A Phase III Randomized, Open-Label Study Evaluating Efficacy and Safety of Giredestrant Compared With Fulvestrant, Both Combined With a CDK4/6 Inhibitor, in Patients With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer With Resistance to Prior Adjuvant Endocrine Therapy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,050
- 试验地点
- 1,153
- 主要终点
- Progression-Free Survival (PFS) in the ESR1 mutation (ESR1m) Subgroup
研究概览
简要总结
This is a Phase III, randomized, open-label multicenter study that will evaluate the efficacy and safety of giredestrant compared with fulvestrant, both in combination with the investigator's choice of a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib), in participants with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer who have developed resistance to adjuvant endocrine therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Locally advanced or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
- •Documented estrogen receptor-positive (ER+), HER2-negative (HER2-) tumor assessed locally on the most recent tumor biopsy (or an archived tumor sample if a recent tumor sample is not available for testing)
- •Confirmed ESR1 mutation status (ESR1m versus ESR1nmd) in baseline circulating tumor DNA (ctDNA) through central laboratory testing
- •Resistance to prior adjuvant endocrine therapy (ET), which is defined as having relapsed with prior standard adjuvant ET, on-treatment after >/=12 months or off-treatment within 12 months of completion. Prior use of adjuvant CDK4/6i is allowed (if relapse occurred >/=12 months since completion).
- •No prior systemic anti-cancer therapy for advanced disease
- •Measurable disease as defined per RECIST v.1.1 or non-measurable (including bone-only) disease
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1
- •For pre/perimenopausal women and for men: willing to undergo and maintain treatment with approved LHRH agonist therapy (as per local guidelines) for the duration of study treatment
排除标准
- •Prior systemic therapy (e.g., prior chemotherapy, immunotherapy, or biologic therapy) for locally advanced unresectable or metastatic breast cancer
- •Prior treatment with another SERD (e.g., fulvestrant, oral SERDs) or novel ER-targeting agents
- •Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
- •Active cardiac disease or history of cardiac dysfunction
- •Clinically significant history of liver disease
研究组 & 干预措施
Fulvestrant + Investigator's Choice of CDK4/6i
Participants in the control arm will receive fulvestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
干预措施: LHRH Agonist (Drug)
Fulvestrant + Investigator's Choice of CDK4/6i
Participants in the control arm will receive fulvestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
干预措施: Ribociclib (Drug)
Fulvestrant + Investigator's Choice of CDK4/6i
Participants in the control arm will receive fulvestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
干预措施: FoundationOne Liquid CDx Assay (F1LCDx) (Diagnostic Test)
Giredestrant + Investigator's Choice of CDK4/6i
Participants in the experimental arm will receive giredestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
干预措施: LHRH Agonist (Drug)
Giredestrant + Investigator's Choice of CDK4/6i
Participants in the experimental arm will receive giredestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
干预措施: FoundationOne Liquid CDx Assay (F1LCDx) (Diagnostic Test)
Giredestrant + Investigator's Choice of CDK4/6i
Participants in the experimental arm will receive giredestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
干预措施: Abemaciclib (Drug)
Giredestrant + Investigator's Choice of CDK4/6i
Participants in the experimental arm will receive giredestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
干预措施: Giredestrant (Drug)
Giredestrant + Investigator's Choice of CDK4/6i
Participants in the experimental arm will receive giredestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
干预措施: Palbociclib (Drug)
Giredestrant + Investigator's Choice of CDK4/6i
Participants in the experimental arm will receive giredestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
干预措施: Ribociclib (Drug)
Fulvestrant + Investigator's Choice of CDK4/6i
Participants in the control arm will receive fulvestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
干预措施: Abemaciclib (Drug)
Fulvestrant + Investigator's Choice of CDK4/6i
Participants in the control arm will receive fulvestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
干预措施: Palbociclib (Drug)
Fulvestrant + Investigator's Choice of CDK4/6i
Participants in the control arm will receive fulvestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) in the ESR1 mutation (ESR1m) Subgroup
时间窗: From randomization to first occurrence of progressive disease (PD) or death (up to 5 years)
PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), or death from any cause during the study.
PFS in the Full Analysis Set (FAS) Population
时间窗: From randomization to first occurrence of PD or death (up to 5 years)
次要结局
- Time to Confirmed Deterioration (TTCD) in Pain Severity(From randomization until end of follow-up (up to 5 years))
- Duration of Response (DOR)(From the first occurrence of a documented objective response to PD or death (up to 5 years))
- Incidence and Severity of Adverse Events(From Baseline until 28 days after the final dose of study treatment (up to 5 years))
- Number of Participants with Clinical Laboratory Test Abnormalities for Hematology and Biochemistry Parameters Over the Course of the Study(From Baseline until 28 days after the final dose of study treatment (up to 5 years))
- Confirmed Objective Response Rate (cORR)(From randomization until treatment discontinuation (up to 5 years))
- Clinical Benefit Rate (CBR)(From randomization until treatment discontinuation (up to 5 years))
- Time to Chemotherapy(From randomization until the start of chemotherapy or death (up to 5 years))
- TTCD in Pain Presence and Interference(From randomization until end of follow-up (up to 5 years))
- TTCD in Role Functioning(From randomization until end of follow-up (up to 5 years))
- Number of Participants with Vital Sign Abnormalities Over the Course of the Study(From Baseline until 28 days after the final dose of study treatment (up to 5 years))
- PFS in the ESR1 no-mutation-detected (ESR1nmd) Subgroup(From randomization to first occurrence of PD or death (up to 5 years))
- Overall Survival (OS)(From randomization until death from any cause (up to 5 years))
- TTCD in Physical Functioning(From randomization until end of follow-up (up to 5 years))
- TTCD in Global Health Status/Quality of Life(From randomization until end of follow-up (up to 5 years))