A Study Evaluating the Efficacy and Safety of Adjuvant Atezolizumab or Placebo and Trastuzumab Emtansine for Participants With HER2-Positive Breast Cancer at High Risk of Recurrence Following Preoperative Therapy
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT04873362
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1188
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Placebo + Trastuzumab Emtansine Placebo Participants will receive an intravenous (IV) infusion of placebo prior to the IV infusion of trastuzumab emtansine on Day 1 of each 21-day cycle for a total of 14 cycles. Arm A: Placebo + Trastuzumab Emtansine Trastuzumab Emtansine Participants will receive an intravenous (IV) infusion of placebo prior to the IV infusion of trastuzumab emtansine on Day 1 of each 21-day cycle for a total of 14 cycles. Arm A: Placebo + Trastuzumab Emtansine Trastuzumab Participants will receive an intravenous (IV) infusion of placebo prior to the IV infusion of trastuzumab emtansine on Day 1 of each 21-day cycle for a total of 14 cycles. Arm B: Atezolizumab + Trastuzumab Emtansine Atezolizumab Participants will receive an IV infusion of atezolizumab prior to the IV infusion of trastuzumab emtansine on Day 1 of each 21-day cycle for a total of 14 cycles. Arm B: Atezolizumab + Trastuzumab Emtansine Trastuzumab Emtansine Participants will receive an IV infusion of atezolizumab prior to the IV infusion of trastuzumab emtansine on Day 1 of each 21-day cycle for a total of 14 cycles. Arm B: Atezolizumab + Trastuzumab Emtansine Trastuzumab Participants will receive an IV infusion of atezolizumab prior to the IV infusion of trastuzumab emtansine on Day 1 of each 21-day cycle for a total of 14 cycles.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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)
Trial Locations
- Locations (240)
Alabama Oncology
🇺🇸Birmingham, Alabama, United States
Roy and Patricia Disney Family Cancer Center- Providence Saint Joseph Medical Center
🇺🇸Buena, California, United States
UCLA Medical Center
🇺🇸Santa Monica, California, United States
Innovation Clinical Research Institute
🇺🇸Whittier, California, United States
Florida Cancer Specialists
🇺🇸West Palm Beach, Florida, United States
Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital
🇺🇸Carrollton, Georgia, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
New England Cancer Specialists
🇺🇸Westbrook, Maine, United States
The Valley Hospital
🇺🇸Paramus, New Jersey, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Scroll for more (230 remaining)Alabama Oncology🇺🇸Birmingham, Alabama, United States