Breast Cancer
Conditions
Brief summary
This is a Phase III, two-arm, randomized, double-blind placebo-controlled study in participants with HER2-positive primary breast cancer who have received preoperative chemotherapy and HER2-directed therapy, including trastuzumab followed by surgery, with a finding of residual invasive disease in the breast and/or axillary lymph nodes. As of June 4, 2024, this study is no longer accepting any newly screened participants.
Interventions
DRUGAtezolizumab
Atezolizumab will be administered at a dose of 1200 mg every three weeks (Q3W) for 14 cycles.
DRUGTrastuzumab Emtansine
Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg Q3W for 14 weeks.
DRUGPlacebo
Placebo matched to atezolizumab will be administered at a dose of 1200 mg Q3W for 14 cycles.
DRUGTrastuzumab
Trastuzumab will be used to complete 14 cycles of study treatment if trastuzumab emtansine is discontinued for toxicity not considered to be related to the trastuzumab component of the drug.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed invasive breast carcinoma * Centrally-confirmed human epidermal growth factor receptor 2 (HER2)-positive invasive breast cancer * Centrally confirmed PD-L1 and hormone receptor status * Clinical stage at disease presentation (prior to neoadjuvant therapy): cT4/anyN/M0, any cT/N2-3/M0, or cT1-3/N0-1/M0 (participants with cT1mi/T1a/T1b/N0 are not eligible) * Completion of pre-operative systemic chemotherapy including at least 9 weeks of taxane and 9 weeks of trastuzumab (anthracycline and/or additional HER2-targeted agents are permitted) * \<=12 weeks between primary surgery and randomization * Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 * Screening left ventricular ejection fraction (LVEF) \>= 50% and no decrease in LVEF by \>15% from the pre-chemotherapy LVEF. If no pre-chemotherapy LVEF, screening LVEF \>= 55% * Life expectancy \>= 6 months * Adequate hematologic and end organ function
Exclusion criteria
* Stage IV breast cancer * An overall response of disease progression according to the investigator at the conclusion of preoperative systemic therapy * Prior treatment with T-DM1, or atezolizumab, or other immune checkpoint inhibitors * History of exposure to various cumulative doses of anthracyclines * History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or ductal carcinoma in situ (DCIS) * Current grade \>=2 peripheral neuropathy * History of idiopathic pulmonary fibrosis, organizing pneumonia, or pneumonitis * History of or active autoimmune disease or immune deficiency * Treatment with immunostimulatory or immunosuppressive agents * Cardiopulmonary dysfunction * Any known active liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Invasive Disease-free Survival (IDFS) in the Full Analysis Set (FAS) | From baseline until the first occurrence of iDFS event or death, through primary analysis data cut off (approximately 7 years) | IDFS event is defined as the time from randomization to the first occurrence of the following events: ipsilateral invasive breast tumor recurrence, ipsilateral local-regional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| IDFS Including Second Primary Non-breast Invasive Cancer | From baseline until the first occurrence of iDFS event or death, through the end of study (approximately 10 years from last participant in [LPI]) | — |
| IDFS in the PD-L1-positive and the PD-L1-negative Population | From baseline until the first occurrence of iDFS event or death, through the end of study (approximately 10 years from LPI) | Defined as all randomized participants from the ITT population with a centrally assessed PD-L1-positive \[i.e., PD-L1 status of IC1/2/3\] or PD-L1-negative status \[i.e.,PD-L1 status of IC0\] at randomization as per corresponding stratification factors recorded in the interactive web-based response system (IWRS). |
| Disease-free Survival (DFS) | From baseline until the first occurrence of DFS event or death, through the end of study (approximately 10 years from LPI) | — |
| Overall Survival (OS) | From baseline to death from any cause through the end of study (approximately 10 years from LPI) | — |
| Distant Recurrence-free Interval (DRFI) | From baseline until distant disease recurrence, through the end of study (approximately 10 years from LPI) | — |
| Number of Participants with Clinically Meaningful Deterioration in Global Health Status/Quality of Life (GHS/QoL) Physical, Role, and Cognitive Function | From baseline until 2 years after study treatment completion/discontinuation visit (approximately 3 years) | Clinically Meaningful Deterioration will be Measured by Scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer (EORTC QLQ C30) |
| Mean Absolute Scores in GHS/QoL, Physical, Role, and Cognitive Function, as Assessed Using the EORTC QLQ-C30 | From baseline until 2 years after study treatment completion/discontinuation visit (approximately 3 years) | The European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) is a self-reported measure. Functioning and symptoms items are scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. GHS and QoL items are scored on a 7-point scale: 1=Very poor, 2, 3, 4, 5, 6, 7=Excellent. Scores will be transformed to a range of 0 to 100, with higher scores (i.e. closer to 100) reflecting better functioning, better GHS/QoL, and worse symptoms. |
| Mean Change From Baseline Scores in GHS/QoL, Physical, Role, and Cognitive Function, as Assessed Using the EORTC QLQ-C30 | From baseline until 2 years after study treatment completion/discontinuation visit (approximately 3 years) | The European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) is a self-reported measure. Functioning and symptoms items are scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. GHS and QoL items are scored on a 7-point scale: 1=Very poor, 2, 3, 4, 5, 6, 7=Excellent. Scores will be transformed to a range of 0 to 100, with higher scores (i.e. closer to 100) reflecting better functioning, better GHS/QoL, and worse symptoms. |
| Percentage of Participants with Adverse Events (AEs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | From baseline up to 10 years | — |
| Maximum Serum Concentrations (Cmax) for Atezolizumab | Day 1 of Cycles 1 and 4 after 30 minutes post-infusion (a cycle=21 days) | — |
| Minimum Serum Concentrations (Cmin) for Atezolizumab | Pre-infusion on Day 1 of Cycles 1, 2, 3, 4 and 8 (a cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) | — |
| Cmax for Trastuzumab Emtansine | Day 1 of Cycles 1 and 4 after 30 minutes post-infusion (a cycle=21 days) | — |
| Cmin for Trastuzumab Emtansine | Pre-infusion on Day 1 of Cycles 1 and 4 (a cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) | — |
| Cmax for Total Trastuzumab | Day 1 of Cycles 1 and 4 after 30 minutes post-infusion (a cycle=21 days) | — |
| Cmin for Total Trastuzumab | Pre-infusion on Day 1 of Cycles 1 and 4 (a cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) | — |
| Cmax for DM1 | Day 1 of Cycles 1 and 4 after 30 minutes post-infusion (a cycle=21 days) | DM1 = a thiol-containing maytansinoid anti-microtubule agent; N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine |
| Percentage of Participants with Anti-drug Antibodies (ADAs) to Atezolizumab | Pre-infusion on Day 1 of Cycles 1, 2, 3, 4 and 8 (a cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) | — |
| Percentage of Participants with ADAs to Trastuzumab Emtansine | Pre-infusion on Day 1 of Cycles 1 and 4 (a cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) | — |
Countries
Australia, Austria, Belgium, Brazil, Bulgaria, China, Czechia, Denmark, France, Germany, Greece, Hong Kong, Hungary, India, Italy, Kenya, Mexico, New Zealand, Poland, Portugal, Romania, Russia, Singapore, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), Uganda, Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed