Breast Neoplasms
Conditions
Keywords
triple-negative breast cancer, antibody-drug conjugate, ER-low/HER2-negative breast cancer
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.
Interventions
DRUGIza-bren
Specified dose on specified days
DRUGNab-paclitaxel
Specified dose on specified days
DRUGPaclitaxel
Specified dose on specified days
DRUGCapecitabine
Specified dose on specified days
DRUGCarboplatin
Specified dose on specified days
DRUGGemcitabine
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
SystImmune Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Approximately up to 47 months from first participant randomization in Phase 3 | — |
| Number of participants with treatment-related Adverse Events (AEs) | Approximately up to 47 months from first participant randomization in Phase 3 | — |
| Number of participants with laboratory abnormalities | Approximately up to 47 months from first participant randomization in Phase 3 | — |
| Number of participants with serious AEs (SAEs) | Approximately up to 47 months from first participant randomization in Phase 3 | — |
| Number of participants with AEs leading to treatment discontinuation, interruption, dose reduction or dose delay | Approximately up to 47 months from first participant randomization in Phase 3 | — |
| Number of deaths | Approximately up to 47 months from first participant randomization in Phase 3 | — |
| Objective Response (OR) per BICR | Approximately 22 months from first participant randomization in Phase 3 | — |
| Objective Response (OR) per Investigator | Approximately 22 months from first participant randomization in Phase 3 | — |
| PFS rate | 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 BICR |
| Relative change in tumor size | Approximately 22 months from first participant randomization in Phase 3 | — |
| Disease control rate (DCR) per BICR | Approximately 22 months from first participant randomization in Phase 3 | — |
| Disease control rate (DCR) per Investigator | Approximately 22 months from first participant randomization in Phase 3 | — |
| PFS | Approximately 22 months from first participant randomization in Phase 3 | Assessed by Investigator |
| Duration of Response (DOR) per BICR | Approximately 22 months from first participant randomization in Phase 3 | — |
| Duration of response (DOR) per Investigator | Approximately 22 months from first participant randomization in Phase 3 | — |
| Time to Response (TTR) per BICR | Approximately 22 months from first participant randomization in Phase 3 | — |
| Time to response (TTR) per Investigator | Approximately 22 months from first participant randomization in Phase 3 | — |
| Time to subsequent treatment (TTST) per Investigator | Approximately up to 47 months from first participant randomization in Phase 3 | 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 47 months from first participant randomization in Phase 3 | 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 47 months from first participant randomization in Phase 3 | — |
| Change from baseline in EORTC Breast Cancer-specific Quality of Life Questionnaire (QLQ-BR23) | Approximately up to 47 months from first participant randomization in Phase 3 | — |
| Functional Assessment of Chronic Illness Therapy item GP5 (FACIT GP5) score | Approximately up to 47 months from first participant randomization in Phase 3 | — |
| Change from baseline in European Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L) | Approximately up to 47 months from first participant randomization in Phase 3 | — |
Countries
Argentina, Australia, Austria, Brazil, Canada, Chile, China, Colombia, France, Germany, Greece, India, Israel, Italy, Japan, Mexico, Poland, Portugal, Romania, South Africa, South Korea, Spain, Sweden, Switzerland, Turkey (Türkiye), United Arab Emirates, United Kingdom, United States
Contacts
CONTACTBMS Clinical Trials Contact Center www.BMSClinicalTrials.com
CONTACTFirst line of the email MUST contain NCT # and Site #.
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed