Izalontamab brengitecan versus chemotherapy for first-line metastatic triple-negative or ER-low, HER2-negative breast cancer in patients not eligible for anti-PD(L)1 drugs

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 2/3 interventional trial compares iza-bren, a bi‑specific ADC targeting EGFR and HER3 with a topoisomerase inhibitor payload, against physician's choice chemotherapy (paclitaxel, nab‑paclitaxel, carboplatin plus gemcitabine, or capecitabine) as first-line therapy. Eligible participants are adults with locally advanced, recurrent inoperable, or metastatic triple‑negative breast cancer or ER‑low, HER2‑negative disease who are not candidates for anti‑PD(L)1 therapy. Participants will be assigned to receive iza-bren or one of the standard chemotherapy options and followed for tumor response, progression, and treatment-related safety outcomes. The study aims to determine whether iza-bren can improve outcomes compared with standard chemotherapy in this specific patient population.

Why it matters

Who can join: the full rules

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.

Where it's running

• Helios Clinical Research
  Cerritos, California, United States Recruiting
• USC/Norris Comprehensive Cancer Center
  Los Angeles, California, United States Recruiting
• Valkyrie Clinical Trials
  Los Angeles, California, United States Recruiting
• USC Norris Oncology/Hematology-Newport Beach
  Newport Beach, California, United States Recruiting
• Rocky Mountain Cancer Centers
  Denver, Colorado, United States Recruiting
• Medical Oncology Hematology Consultants, PA
  Newark, Delaware, United States Recruiting

+245 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: BMS Clinical Trials Contact Center www.BMSClinicalTrials.com
• Email: Clinical.Trials@bms.com
• Phone: 855-907-3286

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Improved Facial Skin Quality After VYC-12L for Breast Cancer Survivors

  This study tests whether intradermal injections of VYC-12L can improve facial skin quality and quality of life in adults who have completed breast cancer treatment.

  Recruiting Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia · Murcia, Murcia · NCT07917117

• Breast cancer subtypes and outcomes in Colombian women

  This study looks back at medical records of women with breast cancer to see how different molecular subtypes relate to survival and recurrence in a single Colombian hospital.

  Recruiting Fundación Santa Fe de Bogota · Bogotá, Bogota D.C. · NCT07856225

• Multimodal psychosomatic symptom care for breast cancer: personalized acupuncture care guided by shared decision-making

  This study tests whether personalized acupuncture options (manual acupuncture, ear acupuncture, or both) can help women with breast cancer who have anxiety, sleep problems, or fatigue, compared to routine nursing care.

  Recruiting at 3 sites First Teaching Hospital of Tianjin University of Traditional Chinese Medicine · Tianjin and 2 other locations · NCT07763587

• Slow Jogging for Breast Cancer Survivors

  This study tests whether a 12-week slow jogging program helps sleep quality in women who have completed breast cancer treatment.

  Recruiting Mackay Memorial Hospital · Taipei, Taipei City · NCT07757763

• Methylscape test in body fluids for multi-cancer detection in Colombia

  A simple blood, urine, or saliva test called Methylscape is being tested to see if it can detect multiple cancers and identify where the signal is coming from, using people with cancer and healthy volunteers in Colombia.

  Recruiting Centro de Tratamiento e Investigación sobre Cáncer, Luis Carlos Sarmiento Angulo · Bogotá, Bogota D.C. · NCT07741435

• Benchmarking AI language models against tumor boards for oncology treatment decisions

  This project tests whether frontier AI language models can match the treatment recommendations of multidisciplinary tumor boards for common cancers using standardized synthetic cases.

  Recruiting Assistance Publique - Hôpitaux de Paris · Boulogne-Billancourt and 4 other locations · NCT07739121

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.