An Open-label, Interventional, Multicenter, Randomized, Phase 2 Study of Fulvestrant With or Without Samuraciclib in Participants With Metastatic or Locally Advanced Hormone Receptor (HR) Positive and Human Epidermal Growth Factor Receptor (HER)2-Negative Breast Cancer (BC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 32
- 主要终点
- Clinical Benefit Response (CBR)
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of samuraciclib in combination with fulvestrant versus fulvestrant alone in adult participants with metastatic or locally advanced Hormone Receptor (HR) positive and Human Epidermal Growth Factor Receptor (HER)2-negative breast cancer.
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
- •Histologically confirmed diagnosis of ER-positive, HER2-negative locally advanced or metastatic breast cancer.
- •Documented objective disease progression while on or within 6 months after the end of the most recent therapy.
- •Received prior AI in combination with a CDK4/6i as the last therapy
- •Known TP53 mutation status.
- •Participants must have measurable disease or bone only disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.
- •Pre/peri-menopausal participants must have commenced treatment with a luteinizing hormone-releasing hormone (LHRH) agonist at least 4 weeks prior to first dose of study intervention.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1 with no deterioration over the past 2 weeks.
- •Expected life expectancy of >12 weeks in the judgement of the treating investigator.
排除标准
- •Inflammatory breast cancer.
- •Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
- •More than 1 line of endocrine treatment for locally advanced or metastatic disease treatment.
- •Inadequate hepatic, renal, and bone marrow function.
- •Clinically significant cardiovascular disease.
- •Any current or prior central nervous system metastases, carcinomatous meningitis, or leptomeningeal disease.
- •Pregnant or breastfeeding women.
研究组 & 干预措施
Arm A
Participants will receive 360 mg of samuraciclib on cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onwards in combination with fulvestrant administered monthly, plus an additional dose at Cycle 1 Day 15.
干预措施: Samuraciclib (Drug)
Arm A
Participants will receive 360 mg of samuraciclib on cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onwards in combination with fulvestrant administered monthly, plus an additional dose at Cycle 1 Day 15.
干预措施: Fulvestrant (Drug)
Arm B
Participants will receive 240 mg of samuraciclib on cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onwards in combination with fulvestrant administered monthly, plus an additional dose at Cycle 1 Day 15.
干预措施: Samuraciclib (Drug)
Arm B
Participants will receive 240 mg of samuraciclib on cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onwards in combination with fulvestrant administered monthly, plus an additional dose at Cycle 1 Day 15.
干预措施: Fulvestrant (Drug)
Arm C
Participants will receive fulvestrant administered monthly, plus additional dose at Cycle 1 Day 15.
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Clinical Benefit Response (CBR)
时间窗: From randomization until Week 24
CBR is defined as the overall complete response (CR), partial response (PR), or stable disease (SD) ≥ 24 weeks according to RECIST version 1.1 recorded from randomization until disease progression, or death due to any cause.
次要结局
- Progression Free Survival (PFS)(Time from the date of first dose of study intervention until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48))
- Incidence and severity of adverse events (AEs) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0(From first dose of any study intervention through 28 days after the last dose of any study intervention)
- Samuraciclib plasma exposure: Ctrough(Cycle 1 Days 8 and 15; Day 1 of Cycles 2, 3, 4, 5, and 6; and within 28 days of last dose (each cycle is 28 days))
- Duration of Response (DOR)(Time from the date of first dose of study intervention until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48))
- Fulvestrant plasma exposure: Ctrough(Cycle 1 Days 8 and 15; Day 1 of Cycles 2, 3, 4, 5 and 6; and within 28 days of last dose (each cycle is 28 days))
- Objective Response Rate (ORR)(Time from the date of first dose of study intervention until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48))
- Samuraciclib plasma exposure: Cmax(Day 1 of Cycles 2 and 3 (each cycle is 28 days))