Testing the Drug Atezolizumab or Placebo With Usual Therapy in First-Line HER2-Positive Metastatic Breast Cancer

Stopped early · Phase 3 · Has a placebo group

Conditions studied: Metastatic Breast Adenocarcinoma, Metastatic HER2-Positive Breast Carcinoma, Recurrent Breast Adenocarcinoma, Recurrent HER2-Positive Breast Carcinoma, Stage III Breast Cancer AJCC v7, Stage IV Breast Cancer AJCC v6 and v7, Unresectable Breast Carcinoma, Unresectable HER2-Positive Breast Carcinoma

In brief

This randomized phase III trial studies how well paclitaxel, trastuzumab, and pertuzumab with or without atezolizumab works in treating patients with breast cancer that has spread to other parts of the body (metastatic). Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Trastuzumab is a form of "targeted therapy" because it works by attaching itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Monoclonal antibodies, such as pertuzumab, may interfere with the ability of cancer cells to grow and spread. Immunotherapy with monoclonal antibodies, such as atezolizumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving paclitaxel, trastuzumab, and pertuzumab with or without atezolizumab may kill more tumor cells. \*NOTE: This study has a central confirmation step. The purpose of this step is to confirm by central testing that the patient's tumor has specific receptors. If the patient meets all the study requirements, the patient will join the study and begin therapy for breast cancer while the tumor is being tested.

Key facts

Study ID

NCT03199885

Run by

National Cancer Institute (NCI)

People needed

190

Starts

2019-04-05

Expected to finish

2025-04-04

Last updated by the study team

2026-05-29

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
• The trial is open to female and male patients
• Patients must be >= 18 years old
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Histologically confirmed adenocarcinoma of the breast with locally recurrent, unresectable disease or metastatic disease outside the central nervous system (CNS) confirmed as described below; eligible patients include those with either:
• De novo metastatic disease presenting without prior history of HER2-positive breast cancer:
• Diagnosis should have been made from a biopsy of a metastatic disease site, but biopsy from the breast primary or involved regional lymph nodes is acceptable if biopsy of the metastatic sites was thought to carry excessive risk for the patient
• Locally recurrent or metastatic disease following prior therapy for early breast cancer:
• Diagnosis must have been made from the biopsy of the locally recurrent or metastatic disease
• There must be an interval of >= 6 months between completion of neoadjuvant/adjuvant HER2-targeted therapy and documentation of locally recurrent or metastatic HER2-positive disease by biopsy
• Patients must have measurable disease based on RECIST 1.1, as determined by the site, which has not been irradiated to be eligible
• Patients with brain metastases are eligible if they meet ALL the following criteria:
• Four or fewer metastatic sites to CNS
• Largest unexcised tumor does not exceed 3 cm
• No metastases to brain stem, midbrain, pons, medulla or the optic nerves and chiasm
• Must have measurable disease outside the CNS, based on RECIST 1.1, as determined by the site, which has not been irradiated
• If patient presented with symptoms from CNS metastases, the symptoms must have resolved with initiation of steroids and initial local therapy (surgery, radiation therapy, or both)
• Must have been evaluated by Medical Oncologist and plan is to administer trastuzumab, pertuzumab, and a taxane as first-line systemic therapy
• May have received administration of trastuzumab OR lapatinib concurrently with radiation therapy for brain metastases. Toxicities related to lapatinib if administered, should be =< grade 1 per the CTCAE v5.0, and the lapatinib must have been completed at least 2 weeks prior to study entry
• No history of intracranial hemorrhage or spinal cord hemorrhage
• No neurosurgical resection or brain biopsy within 10 days prior to study entry
• After study entry and before randomization, send tissue for central HER2 confirmation; a tumor specimen obtained at the time of diagnosis of locally recurrent or metastatic disease must have been determined to be HER2-positive based on local testing according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines (Wolff 2018); HER2 status should initially be assessed using an Food and Drug Administration (FDA)-cleared IHC assay; positive is defined as IHC 3+ staining intensity; if HER2 IHC results are equivocal (2+), then HER2 status will be determined using a FDA-cleared HER2 in situ hybridization (ISH) test according to ASCO/CAP guidelines; Note: Once HER2-positive is confirmed on central testing, patients will be randomized to atezolizumab/placebo; randomization within 14 days from study entry will ensure that the Pharmaceutical Management Branch (PMB)-supplied agents will be received at the site for treatment on day 22 of cycle 1
• The tumor specimen obtained at the time of diagnosis used for HER2 testing must also have central testing for PD-L1 status; patients will be eligible irrespective of PD-L1 testing result including PD-L1 indeterminant
• The tumor specimen obtained at the time of diagnosis used for HER2 and PD-L1 testing should also have central testing for estrogen receptor (ER) and progesterone receptor (PgR) according to current ASCO/CAP guideline recommendations for hormone receptor testing; patients with < 1% ER and PgR staining by IHC will be classified as negative; if enough material for central confirmation of ER and PgR is unavailable, local testing results for ER and PgR may be used for eligibility
• Localized palliative radiation therapy to sites of non-measurable disease is allowed for symptom management and may begin prior to study entry and continue following study entry while receiving study therapy

