; Paclitaxel; Trastuzumab; Pertuzumab; Trastuzumab Emtansine
Intervention description: Atezolizumab will be administered as per the schedule specified in the respective arm.; Placebo matched to atezolizumab will be administered as per the schedule specified in the respective arm.; Doxorubicin will be administered as per the schedule specified in the respective arm.; Cyclophosphamide will be administered as per the schedule specified in the respective arm.; Paclitaxel will be administered as per the schedule specified in the respective arm.; Trastuzumab will be administered as per the schedule specified in the respective arm.; Pertuzumab will be administered as per the schedule specified in the respective arm.; Participants without pCR have the option of receiving adjuvant atezolizumab/placebo combined with Trastuzumab Emtansine 3.6 mg/kg IV Q3W.
Intervention MeSH terms: Paclitaxel; Maytansine; Ado-Trastuzumab Emtansine; Cyclophosphamide; Doxorubicin; Trastuzumab; Atezolizumab; Pertuzumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 454.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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).
    

Eligibility criteria:

        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