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
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
- Breast Cancer
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
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Atezolizumab +ddAC-PacHP |
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. |
|
|
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 & 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. |
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More Details
- Status
- Completed
- Sponsor
- Hoffmann-La Roche