A Phase 1b/2 Open-label Study of Samuraciclib in Combination With Elacestrant in Participants With Metastatic or Locally Advanced Hormone Receptor-positive and Human Epidermal Growth Factor Receptor 2-negative Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 23
- 主要终点
- Phase 2 (Expansion)
研究概览
简要总结
This is an international, multisite, open-label, Phase 1b/2 study, to confirm safety and efficacy of samuraciclib in combination with elacestrant in adult participants with metastatic or locally advanced Hormone Receptor (HR) positive and Human Epidermal Growth Factor Receptor (HER)2-negative breast cancer.
详细描述
This is a multiple cohort study, an initial dose escalation phase is designed to confirm the safe dose of samuraciclib in combination with elacestrant. A Safety Review Committee (SRC) will monitor the safety, tolerability, and PK data during this phase. Once ascertained, an expansion cohort will be opened to explore the efficacy of samuraciclib in combination with elacestrant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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 and ESR1 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
Cohort 1
Up to 6 evaluable participants will receive samuraciclib 240 mg in combination with elacestrant 300 mg in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onwards).
干预措施: Samuraciclib (Drug)
Cohort 1
Up to 6 evaluable participants will receive samuraciclib 240 mg in combination with elacestrant 300 mg in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onwards).
干预措施: Elacestrant Dihydrochloride (Drug)
Cohort 2
Up to 6 evaluable participants will receive samuraciclib in combination with elacestrant at the SRC recommended dose (anticipated 360mg samuraciclib, 300 mg elacestrant) in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onward).
干预措施: Samuraciclib (Drug)
Cohort 2
Up to 6 evaluable participants will receive samuraciclib in combination with elacestrant at the SRC recommended dose (anticipated 360mg samuraciclib, 300 mg elacestrant) in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onward).
干预措施: Elacestrant Dihydrochloride (Drug)
Cohort 3
Up to 6 evaluable participants will receive samuraciclib in combination with elacestrant at the SRC recommended dose (anticipated 360mg samuraciclib, 400 mg elacestrant) in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onward).
干预措施: Samuraciclib (Drug)
Cohort 3
Up to 6 evaluable participants will receive samuraciclib in combination with elacestrant at the SRC recommended dose (anticipated 360mg samuraciclib, 400 mg elacestrant) in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onward).
干预措施: Elacestrant Dihydrochloride (Drug)
Cohort 4 Expansion
Up to 30 evaluable participants will receive samuraciclib in combination with elacestrant at the SRC recommended dose (anticipated 360mg samuraciclib, 400 mg elacestrant) in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onward).
干预措施: Samuraciclib (Drug)
Cohort 4 Expansion
Up to 30 evaluable participants will receive samuraciclib in combination with elacestrant at the SRC recommended dose (anticipated 360mg samuraciclib, 400 mg elacestrant) in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onward).
干预措施: Elacestrant Dihydrochloride (Drug)
结局指标
主要结局
Phase 2 (Expansion)
时间窗: From the date of first dose of any study intervention (Cycle 1 Day 1) until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48)
Progression Free Survival (PFS) is defined as the time from the date of first dose of IMP (Cycle 1 Day 1) to the date of the first documentation of objective progressive disease (PD) or death due to any cause, whichever occurs first.
Phase 1b (Dose-finding)
时间窗: From the date of first dose of any study intervention (Day 1 Cycle 1) and through 28 days after the last dose of any study intervention
Identification of Samuraciclib + Elacestrant combination, Phase 2, expansion dose level. Incidence and severity of adverse events as graded by the National Cancer Institute Common Terminology Criteria for Adverse events (NCI-CTCAE) v5.0. Safety will be assessed by monitoring treatment - emerged severe and dose limiting adverse events and clinically relevant changes in vital signs and clinical laboratory results
次要结局
- Treatment-Emergent Adverse Events and Laboratory Abnormalities (Safety and Tolerability)(From the date of first dose of any study intervention through 28 days after the last dose of any study intervention)
- Overall response rate (ORR)(the date of first dose of study intervention (Cycle 1 Day 1) until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48))
- Elacestrant exposure: Cmax(Day 1 of Cycles 1 and Cycle 2 (each cycle is 28 days))
- Clinical Benefit Response (CBR)(From the date of first dose of any study intervention (Cycle 1 Day 1) to ≥ 24 weeks or until disease progression or death to any cause (assessed up to week 24))
- Best percent change in tumor size.(From the date of first dose of study intervention (Cycle 1 Day 1) 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 1 and Cycle 2 (each cycle is 28 days))
- Genotyping for ESR1 and TP53 mutations(Screening)
- Duration of Response (DOR)(From the date of first dose of study intervention (Cycle 1 Day 1) 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: Ctrough(Cycle 1 Day 2 and 15; Day 2 of Cycle 2; Day 1 of Cycles 3-6 and end of treatment within 28 days of last dose of IMP and prior to the initiation of a new anticancer therapy (each cycle is 28 days)])
- Elacestrant exposure: Ctrough(Cycle 1 Day 2 and Day 15; Cycle 2 Day 2 of Cycle 2 and Day 1 of Cycles 3-6 and at end of treatment within 28 days of the last dose of IMP and prior to the initiation of a new anticancer therapy (each cycle is 28 days))