This is a multicenter, multi-arm, biomarker-stratified trial designed to evaluate biomarker-directed therapies in patients with estrogen receptor-positive/hormone receptor-negative (ER+/HR-) and triple-negative (TN) metastatic breast cancer (MBC). The trial integrates both retrospective and prospective data collection, including archival tumor tissue, medical record abstraction, and prospective tumor and blood sampling prior to initiation of protocol directed treatment. Based on biomarker subtype, participants will receive standard of care therapy. Liquid biopsy will be collected on Cycle 2 Day 1, and then liquid biopsy, imaging and clinical data will be collected at each re-staging. Treatment will continue until discontinuation for progression, toxicity or at the discretion of the treating physician.
Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
Subject is willing and able to comply with study procedures based on the judgement of the investigator.
Age ≥ 18 years of age at the time of consent
ECOG Performance Status of 0-2 (see APPENDIX A: ECOG Performance Status Scale).
Inaccessible metastatic lesion to research biopsy
Subject has already initiated 2nd line therapy
Concurrent disease or condition that in the opinion of the treating oncologist renders the patient inappropriate for study participation
Parallel
SERD* + abemaciclib
DrugInvestigators choice Selective Estrogen Receptor Degrader + abemaciclib therapy.
SERD* + everolimus
DrugInvestigators choice Selective Estrogen Receptor Degrader + everolimus therapy.
SERD* + everolimus or capecitabine
DrugInvestigators choice Selective Estrogen Receptor Degrader + everolimus or capecitabine therapy.
SOC
Drugstandard-of-care (SOC) chemotherapy in breast cancer
Antiandrogen
DrugAntiandrogen therapy
6
Treatment groupsSee each treatment group below.
Intra-Individual Progression-Free Survival (PFS)
Progression-Free Survival (PFS) is defined as the time from initiation of study therapy until documented disease progression per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 or death from any cause, whichever occurs first. For intra-individual comparisons across successive therapy lines, a PFS ratio will be calculated by dividing the PFS of the current line (nth line, PFSₙ) by the PFS of the preceding line ((n-1)th line, PFSn-1). This allows each patient to serve as their own control, reducing between-patient variability and normalizing for the expected decline in PFS with later lines. RECIST v1.1 defines Complete Response (CR) as disappearance of all target lesions, Partial Response (PR) as ≥30% decrease, Stable Disease (SD) as insufficient change for PR or PD, and Progressive Disease (PD) as ≥20% increase, measurable growth in non-target lesions, or new lesions.
Progression free survival (PFS) - Between-Arm Evaluation
This endpoint assesses between two or more concurrently accruing arms, typically an investigational or biomarker-driven regimen versus a shared control or reference arm. Progression-Free Survival (PFS) is defined as the time from initiation of study therapy until documented disease progression per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 or death from any cause, whichever occurs first. RECIST v1.1 defines Complete Response (CR) as disappearance of all target lesions, Partial Response (PR) as ≥30% decrease, Stable Disease (SD) as insufficient change for PR or PD, and Progressive Disease (PD) as ≥20% increase, measurable growth in non-target lesions, or new lesions.
Tissue- and blood-based biomarkers on response rate
Tissue- and blood-based biomarkers predictive of response or resistance to standard-of-care first- and second-line therapies will be investigated. Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 will be used for tumor response assessment. RECIST v1.1 defines Complete Response (CR) as disappearance of all target lesions, Partial Response (PR) as ≥30% decrease, Stable Disease (SD) as insufficient change for PR or PD, and Progressive Disease (PD) as ≥20% increase, measurable growth in non-target lesions, or new lesions.
Overall survival (OS)
Overall survival (OS) is defined as the time from initiation of study therapy to death from any cause.
Objective response rate (ORR)
Objective response rate (ORR) is defined as the proportion of subjects with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. RECIST v1.1 defines Complete Response (CR) as disappearance of all target lesions, Partial Response (PR) as ≥30% decrease, Stable Disease (SD) as insufficient change for PR or PD, and Progressive Disease (PD) as ≥20% increase, measurable growth in non-target lesions, or new lesions.
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UNC Lineberger Comprehensive Cancer Center
Lead sponsor
Advanced Research Projects Agency for Health (ARPA-H)
Collaborator
Breast Cancer Research Foundation
Collaborator
Translational Breast Cancer Research Consortium
Collaborator
