A Phase I/Ib, Open Label Study of LSZ102 Single Agent and LSZ102 in Combination With Either LEE011 (LSZ102 + LEE011) or BYL719 (LSZ102 + BYL719) in Patients With Advanced or Metastatic ER+ Breast Cancer Who Have Progressed After Endocrine Therapy
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 199
- 试验地点
- 4
- 主要终点
- Safety and tolerability of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719
研究概览
简要总结
To characterize the safety and tolerability, identify recommended doses and regimens for future studies, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of LSZ102 as a single agent and in combination with either LEE011 or BYL719 in adult patients with locally advanced or metastatic ER+ breast cancer who have progressed after endocrine therapy.
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 must be obtained prior to any procedures
- •Histologically and/or cytologically confirmed diagnosis of ER+/HER2- breast cancer
- •Advanced or metastatic breast cancer
- •Must be able to swallow tablets and capsules
排除标准
- •Symptomatic CNS metastases
- •Patients whose laboratory values do not meet protocol criteria
- •Clinically significant cardiac disease
- •Impaired gastrointestinal function (GI) or GI disease that may significantly alter the absorption of oral medications
- •Other protocol defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Arm A
Patients will get LSZ102 single agent during dose escalation.
干预措施: LSZ102 (Drug)
Arm B
Patients will get LSZ102 in combination with LEE011 during dose escalation.
干预措施: LSZ102 (Drug)
Arm B
Patients will get LSZ102 in combination with LEE011 during dose escalation.
干预措施: LEE011 (Drug)
Arm C
Patients will get LSZ102 in combination with BYL719 during dose escalation.
干预措施: LSZ102 (Drug)
Arm C
Patients will get LSZ102 in combination with BYL719 during dose escalation.
干预措施: BYL719 (Drug)
Arm 1
Patients will get LSZ102 single agent during dose expansion
干预措施: LSZ102 (Drug)
Arm 2
Patients will get LSZ102 + LEE011 (LEE011 intermittent regimen) during dose expansion
干预措施: LSZ102 (Drug)
Arm 2
Patients will get LSZ102 + LEE011 (LEE011 intermittent regimen) during dose expansion
干预措施: LEE011 (Drug)
Arm 3
Patients will get LSZ102 + LEE011 (LEE011 continuous regimen) during dose expansion
干预措施: LSZ102 (Drug)
Arm 3
Patients will get LSZ102 + LEE011 (LEE011 continuous regimen) during dose expansion
干预措施: LEE011 (Drug)
Arm 4
Patient will get LSZ102 in combination with BYL719 during dose expansion
干预措施: LSZ102 (Drug)
Arm 4
Patient will get LSZ102 in combination with BYL719 during dose expansion
干预措施: BYL719 (Drug)
结局指标
主要结局
Safety and tolerability of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719
时间窗: Approximately 3 years
Incidence and severity of adverse events, serious adverse events, clinical laboratory values, vital signs, ECGs, dose interruptions, dose reductions and dose intensity.
Incidence of dose limiting toxicities (DLTs)
时间窗: Day 1 - Day 28 of Cycle 1 (28 day cycle)
The dose escalation part of the study will be guided by well-established statistical methods/models to estimate the maximum tolerated doses (MTD)and/or recommended doses for expansion (RDE). Safety, pharmacokinetic and pharmacodynamics data will guide dose escalation decisions.
次要结局
- Disease control rate (DCR)(3 years)
- Plasma concentration under fasted condition and fed condition(Up to 2 cycles (28 day cycle))
- Duration of Response (DOR)(3 years)
- Progression Free Survival (PFS)(3 years)
- Plasma concentration of study medications(1 cycle (28 day cycle))
- PK parameter Cmin(6 cycles (28 day cycle))
- Overall response rate (ORR)(Approximately 3 years)
- Levels of Pharmacodynamic marker Estrogen receptor (ER)(3 years)
- Levels of Pharmacodynamic marker pS6(3 years)
- Levels of Pharmacodynamic marker Progesterone receptor (PgR)(3 years)
- Pharmacokinetics (PK) parameter AUC(6 cycles (28 day cycle))
- PK parameter Cmax(6 cycles (28 day cycle))
- PK parameter Tmax(6 cycles (28 day cycle))