A Phase 1b/2 Study of Safety and Efficacy of MLN0128 (Dual TORC1/2 Inhibitor) in Combination With Exemestane or Fulvestrant Therapy in Postmenopausal Women With ER+/HER2- Advanced or Metastatic Breast Cancer That Has Progressed on Treatment With Everolimus in Combination With Exemestane or Fulvestrant
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 118
- 试验地点
- 40
- 主要终点
- Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This is a phase 1b/2 study of the safety and efficacy of sapanisertib (MLN0128) in combination with exemestane or fulvestrant therapy in women with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced or metastatic breast cancer who progressed on treatment with everolimus in combination with exemestane or fulvestrant.
详细描述
The drug being tested in this study is called sapanisertib (MLN0128). Sapanisertib is being tested in women with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced or metastatic breast cancer who progressed on treatment with everolimus. This study will look at the safety and efficacy of sapanisertib when given in combination with exemestane or fulvestrant.
The study enrolled 118 patients. This study has two phases: phase 1 and phase 2. Phase 1 has 2 parts. In part 1 of phase 1, unmilled active pharmaceutical ingredient (API) capsules were administered, while in part 2, capsules based on milled API were administered.
- Phase 1 (Part 1): sapanisertib 5 mg (unmilled) + exemestane
- Phase 1 (Part 1): sapanisertib 5 mg (unmilled) + fulvestrant
- Phase 1 (Part 2): sapanisertib 3 mg (milled) + exemestane
- Phase 1 (Part 2): sapanisertib 3 mg (milled) + fulvestrant
- Phase 1 (Part 2): sapanisertib 4 mg (milled) + exemestane
In phase 2, participants were enrolled into one of 2 parallel cohorts, depending on the quality and/or duration of their prior response to everolimus in combination with either exemestane (any country) or fulvestrant (US only).
Everolimus-Resistant Cohort: patients who had progressed on treatment with everolimus in combination with either exemestane (any country) or fulvestrant (US only) without achieving an objective response (CR or PR) or after achieving stable disease for <6 months as their best response.
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
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant
Sapanisertib 5 mg, unmilled API capsule, once daily in a 28-day cycle plus fulvestrant 500 mg, injection, intramuscularly (IM), once on Day 1 of each cycle (Up to 57 cycles).
干预措施: Sapanisertib (Drug)
Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane
Sapanisertib 5 mg, unmilled active pharmaceutical ingredient (API) capsule, once daily in a 28-day cycle plus exemestane 25 mg, tablets, once daily in a 28-day cycle (Up to 12 cycles).
干预措施: Exemestane (Drug)
Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane
Sapanisertib 5 mg, unmilled active pharmaceutical ingredient (API) capsule, once daily in a 28-day cycle plus exemestane 25 mg, tablets, once daily in a 28-day cycle (Up to 12 cycles).
干预措施: Sapanisertib (Drug)
Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant
Sapanisertib 5 mg, unmilled API capsule, once daily in a 28-day cycle plus fulvestrant 500 mg, injection, intramuscularly (IM), once on Day 1 of each cycle (Up to 57 cycles).
干预措施: Fulvestrant (Drug)
Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane
Sapanisertib 3 mg, milled API capsule, once daily in a 28-day cycle plus exemestane 25 mg, tablets, once daily in a 28-day cycle (Up to 8 cycles).
干预措施: Sapanisertib (Drug)
Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane
Sapanisertib 3 mg, milled API capsule, once daily in a 28-day cycle plus exemestane 25 mg, tablets, once daily in a 28-day cycle (Up to 8 cycles).
干预措施: Exemestane (Drug)
Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant
Sapanisertib 3 mg, milled API capsule, once daily in a 28-day cycle up to 14 cycles plus fulvestrant 500 mg, injection, IM, once on Day 1 of each cycle (Up to 14 cycles).
干预措施: Sapanisertib (Drug)
Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant
Sapanisertib 3 mg, milled API capsule, once daily in a 28-day cycle up to 14 cycles plus fulvestrant 500 mg, injection, IM, once on Day 1 of each cycle (Up to 14 cycles).
干预措施: Fulvestrant (Drug)
Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane
Sapanisertib 4 mg, milled API capsule, once daily, in a 28-day cycle plus exemestane 25 mg, tablets, once daily in a 28-day cycle (Up to 18 cycles).
干预措施: Sapanisertib (Drug)
Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane
Sapanisertib 4 mg, milled API capsule, once daily, in a 28-day cycle plus exemestane 25 mg, tablets, once daily in a 28-day cycle (Up to 18 cycles).
