A Phase 1/2 Open-Label Study of the Safety, Tolerability and Efficacy of the Selective Inhibitor of Nuclear Export (SINE) Compound Eltanexor (KPT-8602) in Patients with Newly Diagnosed and Relapsed/Refractory Cancer Indications
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 277
- 试验地点
- 46
- 主要终点
- Part A1, A2, B, C, D, E, F: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
研究概览
简要总结
This is a first-in-human, multi-center, open-label clinical study with separate dose escalation (Phase 1) and expansion (Phase 2) stages to assess preliminary safety, tolerability, and efficacy of the second generation oral XPO1 inhibitor KPT-8602 in participants with relapsed/refractory multiple myeloma (MM), metastatic colorectal cancer (mCRC), metastatic castration resistant prostate cancer (mCRPC), higher risk myelodysplastic syndrome (HRMDS), acute myeloid leukemia (AML) and newly diagnosed intermediate/high-risk MDS.
Dose escalation and dose expansion may be included for all parts of the study as determined by ongoing study results.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Part A1: RRMM- KPT-8602 single agent; QoDx5/week
Participants received KPT-8602 once daily for 5 days per week (QDx5/week) at escalated doses (completed).
干预措施: KPT-8602 (Drug)
Part A2: RRMM- KPT-8602 single agent; QoDx3/week
Participants received KPT-8602 once daily for 3 days per week (QoDx3/week). The starting dose for Part A2 will be informed by Part A1 (completed).
干预措施: KPT-8602 (Drug)
Part B: RRMM- KPT-8602 with low-dose dexamethasone; QDx5/week
Participants received KPT-8602 for 5 consecutive days (QDx5/week) in combination with low dose dexamethasone (20 milligram [mg] on Days 1, 3, 8, 10, 15, 17, 22, and 24 of each 28-day cycle) (completed).
干预措施: KPT-8602 (Drug)
Part B: RRMM- KPT-8602 with low-dose dexamethasone; QDx5/week
Participants received KPT-8602 for 5 consecutive days (QDx5/week) in combination with low dose dexamethasone (20 milligram [mg] on Days 1, 3, 8, 10, 15, 17, 22, and 24 of each 28-day cycle) (completed).
干预措施: Dexamethasone (Drug)
Part C: CRC- KPT-8602 single agent
Participants were treated with KPT-8602 at a dose and schedule that has been cleared in Part A (completed).
干预措施: KPT-8602 (Drug)
Part D: mCRPC- KPT-8602 single agent
Participants were treated with KPT-8602 at a dose and schedule that has been cleared in Part A (completed).
干预措施: KPT-8602 (Drug)
Part H: AML Maintenance Therapy- KPT-8602 single agent
Participants with high-risk acute myeloid leukemia (AML) prior to transplant will be enrolled to receive maintenance therapy with KPT-8602 post-allogeneic stem cell transplantation. The dose for KPT-8602 will be 10 mg (RP2D from Part F) oral, to be administered once daily from Day 1 to Day 21 (Weeks 1 to 3) on a 28-day cycle.
干预措施: KPT-8602 (Drug)
Part E: mCRPC- KPT-8602 with abiraterone and corticosteroids
Participants were treated with KPT-8602 at a dose and schedule that had been cleared in Part A in combination with abiraterone and corticosteroids. Participants continued to receive the dose and schedule of abiraterone and corticosteroids that they were receiving at the time of enrollment (completed).
干预措施: KPT-8602 (Drug)
Part F: High-risk Myelodysplastic Syndrome (MDS)- KPT-8602 single agent
Participants were treated with KPT-8602 at a dose and schedule that had been cleared in Part A. In select cases (for example, participants achieving stable disease [SD], hematological improvement [HI], partial response [PR] and tolerating treatment, etc.), the dose may be escalated 1 level based on safety and efficacy considerations (completed).
干预措施: KPT-8602 (Drug)
Part F Phase 2: RR High-risk MDS- KPT-8602 single agent
Participants will be enrolled at recommended Phase 2 doses (RP2D) of 10 mg daily on Days 1 to 5 of each week, in a dose expansion, based upon the results from the Phase 1 portion of Part F.
