UPCC 26125 A Randomized, Open-label, Inferentially Seamless Phase 2/3 Study of Izalontamab Brengitecan (BMS-986507) versus Treatment of Physician's Choice in Patients with Previously Untreated, Locally Advanced, Recurrent Inoperable, or Metastatic Triple negative Breast Cancer (TNBC) or ER-low, HER2-negative BC who are Ineligible for Anti-PD1/PD-L1 Treatment

Investigating an Investigational Medication for Advanced Triple Negative and Low Estrogen Receptor, HER2-negative Breast Cancer

Enrolling By Invitation
18 years or above
All
Phase 2/3
500 participants needed
1 Location

Brief description of study

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 of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Breast Neoplasms
  • Age: 18 years or above
  • Gender: All

Inclusion Criteria

  • Histologically or cytologically confirmed and documented locally-advanced, recurrent inoperable, or metastatic 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 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.
  • Patients with TNBC must be considered ineligible for 1L chemotherapy combination treatment with an anti-PD-1 or an anti-PD-L1 due to either 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 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.
  • 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.
  • Other protocol-defined Inclusion/Exclusion criteria apply.

This study investigates the effectiveness and safety of an investigational medication, a bi-specific antibody-drug conjugate, for patients with advanced triple-negative breast cancer (TNBC) or ER-low, HER2-negative breast cancer (BC). These patients have not received prior treatment for their condition and are not eligible for certain standard therapies. The investigational medication targets specific proteins, EGFR and HER3, and includes a topoisomerase inhibitor, which is a type of drug that interferes with cancer cell growth.

Participants in the study will be randomly assigned to receive either the investigational medication or a treatment chosen by their physician from a list of standard options. These options include various chemotherapy drugs. The study will involve regular monitoring of the participants' health and response to treatment using imaging techniques like CT or MRI scans, following specific criteria to measure disease progression.

  • Who can participate: Adults with advanced TNBC or ER-low, HER2-negative BC who have not received prior systemic therapy for their condition may participate. Key eligibility includes confirmed diagnosis based on specific criteria and ineligibility for certain standard therapies.
  • Study details: Participants will receive either the investigational medication or a standard treatment chosen by their doctor. Regular health monitoring and imaging tests will be conducted to assess treatment effects.
Updated on 10 Jun 2026. Study ID: 25-1672
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