Atezolizumab + Pertuzumab + Trastuzumab In CNS Mets In BC

NCT03417544 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-546
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying a drug called atezolizumab as a possible treatment HER2-positive metastatic breast cancer (MBC) that has spread to the brain. The names of the study drugs involved in this study are:

• Atezolizumab
• Pertuzumab
• Trastuzumab

Conditions

HER2-positive Metastatic Breast Cancer; Central Nervous System Metastases

Keywords

HER2-positive metastatic Breast Cancer; Central Nervous System Metastases

Outcome Measures

Primary Outcomes (1)

• Confirmed Overall Response Rate in CNS

  The proportion of patients who had confirmed complete response or confirmed partial response, assessed using neuro-oncology-brain metastases (RANO-BM) criteria. RANO-BM assess the response of brain metastases to treatment, using MRI scan. There are four categories as results: Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD), which is separately defined as disappearance of all target lesions, at least a 30% decrease in the sum of the diameters of target lesions, neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as progressive disease (PD) and at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest) or the appearance of one or more new lesions.

  Participants were evaluated for response every 6 weeks for the first 24 weeks and then every 9 weeks thereafter, through study completion, an average of 24 weeks in the real study data

Secondary Outcomes (6)

• Objective Non-CNS Response Rates

  Participants were evaluated for response every 6 weeks for the first 24 weeks and then every 9 weeks thereafter, through study completion, an average of 24 weeks in the real study data

• Clinical Benefit Rate in CNS at 18 Weeks

  Participants were evaluated for response every 6 weeks for the first 24 weeks and then every 9 weeks thereafter, through study completion, an average of 24 weeks in the real study data

• Patient Reported Outcomes by MDASI-BT Stratified by CBR at 18 Weeks

  24 weeks

• Patient Reported Outcomes by EQ-5D Stratified by CBR at 18 Weeks

  24 weeks

• Investigator-Assessed Neurological Evaluation (NANO) Stratified by CBR at 18 Weeks

  24 weeks

Study Arms (1)

ATEZOLIZUMAB, PERTUZUMAB, TRASTUZUMAB

EXPERIMENTAL

Patients will receive the following treatment: * Atezolizumab (IV) every 3 weeks (q3w)\] * Pertuzumab (loading dose ), followed q3w thereafter by a predetermined dose in the protocol via IV) * High-dose Trastuzumab weekly for the first 24 weeks, and thereafter trastuzumab q3w).

Drug: ATEZOLIZUMAB; Drug: PERTUZUMAB; Drug: TRASTUZUMAB

Interventions

ATEZOLIZUMAB DRUG

(IV) every 3 weeks

Also known as: Tecentriq

ATEZOLIZUMAB, PERTUZUMAB, TRASTUZUMAB

PERTUZUMAB DRUG

Loading dose, followed every 3 weeks thereafter by a predetermined dose in the protocol via IV

Also known as: Perjeta

ATEZOLIZUMAB, PERTUZUMAB, TRASTUZUMAB

TRASTUZUMAB DRUG

Predetermined dose per protocol via IV, weekly for 24 weeks and after every 3 weeks

Also known as: Herceptin

ATEZOLIZUMAB, PERTUZUMAB, TRASTUZUMAB

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Eligibility will be assessed as part of the screening procedures for all patients.
• Pathologically confirmed HER2-positive MBC by local laboratory with the following requirements: HER2 overexpressed or amplified (immunohistochemistry of 3+ or HER2 gene amplification by in situ hybridization with a ratio of HER2-gene signals to centromere 17 signals ≥ 2.0 or average HER2 copy number ≥ 6.0 signals/cells).
• At least one measurable CNS metastasis, defined as ≥ 10 mm in at least one dimension
• Unequivocal evidence of new and/or progressive brain metastases, and at least one of the following scenarios:
• Treated with SRS or surgery with residual un-treated lesions remaining. Such participants are eligible for immediate enrollment on this study providing that at least one untreated lesion is measurable
• Participants who have had prior WBRT and/or SRS and then whose lesions have subsequently progressed are also eligible. In this case, lesions which have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression following SRS.
• Participants who have not previously been treated with cranial radiation (e.g., WBRT or SRS) are eligible to enter the study, but such participants must be asymptomatic from their CNS metastases and not requiring corticosteroids for symptom control.
• Both participants who present with systemic stable/absent or progressive disease are eligible to this trial, as long as they fulfill one of the above criteria.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (echo) or multigated acquisition (MUGA) scan within 28 days before day 1 of study.
• Stable dose of dexamethasone 2mg or less for at least 7 days prior to initiation of treatment
• Concurrent administration of other anti-cancer therapy during the course of this study is not allowed. Note that concurrent use of supportive care medications (e.g. anti-resorptive agents, pain medications) is allowed.
• The subject is 18 years old.
• Participants must have normal organ and marrow function as defined below:
• absolute neutrophil count ≥1,000/μl

You may not qualify if:

• Visceral crisis or impending visceral crisis at time of screening.
• CNS complications for whom urgent neurosurgical intervention is indicated (e.g., resection, shunt placement).
• Known leptomeningeal or brainstem metastases \[Defined as positive CSF cytology and/or unequivocal radiological evidence of clinically significant leptomeningeal involvement. CSF sampling is not required in the absence of suggestive symptoms to exclude leptomeningeal involvement\].
• Treatment with high dose systemic corticosteroids defined as dexamethasone \> 2mg/day or bioequivalent within 7 days of initiating therapy.
• Patients unable to undergo gadolinium contrast-enhanced MRI or receive IV contrast for any reason (e.g., due to pacemaker, ferromagnetic implants, claustrophobia, extreme obesity, hypersensitivity).
• Chemotherapy or targeted therapy within 14 days prior to cycle 1 day 1 of protocol therapy.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• No washout is required for endocrine therapy. If a patient has been on endocrine therapy within 28 days of study entry, that same endocrine therapy is permitted to be continued during protocol therapy, at the investigator's discretion, as is continuation of ovarian suppression in premenopausal women. Starting a new endocrine therapy during protocol therapy is not permitted
• Current use or history of receiving a non-approved, investigational treatment within 14 days prior to cycle 1 day 1 of protocol therapy
• Subjects with a history of hypersensitivity to compounds of similar biologic composition to atezolizumab or any constituent of the product
• The subject has an uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, congestive heart failure-New York Heart Association Class III or IV, active ischemic heart disease, myocardial infarction within the previous six months, uncontrolled diabetes mellitus, gastric or duodenal ulceration diagnosed within the previous 6 months, chronic liver or renal disease, or severe malnutrition.
• The subject is pregnant or breast-feeding
• No active, second potentially life-threatening cancer
• Has had major surgery within 21 days before cycle 1, day 1
• Active infection requiring iv antibiotics at day 1 of cycle 1

Sponsors & Collaborators

• Nancy Lin, MD: lead
• Genentech, Inc.: collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Interventions

atezolizumab; pertuzumab; Trastuzumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Nancy Lin, MD
• Organization: Dana-Farber Cancer Institute

Nancy_Lin@dfci.harvard.edu

617-632-3800

Study Officials

• Nancy Lin, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: January 16, 2018
• First Posted: January 31, 2018
• Study Start: May 21, 2018
• Primary Completion: May 20, 2020
• Study Completion: May 1, 2026
• Last Updated: April 27, 2026
• Results First Posted: May 7, 2024

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)