干预措施: KPT-8602 (Drug)
Part G: Newly Diagnosed Intermediate/High-Risk MDS -KPT-8602 with ASTX727
Participants will receive KPT-8602 once daily at escalated doses. The starting dose for KPT-8602 is 5 mg orally once daily from Day 8 to Day 28 (Weeks 2 to 4) on a 28-day cycle in combination with ASTX727.
干预措施: KPT-8602 (Drug)
Part G: Newly Diagnosed Intermediate/High-Risk MDS -KPT-8602 with ASTX727
Participants will receive KPT-8602 once daily at escalated doses. The starting dose for KPT-8602 is 5 mg orally once daily from Day 8 to Day 28 (Weeks 2 to 4) on a 28-day cycle in combination with ASTX727.
干预措施: ASTX727 (Drug)
结局指标
主要结局
Part A1, A2, B, C, D, E, F: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
时间窗: Approximately 4 weeks
Part A1, A2, B, C, D, E, F: Overall Response Rate (ORR)
时间窗: Approximately 8 years
Part A1, A2, B, C, D, E, F: Clinical Benefit Rate (CBR)
时间窗: Approximately 8 years
Part A1, A2, B, C, D, E, F: Duration of Response (DOR)
时间窗: Approximately 8 years
Part A1, A2, B, C, D, E, F: Progression-free Survival (PFS)
时间窗: Approximately 8 years
Part A1, A2, B, C, D, E, F: Overall Survival (OS)
时间窗: Approximately 8 years
Part A1, A2, B, C, D, E, F: Duration of Clinical Benefit Rate (CBR)
时间窗: Approximately 8 years
Part A1, A2, B, C, D, E, F: Disease Control Rate (DCR)
时间窗: Approximately 8 years
Part A1, A2, B, C, D, E, F: Duration of DCR
时间窗: Approximately 8 years
Part F Phase 2: ORR
时间窗: Approximately 8 years
Part G: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
时间窗: Approximately 8 years
Part H: 2- Year Progression-free Survival (PFS)
时间窗: Approximately Up to 2 years
次要结局
- Part A1, A2, B, C, D, E, F, H: Area Under the Plasma Concentration Time Curve from Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Eltanexor(Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years)
- Part A1, A2, B, C, D, E, F, H: Maximum Observed Plasma Concentration (Cmax) of Eltanexor(Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years)
- Part A1, A2, B, C, D, E, F, H: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Eltanexor(Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years)
- Part A1, A2, B, C, D, E, F, H: Apparent Terminal Half Life (t1/2) of Eltanexor(Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years)
- Part A1, A2, B, C, D, E, F, H: Apparent Total Body Clearance Eltanexor(Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years)
- Part A1, A2, B, C, D, E, F, H: Apparent Volume of Distribution During Terminal Phase (VZ/f) of Eltanexor(Pre-dose 2 hours post-dose Cycle 1 Day 1 and 15; Pre-dose 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 21 and 26; 24 hours post-dose Cycle 1 Day 2, 22, and 27; 48 hours post-dose Cycle 1 Day 23 and 28 and up to approximately 8 years)
- Part F Phase 2: Overall Survival (OS)(Approximately 8 years)
- Part F Phase 2: 6-Month Overall Survival (OS)(Approximately Up to 6 Months)
- Part F Phase 2: Progression-free Survival (PFS)(Approximately 8 years)
- Part F Phase 2: Disease Control Rate (DCR)(Approximately 8 years)
- Part F Phase 2: Duration of Response (DOR)(Approximately 8 years)
- Part F Phase 2: Rate of Conversion from Red Blood Cell (RBC) Transfusion Dependence to Independence(Approximately 8 years)
- Part F Phase 2: Rate of Conversion from Platelet Transfusion Dependence to Independence(Approximately 8 years)
- Part G: Overall Response Rate (ORR)(Approximately 8 years)
- Part G: Duration of Response (DOR)(Approximately 8 years)
- Part H: Rate of Minimal Residual Disease (MRD) Conversion from Positive to Negative(Approximately 8 years)
- Part H: Time to Minimal Residual Disease (MRD) Negativity(Approximately 8 years)
- Part H: Percentage of Participants with Acute and Chronic Graft-versus-Host Disease (GVHD)(Approximately 8 years)
- Part H: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Approximately 8 years)
- Part H: Overall Survival (OS)(Approximately 8 years)