Health Condition 1: C509- Malignant neoplasm of breast of unspecified site
Conditions
Interventions
Intervention1: izalontamab brengitecan: 2.0 or 2.5 mg/kg on Days 1 and 8 of each 21-day cycle/IV infusion
Control Intervention1: Nab-paclitaxel: 100 mg/m2 on Days 1, 8, and 15 of each 28-day cycle/IV
Sponsors
BRISTOL MYERS SQUIBB INDIA PRIVATE LIMITED
Eligibility
Inclusion criteria
Inclusion criteria: 1) Participants must have signed and dated an IRB/IEC-approved written ICF in accordance with regulatory, local, and institutional guidelines. This ICF must be obtained before performing any protocol-related procedures that are not part of normal patient care. Note: Participants must agree to comply with the requirements and restrictions listed in the ICF and in this protocol. Females or males must be able to understand and give written informed consent. Type of Participant and Target Disease Characteristics 2) Histologically or cytologically confirmed and documented locally-advanced, recurrent inoperable, or metastatic TNBC (ER and PgR less than 1 percentage, 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 percentage, 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 another pathology specimen. - Participants diagnosed with HR+ or HER2+ BC synchronically are not allowed, whereas patients diagnosed with and treated for HR+ or HER2+ BC in the early setting must have locally confirmed TNBC or ER-low, HER2-negative BC with a biopsy obtained from a local recurrence or distant metastasis site. - De novo metastatic disease presentation is allowed if anthracyclines are contraindicated or not considered the best treatment option in the opinion of the treating physician. 3) Submission of a recent tumor tissue biopsy collected within 6 months is required at the time of randomization. Archival sample collected within less than 5 years and obtained before the diagnosis of locally unresectable or metastatic may be submitted only in cases where a recent biopsy is not available. Tumor tissue as one FFPE block (preferred) or a minimum of 15 unstained slides sectioned within 3 months are acceptable. If, despite best efforts, a minimum of 15 slides are not obtainable, submission of fewer slides may be acceptable following discussion with the Medical Monitor. For participants in China, refer to APPENDIX 8. 4) Participants with recurrent disease must have experienced disease relapse at least 6 months after finishing their last therapy with curative intent (eg, at least 6 months after the last dose of [neo]adjuvant chemotherapy, breast surgery, or the last dose of adjuvant therapy [eg, pembrolizumab, capecitabine, olaparib], whichever is the latest; prior use of adjuvant endocrine therapy-based treatments does not factor in). - The inclusion of participants relapsing between 6 to 12 months after finishing their last treatment with curative intent will be capped at approximately 20 percentage of the total planned sample size, after which only those relapsing after 12 months or those presenting with de novo metastatic disease will be included. 5) 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 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, in the opinion of the investigat
Exclusion criteria
Exclusion criteria: 1) Participants with a known germline BRCA 1 or 2 mutation whose best 1L treatment option, in the opinion of the investigator, is a PARPi. 2) 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 less than or equal too 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. 3) Leptomeningeal metastases. 4) Active viral hepatitis, including the following: - Any positive test result for HBV indicating presence of virus, eg, HBV DNA positive would be excluded. Participants with anti-HBs positive in line with prior vaccination are eligible to enroll. - Any positive test result for HCV indicating presence of active viral replication (detectable HCV-RNA). - Participants with positive HCV antibody and an undetectable HCV RNA are eligible to enroll. 5) Other clinically active infectious liver disease including co-infection with hepatitis B and C/D (either known or detected reflexively in a patient with stable HBV infection). 6) Known HIV infection. Patients are allowed to participate if all of the following criteria are met - Undetectable HIV RNA and CD4 count greater than or equal too 350 cells per microliter at the time of screening. - No AIDS-defining opportunistic infection within 12 months prior to screening. - On ART for at least 4 weeks prior to enrollment with projected continuation of ART as clinically indicated while on the study. Note: Testing for HIV must be performed at sites where mandated locally. HIV-positive participants must be excluded where mandated locally. 7) Participants with history of severe heart disease including, but not limited to, any of the following: - 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). - Myocardial infarction, uncontrolled angina, or stroke/transient ischemic attack within the past 6 months. - QTcF prolongation greater than 470 msec, except for right bundle branch block. 8) Participants with known bleeding coagulation disorders, including but not limited to hemophilia, von Willebrand disease, or any other coagulopathies that may affect blood clotting. 9) Participants with known hematologic conditions that may affect bone marrow reserve, including but not limited to myelodysplastic syndrome, pre-malignant clonal states (clonal hematopoiesis of indeterminate potential, clonal cytopenia of unknown significance, idiopathic cytopenia of undetermined significance, idiopathic dysplasia of unknown significance), unexplained anemia, unexplained thrombocytopenia, and a history of immune thrombocytopenia. 10) Participants with prior malignancies, except: - Non-melanoma skin cancer or carcinoma in situ of the cervix or carcinoma in situ of the prostate. - Other malignancies with a disease-free interval of at least 3 years. 11) Participants with
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PFS per BICRTimepoint: Approximately 31 months from first participant randomization | — |
Secondary
| Measure | Time frame |
|---|---|
| 1.RP3D, PFS rate, Tumour size change 2.OR, PFS, DCR, DOR, TTR, ORR (RECIST version 1.1) 3.OS, AEs, Lab abnormalities, SAEs, AEs leading to dose change or discontinuation, Deaths, TTST, PFS2, EORTC QL C30, QLQ BR23, FACIT GP5, EQ 5D 5LTimepoint: 1.Up to 19 month 2.31 month 3.Up to 57 month | — |
Countries
Argentina, Australia, Austria, Canada, Chile, China, Colombia, Democratic People's Republic of Korea, France, Germany, India, Israel, Italy, Japan, Mexico, Poland, Portugal, Singapore, South Africa, Spain, Sweden, Switzerland, Turkey, United Arab Emirates, United Kingdom, United States of America
Contacts
Public ContactShilpi Sinha
Bristol-Myers Squibb India Pvt. Ltd.
Outcome results
None listed