Description:
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.
Title
- Brief Title: 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
- Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Adjuvant Atezolizumab or Placebo and Trastuzumab Emtansine for HER2-Positive Breast Cancer at High Risk of Recurrence Following Preoperative Therapy
Clinical Trial IDs
- ORG STUDY ID:
WO42633
- SECONDARY ID:
2020-003681-40
- NCT ID:
NCT04873362
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Atezolizumab | Tecentriq, RO5541267, MPDL3280A | Arm B: Atezolizumab + Trastuzumab Emtansine |
Trastuzumab Emtansine | Kadcyla, T-DM1, RO5304020 | Arm A: Placebo + Trastuzumab Emtansine |
Placebo | | Arm A: Placebo + Trastuzumab Emtansine |
Trastuzumab | Herceptin | Arm A: Placebo + Trastuzumab Emtansine |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm A: Placebo + Trastuzumab Emtansine | Active Comparator | 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. | - Trastuzumab Emtansine
- Placebo
- Trastuzumab
|
Arm B: Atezolizumab + Trastuzumab Emtansine | Experimental | 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. | - Atezolizumab
- Trastuzumab Emtansine
- Trastuzumab
|
Eligibility Criteria
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: 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Invasive Disease-free Survival (IDFS) |
Time Frame: | From randomization up to approximately 6 years |
Safety Issue: | |
Description: | 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
Measure: | IDFS Including Second Primary Non-breast Invasive Cancer |
Time Frame: | From baseline up to 10 years |
Safety Issue: | |
Description: | |
Measure: | Disease-free Survival (DFS) |
Time Frame: | From baseline up to 10 years |
Safety Issue: | |
Description: | |
Measure: | Overall Survival (OS) |
Time Frame: | From baseline up to 10 years |
Safety Issue: | |
Description: | |
Measure: | Distant Recurrence-free Interval (DRFI) |
Time Frame: | From baseline up to 10 years |
Safety Issue: | |
Description: | |
Measure: | Number of Participants with Clinically Meaningful Deterioration in Global Health Status/Quality of Life (GHS/QoL) Physical, Role, and Cognitive Function |
Time Frame: | From baseline until 2 years after study treatment completion/discontinuation visit (approximately 3 years) |
Safety Issue: | |
Description: | 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) |
Measure: | Mean Absolute Scores in GHS/QoL, Physical, Role, and Cognitive Function, as Assessed Using the EORTC QLQ-C30 |
Time Frame: | From baseline until 2 years after study treatment completion/discontinuation visit (approximately 3 years) |
Safety Issue: | |
Description: | 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. |
Measure: | Mean Change From Baseline Scores in GHS/QoL, Physical, Role, and Cognitive Function, as Assessed Using the EORTC QLQ-C30 |
Time Frame: | From baseline until 2 years after study treatment completion/discontinuation visit (approximately 3 years) |
Safety Issue: | |
Description: | 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. |
Measure: | 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) |
Time Frame: | From baseline up to 10 years |
Safety Issue: | |
Description: | |
Measure: | Maximum Serum Concentrations (Cmax) for Atezolizumab |
Time Frame: | Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, Day 1 of Cycles 2, 3 and 8 pre-infusion (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) |
Safety Issue: | |
Description: | |
Measure: | Cmax for Trastuzumab Emtansine |
Time Frame: | Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) |
Safety Issue: | |
Description: | |
Measure: | Cmax for Total Trastuzumab |
Time Frame: | Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) |
Safety Issue: | |
Description: | |
Measure: | Cmax for DM1 |
Time Frame: | Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) |
Safety Issue: | |
Description: | DM1 = a thiol-containing maytansinoid anti-microtubule agent; N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine |
Measure: | Minimum Serum Concentrations (Cmin) for Atezolizumab |
Time Frame: | Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, Day 1 of Cycles 2, 3 and 8 (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) |
Safety Issue: | |
Description: | |
Measure: | Percentage of Participants with Anti-drug Antibodies (ADAs) to Atezolizumab |
Time Frame: | Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, Day 1 of Cycles 2, 3 and 8 (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) |
Safety Issue: | |
Description: | |
Measure: | Percentage of Participants with ADAs to Trastuzumab Emtansine |
Time Frame: | Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1) |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Hoffmann-La Roche |
Last Updated
August 6, 2021