You may not qualify if…

• Patients with brain metastases are excluded if they meet ANY of the following criteria:
• Symptoms from brain metastases have not resolved prior to study entry
• Five or more clearly identified foci of metastases to the brain
• Largest unexcised tumor exceeds 3 cm
• Spinal cord metastases
• Medical Oncologist plans to employ HER2-directed tyrosine kinase inhibitor as component of systemic therapy
• Metastatic disease limited to CNS
• Leptomeningeal carcinomatosis
• History of systemic anti-cancer therapy (e.g., chemotherapy, targeted therapy) for metastatic breast cancer (MBC) except as described in inclusion criteria
• History of exposure to cumulative doses of doxorubicin greater than 360 mg per square meter of body-surface area or its equivalent
• Prior treatment with mTOR inhibitors or CDK 4/6 inhibitors in combination with endocrine therapy for treatment of metastatic disease
• Prior treatment with CD137 agonists or immune checkpoint-blockade therapies, including anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to study entry
• Uncontrolled hypertension defined as sustained systolic blood pressure (BP) > 150 mmHg or diastolic BP > 90 mmHg; (patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria)
• History of asymptomatic LVEF decline to < 40% during or after prior HER2-targeted therapy even if the current LVEF is >= 50%
• Cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens; this includes but is not confined to:
• Active cardiac disease
• Angina pectoris that requires the current use of anti-anginal medication;
• Ventricular arrhythmias except for benign premature ventricular contractions;
• Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication;
• Conduction abnormality requiring a pacemaker;
• Valvular disease with documented compromise in cardiac function; or
• Symptomatic pericarditis
• History of cardiac disease
• Prior myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular (LV) function;

Where it is running

• Katmai Oncology Group — Anchorage, Alaska, United States
• Banner MD Anderson Cancer Center — Gilbert, Arizona, United States
• CTCA at Western Regional Medical Center — Goodyear, Arizona, United States
• Banner-University Medical Center Phoenix — Phoenix, Arizona, United States
• Banner Boswell Medical Center — Sun City, Arizona, United States
• NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro — Jonesboro, Arkansas, United States
• Kaiser Permanente-Anaheim — Anaheim, California, United States
• Kaiser Permanente-Deer Valley Medical Center — Antioch, California, United States
• Kaiser Permanente-Baldwin Park — Baldwin Park, California, United States
• Kaiser Permanente-Bellflower — Bellflower, California, United States
• Alta Bates Summit Medical Center-Herrick Campus — Berkeley, California, United States
• UC Irvine Health Cancer Center-Newport — Costa Mesa, California, United States
• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• Kaiser Permanente Dublin — Dublin, California, United States
• Kaiser Permanente-Fontana — Fontana, California, United States
• Kaiser Permanente-Fremont — Fremont, California, United States
• Palo Alto Medical Foundation-Fremont — Fremont, California, United States
• Washington Hospital — Fremont, California, United States
• Kaiser Permanente-Fresno — Fresno, California, United States
• Kaiser Permanente - Harbor City — Harbor City, California, United States
• Kaiser Permanente-Irvine — Irvine, California, United States
• Loma Linda University Medical Center — Loma Linda, California, United States
• Kaiser Permanente Los Angeles Medical Center — Los Angeles, California, United States
• Kaiser Permanente West Los Angeles — Los Angeles, California, United States
• University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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