Purpose

This is a Phase III, two-arm, randomized, double-blind placebo-controlled study in participants with HER2-positive primary breast cancer who have received preoperative chemotherapy and HER2-directed therapy, including trastuzumab followed by surgery, with a finding of residual invasive disease in the breast and/or axillary lymph nodes.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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: 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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Arm A: Placebo + Trastuzumab Emtansine
Participants will receive an intravenous (IV) infusion of placebo prior to the IV infusion of trastuzumab emtansine on Day 1 of each 21-day cycle for a total of 14 cycles.
  • Drug: Trastuzumab Emtansine
    Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg Q3W for 14 weeks.
    Other names:
    • Kadcyla, T-DM1, RO5304020
  • Drug: Placebo
    Placebo matched to atezolizumab will be administered at a dose of 1200 mg Q3W for 14 cycles.
  • Drug: Trastuzumab
    Trastuzumab will be used to complete 14 cycles of study treatment if trastuzumab emtansine is discontinued for toxicity not considered to be related to the trastuzumab component of the drug.
    Other names:
    • Herceptin
Experimental
Arm B: Atezolizumab + Trastuzumab Emtansine
Participants will receive an IV infusion of atezolizumab prior to the IV infusion of trastuzumab emtansine on Day 1 of each 21-day cycle for a total of 14 cycles.
  • Drug: Atezolizumab
    Atezolizumab will be administered at a dose of 1200 mg every three weeks (Q3W) for 14 cycles.
    Other names:
    • Tecentriq, RO5541267, MPDL3280A
  • Drug: Trastuzumab Emtansine
    Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg Q3W for 14 weeks.
    Other names:
    • Kadcyla, T-DM1, RO5304020
  • Drug: Trastuzumab
    Trastuzumab will be used to complete 14 cycles of study treatment if trastuzumab emtansine is discontinued for toxicity not considered to be related to the trastuzumab component of the drug.
    Other names:
    • Herceptin

Recruiting Locations

Mays Cancer Center at UT Health San Antonio MD Anderson Cancer
San Antonio, Texas 78229

More Details

Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: WO42633 https://forpatients.roche.com/
888-662-6728 (U.S. and Canada)
global-roche-genentech-trials@gene.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.