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NCT Number: NCT04873362

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Macarthur Cancer Therapy Centre, Campbelltown, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Atezolizumab

Drug

Atezolizumab will be administered at a dose of 1200 mg every three weeks (Q3W) for 14 cycles.

Other names: Tecentriq, RO5541267, MPDL3280A

Trastuzumab Emtansine

Drug

Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg Q3W for 14 weeks.

Other names: Kadcyla, T-DM1, RO5304020

Placebo

Drug

Placebo matched to atezolizumab will be administered at a dose of 1200 mg Q3W for 14 cycles.

Trastuzumab

Drug

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.

Other names: Herceptin

Primary outcomes

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

    Time frame: 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 outcomes

  1. 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])

  2. IDFS in the PD-L1-positive and the PD-L1-negative Population

    Time frame: 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).

  3. 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)

  4. Overall Survival (OS)

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

  5. Distant Recurrence-free Interval (DRFI)

    Time frame: From baseline until distant disease recurrence, through the end of study (approximately 10 years from LPI)

  6. 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)

    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)

  7. 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)

    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.

  8. 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)

    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.

  9. 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

  10. Maximum Serum Concentrations (Cmax) for Atezolizumab

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

  11. 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)

  12. Cmax for Trastuzumab Emtansine

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

  13. 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)

  14. Cmax for Total Trastuzumab

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

  15. 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)

  16. Cmax for DM1

    Time frame: 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

  17. 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)

  18. 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)

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Acronym: Astefania

Important dates

Study start
2021
Primary completion
2028
Study completion
2034
First posted
May 5, 2021
Registry last updated
Mar 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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