Overview

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, not recruiting
Trial end date:
2023-08-24
Target enrollment:
0
Participant gender:
All
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).
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Hoffmann-La Roche
Collaborator:
Chugai Pharmaceutical
Treatments:
Ado-Trastuzumab Emtansine
Albumin-Bound Paclitaxel
Antibodies, Monoclonal
Atezolizumab
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Maytansine
Paclitaxel
Pertuzumab
Trastuzumab
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