A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With Intrahepatic Cholangiocarcinoma (ICC) and Other Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 540
- 试验地点
- 46
- 主要终点
- Part 1 and Part 4: Number of patients with adverse events and serious adverse events
研究概览
简要总结
This is a Phase 1/2, open-label, FIH study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDy), and antineoplastic activity of RLY-4008, a potent and highly selective FGFR2 inhibitor, in patients with unresectable or metastatic cholangiocarcinoma (CCA) and other solid tumors. The study consists of 3 parts: a dose escalation (Part 1), a dose expansion (Part 2), and an extension (Part 3).
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Part 1: Dose Escalation
Multiple doses of RLY-4008 for oral administration.
干预措施: RLY-4008 (Drug)
Part 2: Dose Expansion
Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.
干预措施: RLY-4008 (Drug)
Part 3: Extension
Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.
干预措施: RLY-4008 (Drug)
Part 4: Rollover
Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.
干预措施: RLY-4008 (Drug)
结局指标
主要结局
Part 1 and Part 4: Number of patients with adverse events and serious adverse events
时间窗: Every cycle (4-week cycles) until study discontinuation, approximately 24 months
Part 1: Determination of maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RLY-4008
时间窗: Cycle 1 (4-week cycle) of treatment for MTD and at the end of every cycle (4-week cycles) for RP2D until study discontinuation, approximately 24 months
Part 2 and Part 3: Objective Response Rate (ORR) assessed by Independent Review Committee per RECIST v1.1
时间窗: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Part 4: Number of patients with dose interruptions
时间窗: Every 28-day cycle until end of treatment, approximately 24 months.
Part 4: Number of patients with dose reductions
时间窗: Every 28-day cycle until end of treatment, approximately 24 months.
Part 4: Number of patients with dose discontinuations
时间窗: Every 28-day cycle until end of treatment, approximately 24 months.
次要结局
- Part 2 and Part 3:Dose intensity(Every 28-day cycle until end of treatment, approximately 24 months.)
- Part 2 and Part 3: Correlation between FGFR2 genotype by central tissue assessment and antitumor response, as measured by ORR(Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months)
- Part 1: Pharmacodynamic parameters including changes in carcinoembryonic antigen (CEA)(Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months)
- Part 2 and Part 3: Number of patients with dose interruptions(Every 28-day cycle until end of treatment, approximately 24 months.)
- Part 2 and Part 3: Number of patients with dose reductions(Every 28-day cycle until end of treatment, approximately 24 months.)
- Part 1: Duration of Response (DOR) assessed by Investigator per RECIST v1.1(Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months)
- Part 1: Pharmacodynamic parameters including changes in fibroblast growth factor 23 (FGF-23)(Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months)
- Part 1: Pharmacodynamic parameters including changes in cancer antigen 19-9 (CA 19-9)(Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months)
- Part 2 and Part 3: Number of patients with dose discontinuations(Every 28-day cycle until end of treatment, approximately 24 months.)
- Part 1: FGFR2 gene status in plasma circulating tumor deoxyribonucleic acid (ctDNA) and tumor tissue(Every cycle (4-week cycles) through Cycle 3 and every other cycle thereafter until study discontinuation, approximately 24 months)
- Pharmacokinetic parameters including area under the plasma concentration versus time curve (AUC)(Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles))
- Pharmacokinetic parameters including half-life (t1/2)(Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles))
- Part 2 and Part 3: Duration of response (DOR) assessed by Investigator and Independent Review Committee per RECIST v1.1(Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months)
- Part 2 and Part 3: Progression-free survival (PFS) assessed by Investigator and Independent Review Committee per RECIST v1.1(Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months)
- Part 1: Disease Control Rate (DCR) as assessed by Investigator per RECIST v1.1(Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months)
- Part 1, Part 2, and Part 3: Objective Response Rate (ORR) as assessed by Investigator per RECIST v1.1(Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months)
- Pharmacokinetic parameters including maximum plasma drug concentration (Cmax)(Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles))
- Part 2 and Part 3: Disease control rate (DCR) assessed by Investigator and Independent Review Committee per RECIST v1.1(Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months)
- Part 2 and Part 3:Overall survival (OS)(Up to approximately 36 months.)
- Part 2 and Part 3:Change from baseline in quality of life as assessed by EORTC QLQ-C30(Approximately every 4 weeks during treatment, approximately 24 months)