Purpose

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).

Condition

Eligibility

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

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

Study Design

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

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Atezolizumab +ddAC-PacHP
Participants will receive atezolizumab 840 mg IV Q2W for 4 cycles during neoadjuvant phase with ddAC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 IV), followed by atezolizumab 1200 mg IV Q3W for 4 cycles with paclitaxel 80 mg/m2 IV weekly for 12 continuous weeks, trastuzumab 6 mg/kg IV (with an initial 8-mg/kg IV loading dose) Q3W for 4 cycles, and pertuzumab 420 mg IV (with an initial 840-mg IV loading dose) Q3W for 4 cycles. During the adjuvant phase, participants will continue to receive the following study treatments Q3W to complete up to 1 year of HER2-target therapy inclusive of therapy given both in the neoadjuvant and adjuvant setting: atezolizumab 1200 mg IV Q3W, trastuzumab 6 mg/kg IV (with an initial 8-mg/kg IV loading dose) Q3W, and pertuzumab 420 mg IV (with an initial 840-mg IV loading dose) Q3W. Participants who do not achieve pCR have the option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles.
  • Drug: Atezolizumab
    Atezolizumab will be administered as per the schedule specified in the respective arm.
    Other names:
    • Tecentriq
  • Drug: Doxorubicin
    Doxorubicin will be administered as per the schedule specified in the respective arm.
    Other names:
    • Adriamycin
  • Drug: Cyclophosphamide
    Cyclophosphamide will be administered as per the schedule specified in the respective arm.
    Other names:
    • Cytoxan
    • Neosar
  • Drug: Paclitaxel
    Paclitaxel will be administered as per the schedule specified in the respective arm.
    Other names:
    • Taxol
  • Drug: Trastuzumab
    Trastuzumab will be administered as per the schedule specified in the respective arm.
    Other names:
    • Herceptin
  • Drug: Pertuzumab
    Pertuzumab will be administered as per the schedule specified in the respective arm.
    Other names:
    • Perjeta
  • Drug: Trastuzumab Emtansine
    Participants without pCR have the option of receiving adjuvant atezolizumab/placebo combined with Trastuzumab Emtansine 3.6 mg/kg IV Q3W.
    Other names:
    • Kadcyla
Placebo Comparator
Placebo + ddAC-PacHP
Participants will receive placebo 840 mg IV Q2W for 4 cycles during neoadjuvant phase with ddAC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 IV), followed by placebo 1200 mg IV Q3W for 4 cycles with paclitaxel 80 mg/m2 IV weekly for 12 continuous weeks, trastuzumab 6 mg/kg IV (with an initial 8-mg/kg IV loading dose) Q3W for 4 cycles, and pertuzumab 420 mg IV (with an initial 840-mg IV loading dose) Q3W for 4 cycles. During the adjuvant phase, participants will continue to receive the following study treatments Q3W to complete up to 1 year of HER2-target therapy inclusive of therapy given both in the neoadjuvant and adjuvant setting: placebo 1200 mg IV Q3W, trastuzumab 6 mg/kg IV (with an initial 8-mg/kg IV loading dose) Q3W, and pertuzumab 420 mg IV (with an initial 840-mg IV loading dose) Q3W. Participants who do not achieve pCR have the option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles.
  • Drug: Placebo
    Placebo matched to atezolizumab will be administered as per the schedule specified in the respective arm.
  • Drug: Doxorubicin
    Doxorubicin will be administered as per the schedule specified in the respective arm.
    Other names:
    • Adriamycin
  • Drug: Cyclophosphamide
    Cyclophosphamide will be administered as per the schedule specified in the respective arm.
    Other names:
    • Cytoxan
    • Neosar
  • Drug: Paclitaxel
    Paclitaxel will be administered as per the schedule specified in the respective arm.
    Other names:
    • Taxol
  • Drug: Trastuzumab
    Trastuzumab will be administered as per the schedule specified in the respective arm.
    Other names:
    • Herceptin
  • Drug: Pertuzumab
    Pertuzumab will be administered as per the schedule specified in the respective arm.
    Other names:
    • Perjeta
  • Drug: Trastuzumab Emtansine
    Participants without pCR have the option of receiving adjuvant atezolizumab/placebo combined with Trastuzumab Emtansine 3.6 mg/kg IV Q3W.
    Other names:
    • Kadcyla

Recruiting Locations

Cancer Therapy and Research Center CTRC at UTHSCSA
San Antonio, Texas 78229

More Details

NCT ID
NCT03726879
Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: BO40747 www.roche.com/about_roche/roche_worldwide.htm
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.