A Study of Izalontamab Brengitecan Versus Chemotherapy in Participants With Previously Untreated, Locally Advanced, Recurrent Inoperable, or Metastatic Triple-negative Breast Cancer Ineligible for Anti-PD(L)1 Drugs (IZABRIGHT-Breast01)
The purpose of this study is to assess the efficacy and safety of iza-bren, a bi-specific antibody-drug conjugate against EGFR and HER3 with a topoisomerase inhibitor payload versus treatment of physician's choice (TPC) (paclitaxel, nab-paclitaxel, carboplatin plus gemcitabine, and capecitabine) for the treatment of first-line metastatic triple-negative breast cancer (TNBC) or estrogen receptor (ER)-low, human epidermal growth factor receptor 2 (HER2)-negative BC patients who are not candidates for anti-PD(L)1 therapy and endocrine therapies.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria
* Histologically or cytologically confirmed and documented locally-advanced, recurrent inoperable, or metastatic triple-negative breast cancer (TNBC) (ER \< 1%, PgR \< 1%, HER2 IHC 0, 1+, or 2+ with ISH negative for HER2 gene amplification) or ER-low, HER2-negative BC (ER and / or PgR 1% to 10%, HER2 IHC 0, 1+, or 2+ with ISH negative for HER2 gene amplification) per American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, based on the most recently analyzed biopsy or other pathology specimen.
* Patients with recurrent disease must have experienced disease relapse at least 6 months after finishing their last therapy with curative intent.
* Participants with TNBC must be considered ineligible for 1L chemotherapy combination treatment with an anti-PD-1 (eg, pembrolizumab) or an anti-PD-L1 (eg, atezolizumab) due to any one of the following criteria:
i) Investigator-determined ineligibility based on PD-L1 negative disease determined and documented prior to trial screening as part of standard of care (SoC); ii) Has experienced disease relapse between 6 to 12 months after the completion of (neo)adjuvant therapy with an anti-PD(L)1; iii) Has a severe auto-immune disease or other contraindication, in the opinion of the investigator, for the use of an anti-PD(L)1 drug: iv) Any auto-immune disease that requires current immunosuppression (eg, methotrexate, cyclophosphamide, prednisone \> 10 mg/day).
v) Prior auto-immune AE to peri-adjuvant ICI that required immunosuppression. vi) Current Graves' disease with ophthalmopathy or in need of radioiodine or in use of antithyroid medication.
vii) Current or prior auto-immune diseases per below: A. Moderate to severe rheumatoid arthritis. B. Auto-immune hepatitis or cholangitis. C. Myasthenia gravis. D. Moderate-to-severe or poorly controlled inflammatory bowel disease. E. Multiple sclerosis. F. Lupus with kidney involvement or moderate to severe lupus. G. Auto-immune myocarditis. Note: if participant meets Inclusion Criteria 5b or 5c, unknown PDL1 results per local SOC are acceptable in these specific cases.
* Patients with ER-low, HER2-negative BC must be ineligible, in the opinion of the Investigator, for endocrine therapy-based treatments.
* No previous systemic therapy in the locally advanced, recurrent inoperable or metastatic setting (ie incurable setting).
* Measurable disease by CT or MRI as per RECIST v1.1.
Exclusion Criteria
* Participants with a known germline breast cancer gene (BRCA) 1 or 2 mutation whose best 1L treatment option, in the opinion of the investigator, is a poli-ADP-ribose-polymerase inhibitors (PARPi).
* Untreated symptomatic central nervous system (CNS) metastases. Participants are eligible if CNS metastases have been treated, and participants' neurological signs and symptoms have returned to baseline. In addition, participants must have been either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization. Imaging performed within 28 days of randomization must document radiographic stability of CNS lesions and be performed after completion of any CNS directed therapy.
* Leptomeningeal metastases.