干预措施: Exemestane (Drug)
Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)
Sapanisertib 4 mg, milled API capsule once daily in a 28-day cycle plus exemestane 25 mg, tablets, once daily in a 28-day cycle (Up to 14 cycles) in everolimus sensitive participants.
干预措施: Sapanisertib (Drug)
Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)
Sapanisertib 4 mg, milled API capsule once daily in a 28-day cycle plus exemestane 25 mg, tablets, once daily in a 28-day cycle (Up to 14 cycles) in everolimus sensitive participants.
干预措施: Exemestane (Drug)
Phase 2:Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)
Sapanisertib 4 mg, milled API capsule once daily in a 28-day cycle plus fulvestrant 500 mg, injection IM, once on Day 1 of each cycle (Up to 17 cycles) in everolimus sensitive participants.
干预措施: Sapanisertib (Drug)
Phase 2:Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)
Sapanisertib 4 mg, milled API capsule once daily in a 28-day cycle plus fulvestrant 500 mg, injection IM, once on Day 1 of each cycle (Up to 17 cycles) in everolimus sensitive participants.
干预措施: Fulvestrant (Drug)
Phase 2: Sapanisertib 4 mg+Exemestane (Everolimus Resistant)
Sapanisertib 4 mg, milled API capsule, once daily, in a 28-day cycle plus once daily in a 28-day cycle (Up to 12 cycles) in everolimus resistant participants.
干预措施: Sapanisertib (Drug)
Phase 2: Sapanisertib 4 mg+Exemestane (Everolimus Resistant)
Sapanisertib 4 mg, milled API capsule, once daily, in a 28-day cycle plus once daily in a 28-day cycle (Up to 12 cycles) in everolimus resistant participants.
干预措施: Exemestane (Drug)
Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)
Sapanisertib 4 mg, milled API capsule, once daily in a 28-day cycle plus fulvestrant 500 mg, injection IM, once on Day 1 of each cycle (Up to 9 cycles) in everolimus resistant participants.
干预措施: Sapanisertib (Drug)
Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)
Sapanisertib 4 mg, milled API capsule, once daily in a 28-day cycle plus fulvestrant 500 mg, injection IM, once on Day 1 of each cycle (Up to 9 cycles) in everolimus resistant participants.
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: First dose of study drug through 30 days after the last dose (Up to 52 months)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug. A SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug will be determined by the Investigator.
Phase 2: Clinical Benefit Rate at 16 Weeks (CBR-16)
时间窗: Week 16
CBR-16 was defined as the percentage of participants who achieved confirmed complete response (CR) or partial response (PR) of any duration or had confirmed stable disease (SD) as best response and the first 2 or more post baseline scans had PR/SD and the duration of SD was \>112 days. Disease response was assessed for target lesions by computed tomography (CT) or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. CR is disappearance of all target lesions. PR is \>=30% decrease in the sum of the longest diameter of target lesions. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression (PD).
次要结局
- Phase 1: AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for Sapanisertib(Cycle 1 Day 15 pre-dose and multiple timepoints (Up to 8 hours) post-dose, extrapolated to 24 hours post-dose)
- Phase 1: AUC(0-last): Area Under the Plasma Concentration-time Curve From Time 0 to Last Extrapolated Concentration Over the Dosing Interval for Sapanisertib(Cycle 1 Day 15 pre-dose and multiple timepoints (Up to 8 hours) post-dose, extrapolated to last timepoint)
- Phase 2: Clinical Benefit Rate at 24 Weeks (CBR-24)(Week 24)
- Phase 2: Progression-Free Survival (PFS)(Baseline then every 2 cycles from Cycles 2 through 6, and every 3 cycles thereafter in a 28-day cycle, then every 3 months after EOT until disease progression or death (Up to 24 months))
- Phase 2: Overall Response Rate (ORR)(Baseline then every 2 cycles from Cycles 2 through 6, and every 3 cycles thereafter in a 28-day cycle up to End of Treatment (EOT) (Up to 24 months))
- Phase 2: Overall Survival (OS)(Up to 24 months)
- Phase1: Cmax: Maximum Observed Plasma Concentration for Sapanisertib(Cycle 1 Day 15 and Cycle 2 Day 1 pre-dose and multiple timepoints (Up to 8 hours) post-dose)
- Phase 2: Best Percent Change From Baseline in Tumor Size(Baseline to Month 24)
- Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Sapanisertib(Cycle 1 Day 15 and Cycle 2 Day 1 pre-dose and multiple timepoints (Up to 8 hours) post-dose)
- Phase 1: Terminal Elimination Half-life (T1/2) for Sapanisertib(Cycle 1 Day 15 pre-dose and multiple timepoints (Up to 8 hours) post-dose)