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)

Phase 2

Recruiting

• Conditions: Breast Neoplasms
• Interventions: Drug: Iza-bren; Drug: Nab-paclitaxel; Drug: Paclitaxel; Drug: Capecitabine; Drug: Carboplatin; Drug: Gemcitabine

• Registration Number: NCT06926868
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-04-08
• Study First Submitted QC: 2025-04-08
• Study First Posted: 2025-04-15
• Status Verified: 2025-07
• Study Start: 2025-07-15
• Last Update Submitted: 2025-07-15
• Last Update Posted: 2025-07-17
• Primary Completion: 2028-03-13
• Study Completion: 2030-05-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 560

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 FISH 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 FISH 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:.
• Investigator-determined ineligibility based on PD-L1 negative disease determined and documented prior to trial screening as part of SoC.
• Has experienced disease relapse between 6 to 12 months after the completion of (neo)adjuvant therapy with an anti-PD(L)1.
• 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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A1	Iza-bren	-
Arm A2	Iza-bren	-
Arm B	Nab-paclitaxel	-
Arm B	Paclitaxel	-
Arm B	Capecitabine	-
Arm B	Carboplatin	-
Arm B	Gemcitabine	-

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	Approximately 31 months from first participant randomization	Assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR)

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Approximately up to 57 months from first participant randomization
Recommended Phase 3 Dose (RP3D) of BMS-986507	Approximately 19 months from first participant randomization
Number of participants with treatment-related Adverse Events (AEs)	Approximately up to 57 months from first participant randomization
Number of participants with laboratory abnormalities	Approximately up to 57 months from first participant randomization
Number of participants with serious AEs (SAEs)	Approximately up to 57 months from first participant randomization
Number of participants with AEs leading to treatment discontinuation, interruption, dose reduction or dose delay	Approximately up to 57 months from first participant randomization
Number of deaths	Approximately up to 57 months from first participant randomization
Objective Response (OR)	Approximately 31 months from first participant randomization
PFS rate	Approximately 31 months from first participant randomization	Assessed using RECIST v1.1 by BICR
PFS	Approximately 31 months from first participant randomization	Assessed by Investigator
Disease control rate (DCR)	Approximately 31 months from first participant randomization
Duration of Response (DOR)	Approximately 31 months from first participant randomization
Time to Response (TTR)	Approximately 31 months from first participant randomization
Time to subsequent treatment (TTST)	Approximately up to 57 months from first participant randomization	Defined as time from randomization to the start of subsequent therapy or death
Progression-free survival after next line of treatment (PFS2)	Approximately up to 57 months from first participant randomization	Defined as the time from randomization to the date of investigator-defined documented disease progression after next line of treatment or death due to any cause, whichever comes first
Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)	Approximately up to 57 months from first participant randomization
Change from baseline in EORTC Breast Cancer-specific Quality of Life Questionnaire (QLQ-BR23)	Approximately up to 57 months from first participant randomization
Functional Assessment of Chronic Illness Therapy item GP5 (FACIT GP5) score	Approximately up to 57 months from first participant randomization
Change from baseline in European Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L)	Approximately up to 57 months from first participant randomization

Trial Locations

Locations (238)

Local Institution - 0303; 🇺🇸 Hot Springs, Arkansas, United States

Local Institution - 0307; 🇺🇸 Cerritos, California, United States

Local Institution - 0308; 🇺🇸 Cerritos, California, United States

Local Institution - 0309; 🇺🇸 Cerritos, California, United States

Local Institution - 0311; 🇺🇸 Long Beach, California, United States

Local Institution - 0290; 🇺🇸 Los Angeles, California, United States

Local Institution - 0283; 🇺🇸 Los Angeles, California, United States

Local Institution - 0328; 🇺🇸 Whittier, California, United States

Local Institution - 0289; 🇺🇸 Aurora, Colorado, United States

Local Institution - 0304; 🇺🇸 Newark, Delaware, United States

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