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 (Astefania)

Roche

Status and phase: Enrolling; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Trastuzumab Emtansine; Drug: Placebo; Drug: Trastuzumab; Drug: Atezolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04873362

WO42633

2020-003681-40 (EudraCT Number)

2023-503568-18-00 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 1,150 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,150 participants in 2 patient groups

Arm A: Placebo + Trastuzumab Emtansine

Active Comparator group

Description:

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.

Treatment:

Drug: Trastuzumab

Drug: Placebo

Drug: Trastuzumab Emtansine

Arm B: Atezolizumab + Trastuzumab Emtansine

Experimental group

Description:

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.

Treatment:

Drug: Trastuzumab

Drug: Atezolizumab

Drug: Trastuzumab Emtansine