* Participants with history of severe heart disease including, but not limited to, any of the following:
i) History of clinically significant heart disease (eg, cardiomyopathy, congestive heart failure with New York Heart Association functional classification II to IV, pericarditis, or significant pericardial effusion).
ii) Myocardial infarction, uncontrolled angina, or stroke/transient ischemic attack within the past 6 months.
iii) QTc (by Fridericia's formula) prolongation ≥ 450 msec for males and ≥ 470 msec for females, except for right bundle branch block.
iv) Known LVEF \< 50%.
* Prior therapy with iza-bren or any other ADC targeting EGFR and/or HER3 or containing a topoisomerase 1 inhibitor payload.
* Other protocol-defined Inclusion/Exclusion criteria apply.
Primary outcome measure(s)
Progression-Free Survival (PFS) — Approximately 22 months from first participant randomization in Phase 3 Assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR)
Recommended Phase 3 Dose (RP3D) of BMS-986507 — Approximately 13 months from first participant randomization in Phase 2
Trial sites (295)
Facility
City
Region
Status
Local Institution - 0303
Hot Springs
Arkansas
Not Yet Recruiting
Helios Clinical Research
Cerritos
California
Recruiting
Local Institution - 0307
Cerritos
California
Withdrawn
Local Institution - 0308
Cerritos
California
Withdrawn
Local Institution - 0309
Cerritos
California
Withdrawn
Local Institution - 0311
Long Beach
California
Withdrawn
USC/Norris Comprehensive Cancer Center
Los Angeles
California
Recruiting
Valkyrie Clinical Trials
Los Angeles
California
Recruiting
USC Norris Oncology/Hematology-Newport Beach
Newport Beach
California
Recruiting
Local Institution - 0358
Stanford
California
Not Yet Recruiting
Local Institution - 0289
Aurora
Colorado
Not Yet Recruiting
Rocky Mountain Cancer Centers
Denver
Colorado
Recruiting
Medical Oncology Hematology Consultants, PA
Newark
Delaware
Recruiting
Local Institution - 0296
Pembroke Pines
Florida
Not Yet Recruiting
Local Institution - 0294
Atlanta
Georgia
Completed
Northside Hospital
Atlanta
Georgia
Recruiting
Local Institution - 0278
Chicago
Illinois
Withdrawn
Local Institution - 0280
Chicago
Illinois
Not Yet Recruiting
Decatur Memorial Hospital
Decatur
Illinois
Recruiting
Local Institution - 0324
O'Fallon
Illinois
Withdrawn
Ochsner Clinic Foundation
Covington
Louisiana
Recruiting
Local Institution - 1035
Baltimore
Maryland
Not Yet Recruiting
Massachusetts General Hospital
Boston
Massachusetts
Recruiting
Dana-Farber Cancer Institute
Boston
Massachusetts
Recruiting
Henry Ford Cancer- Detroit (Brigitte Harris Cancer Pavilion)
Detroit
Michigan
Recruiting
Minnesota Oncology Hematology
Maple Grove
Minnesota
Recruiting
Local Institution - 0372
Minneapolis
Minnesota
Not Yet Recruiting
Saint Luke's Cancer Institute
Kansas City
Missouri
Recruiting
Local Institution - 0312
New York
New York
Withdrawn
Memorial Sloan Kettering Cancer Center
New York
New York
Recruiting
Local Institution - 1037
Syracuse
New York
Not Yet Recruiting
Clinical Research Alliance
Westbury
New York
Recruiting
White Plains Hospital
White Plains
New York
Recruiting
Duke Cancer Institute
Durham
North Carolina
Recruiting
Willamette Valley Cancer Institute
Eugene
Oregon
Recruiting
Lehigh Valley Health Network
Allentown
Pennsylvania
Recruiting
Abramson Cancer Center of The University of Pennsylvania
Philadelphia
Pennsylvania
Recruiting
Local Institution - 0360
Pittsburgh
Pennsylvania
Not Yet Recruiting
St Francis Cancer Center
Greenville
South Carolina
Recruiting
Texas Oncology - Central/South Texas
Austin
Texas
Recruiting
+ 255 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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