TBCRC Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies (EVOLVE-BDT)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 700
- 试验地点
- 6
- 主要终点
- Intra-Individual Progression-Free Survival (PFS)
研究概览
简要总结
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.
详细描述
The platform design makes it easy to assess multiple targeted therapies at the same time, focusing on patient groups identified by specific biomarkers. Patients who experience disease progression may be reassigned to additional eligible sub trials evaluating alternative therapeutic options. The primary endpoint for each arm is progression-free survival (PFS). This adaptive framework enables continuous learning and rapid translation of biomarker discoveries into therapeutic evaluation, promoting an agile and data-driven approach to treatment optimization in advanced breast cancer.
Beyond ER and HER2, there are few biomarkers to drive treatment decisions in metastatic and primary breast cancer, leaving a gap in effective treatments for other subtypes. To address this, triple-negative (TNBC) is pioneering an adaptive, evolutionary trial focusing on women with metastatic breast cancer (MBC) in the second-line (2L) setting. The adaptive trial infrastructure is designed to serve as an integrated parent study, enabling coordinated acquisition of clinical and translational data, as well as training and testing activities. Within this framework, individual biomarker-driven sub-trials (based on biomarker development) can be created and conducted.
Eligible participants include patients with ER+/HER2- or triple-negative (TNBC) metastatic breast cancer (MBC) who have progressed on first line (1L) therapy but have not yet initiated second-line (2L) treatment. HER2+ patients will be excluded due to the availability of established effective therapies.
This Sub Protocol #1 will enroll subjects based on biomarker subtype. Participants will receive a 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. In order to participate in Sub Protocol #1 subjects must have consented to the Parent protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
- •Patients must fulfill all eligibility criteria outlined in the LCCC2521 Parent Protocol and consented to LCCC2521 Parent Protocol
排除标准
- •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
研究组 & 干预措施
Cohort 1- Arm B
ER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant positive or negative and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion negative.
干预措施: SERD* + everolimus (Drug)
Cohort 2 Arm A
ER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant negative or positive, and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion positive.
干预措施: SERD* + abemaciclib (Drug)
Cohort 1 Arm A
ER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant positive or negative and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion negative.
干预措施: SERD* + abemaciclib (Drug)
Cohort 2 Arm B
ER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant negative or positive, and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion positive.
干预措施: SERD* + everolimus or capecitabine (Drug)
Cohort 3
Triple-Negative Breast Cancer (TNBC): ER- (Estrogen receptor negative), PR- (Progesterone receptor negative), HER2- HER2 negative. AR - = Androgen Receptor negative, PD-L1 (Programmed Death-Ligand 1) positive or negative.
干预措施: SOC (Drug)
Cohort 4
Triple-Negative Breast Cancer (TNBC): ER- (Estrogen receptor negative), PR- (Progesterone receptor negative), HER2- HER2 negative. AR + = Androgen Receptor positive, PD-L1 (Programmed Death-Ligand 1) positive or negative.
干预措施: Antiandrogen (Drug)
结局指标
主要结局
Intra-Individual Progression-Free Survival (PFS)
时间窗: Up to 5 years
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.
次要结局
- Progression free survival (PFS) - Between-Arm Evaluation(Up to 3 months)
- Tissue- and blood-based biomarkers on response rate(Up to 3 months)
- Overall survival (OS)(Up to 12 months)
- Objective response rate (ORR)(Up to 3 months)
- Duration of response (DoR)(Up to 12 months)
- Clinical benefit rate (CBR)(Up to 12 months)
- Grade 2 or above Adverse Events per NCI Common Terminology Criteria for Adverse Events (CTCAE)(Up to 12 months)
- Changes in circulating tumor DNA (ctDNA) levels(Up to 12 months)
- Changes in transcriptomic data - tissue(Up to 12 months)
- Changes in transcriptomic data - blood(Up to 12 months)
- Changes in Circulating tumor DNA (ctDNA) and tumor response relation(Up to 12 months)
- Progression free survival (PFS) -Within Arm Evaluation(Up to 5 years)