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

Phase 3Active Not RecruitingNCT04873362

Hoffmann-La Roche1,188 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

1,188

Conditions

Breast Cancer

Interventions

AtezolizumabDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (239)

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

Outcomes

Primary Outcomes

Invasive Disease-free Survival (IDFS) in the Full Analysis Set (FAS)

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.

Time frame: From baseline until the first occurrence of iDFS event or death, through primary analysis data cut off (approximately 7 years)

Secondary Outcomes

IDFS Including Second Primary Non-breast Invasive Cancer

Time frame: 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

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).

Time frame: From baseline until the first occurrence of iDFS event or death, through the end of study (approximately 10 years from LPI)

Disease-free Survival (DFS)

Time frame: From baseline until the first occurrence of DFS event or death, through the end of study (approximately 10 years from LPI)

Overall Survival (OS)

Time frame: From baseline to death from any cause through the end of study (approximately 10 years from LPI)

Distant Recurrence-free Interval (DRFI)

Time frame: 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

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)

Time frame: From baseline until 2 years after study treatment completion/discontinuation visit (approximately 3 years)

Mean Absolute Scores in GHS/QoL, Physical, Role, and Cognitive Function, as Assessed Using the EORTC QLQ-C30

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.

Time frame: From baseline until 2 years after study treatment completion/discontinuation visit (approximately 3 years)

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)

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

Maximum Serum Concentrations (Cmax) for Atezolizumab

Time frame: Day 1 of Cycles 1 and 4 after 30 minutes post-infusion (a cycle=21 days)

Minimum Serum Concentrations (Cmin) for Atezolizumab

Time frame: 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

Time frame: Day 1 of Cycles 1 and 4 after 30 minutes post-infusion (a cycle=21 days)

Cmin for Trastuzumab Emtansine

Time frame: 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

Time frame: Day 1 of Cycles 1 and 4 after 30 minutes post-infusion (a cycle=21 days)

Cmin for Total Trastuzumab

Time frame: 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

DM1 = a thiol-containing maytansinoid anti-microtubule agent; N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine

Time frame: Day 1 of Cycles 1 and 4 after 30 minutes post-infusion (a cycle=21 days)

Percentage of Participants with Anti-drug Antibodies (ADAs) to Atezolizumab

Time frame: 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

Time frame: 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)