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 (IMpassion050)
Status and phase
Completed
Phase 3
Conditions
Breast Cancer
Treatments
Drug: Placebo
Drug: Cyclophosphamide
Drug: Atezolizumab
Drug: Paclitaxel
Drug: Doxorubicin
Drug: Trastuzumab
Drug: Trastuzumab Emtansine
Drug: Pertuzumab
Details and patient eligibility
About
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).
Enrollment
454 patients
Sex
All
Ages
18+ years old
Volunteers
No Healthy Volunteers
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
Trial design
Primary purpose
Treatment
Allocation
Randomized
Interventional model
Parallel Assignment
Masking
Double Blind
454 participants in 2 patient groups, including a placebo group
Atezolizumab +ddAC-PacHP
Experimental group
Description:
Participants will receive atezolizumab (atezo) 840 mg IV Q2W for 4 cycles during neoadjuvant phase with ddAC (doxorubicin 60 mg/m2 \& cyclophosphamide 600 mg/m2 IV), followed by atezo 1200 mg IV Q3W for 4 cycles with paclitaxel 80 mg/m2 IV weekly for 12 continuous weeks, trastuzumab 6 mg/kg IV (with initial 8mg/kg IV loading dose) Q3W for 4 cycles, \& pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W for 4 cycles. During adjuvant phase, participants will continue to receive following study treatments Q3W to complete up to 1 year HER2-target therapy inclusive of therapy given both in neoadjuvant and adjuvant setting: atezo 1200 mg IV Q3W, trastuzumab 6 mg/kg IV (with initial 8-mg/kg IV loading dose) Q3W, \& pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W. Participants who do not achieve pCR have option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo must be discontinued.
Treatment:
Drug: Pertuzumab
Drug: Trastuzumab Emtansine
Drug: Trastuzumab
Drug: Paclitaxel
Drug: Doxorubicin
Drug: Atezolizumab
Drug: Cyclophosphamide
Placebo + ddAC-PacHP
Placebo Comparator group
Description:
Participants will receive placebo 840 mg IV Q2W for 4 cycles during neoadjuvant phase with ddAC (doxorubicin 60 mg/m2 \& 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 initial 8-mg/kg IV loading dose) Q3W for 4 cycles \& pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W for 4 cycles. During adjuvant phase, participants will continue to receive following study treatments Q3W to complete up to 1 year HER2-target therapy inclusive of therapy given both in neoadjuvant \& adjuvant setting: placebo 1200 mg IV Q3W, trastuzumab 6 mg/kg IV (with initial 8-mg/kg IV loading dose) Q3W, \& pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W. Participants who do not achieve pCR have option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo must be discontinued.
Treatment:
Drug: Pertuzumab
Drug: Trastuzumab Emtansine
Drug: Trastuzumab
Drug: Paclitaxel
Drug: Doxorubicin
Drug: Cyclophosphamide
Drug: Placebo
Trial contacts and locations
76
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal
© Copyright 2025 Veeva Systems