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

Status: Active

Description

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

Locations & Contacts

New York

New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: Active
Name Not Available

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: Active
Name Not Available

Texas

San Antonio
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
Status: Active
Contact: Sonia Lisa Creighton
Phone: 210-450-1366
Email: creighton@uthscsa.edu

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
Hoffmann-La Roche

Trial IDs

Primary ID BO40747
Secondary IDs NCI-2019-00318
Clinicaltrials.gov ID NCT03726879