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)

Bristol-Myers Squibb (BMS)

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Breast Neoplasms

Treatments: Drug: Paclitaxel; Drug: Iza-bren; Drug: Capecitabine; Drug: Gemcitabine; Drug: Nab-paclitaxel; Drug: Carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT06926868

2024-519871-24 (Other Identifier)

U1111-1316-1533 (Other Identifier)

CA244-0008

Details and patient eligibility

About

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.

Enrollment: 600 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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600 participants in 3 patient groups

Arm A1

Experimental group

Treatment:

Drug: Iza-bren

Arm A2

Experimental group

Treatment:

Drug: Iza-bren

Arm B

Active Comparator group

Treatment:

Drug: Carboplatin

Drug: Nab-paclitaxel

Drug: Gemcitabine

Drug: Capecitabine

Drug: Paclitaxel