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
  • For patients enrolled in the extended China enrollment phase: current resident of mainland China and of Chinese ancestry (the China subpopulation will consist of patients enrolled at sites in mainland China and Taiwan who are of Chinese ancestry)

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

Connecticut

New Haven
Yale University
Status: Active
Name Not Available

New York

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

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