A Multicenter, Open-label, Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-653 in Treatment of Patients With Advanced Malignant Solid Tumors and Tenosynovial Giant Cell Tumor
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 113
- 试验地点
- 5
- 主要终点
- Occurrence of Dose-Limiting Toxicities(DLTs)
研究概览
简要总结
To evaluate the safety and tolerability of HMPL-653 in patients with advanced solid tumors who have failure of standard of care or can not tolerate standard of care or those with TGCT, and to determine the maximum tolerated dose (MTD) and/or the recommended phase II clinical study dose (RP2D) of HMPL-653 in patients with advanced solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to understand and willing to sign the ICF.
- •Aged 18 to 75 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy at least 12 weeks.
- •Adequate bone marrow, liver and kidney function.
排除标准
- •Toxicity associated with previous antitumor therapy not recovered to ≤CTCAE grade 1；
- •Previous treatment with anti-CSF1R therapy and have progressive disease;
- •Receiving approved systematic antitumor therapy or in the treatment period of other interventional clinical study within 4 weeks prior to the first dose.
- •Patients with central nervous system (CNS) malignant tumor or malignant solid tumor with known CNS metastasis;
- •Pregnant or lactating women.
研究组 & 干预措施
HMPL-653 open-label treatment arm
Dose-escalation Stage:
Participants will be treated with escalating doses of HMPL-653 to determine the MTD and RP2D.
Dose-expansion Stage:
Participants will be enrolled in the expansion stage to better characterize the safety, tolerability, PK variability, and preliminary efficacy of HMPL-653 in TGCT and specific advanced solid tumors.
干预措施: HMPL-653 (Drug)
结局指标
主要结局
Occurrence of Dose-Limiting Toxicities(DLTs)
时间窗: up to 33 days
To evaluate the safety and tolerability of HMPL-653 for dose escalation period
Maximum tolerated dose (MTD)
时间窗: up to 12 months
The Maximum tolerated dose of HMPL-653
Recommended phase II dose (RP2D)
时间窗: up to 12 months
Recommended phase II dose of HMPL-653
次要结局
- Pharmacokinetic-AR(up to 9 weeks)
- Pharmacokinetic-Cmax(up to 9 weeks)
- Pharmacokinetic-Tmax(up to 9 weeks)
- Pharmacokinetic-Ctrough(up to 9 weeks)
- Pharmacokinetic-t1/2(up to 9 weeks)
- Pharmacokinetic-AUC0-t(up to 9 weeks)
- Pharmacokinetic-AUC0-∞(From first dose up to C3D1, estimated up to 9 weeks)
- Pharmacokinetic-AUC0-τ(up to 9 weeks)
- Pharmacokinetic-CL/F(up to 9 weeks)
- Pharmacokinetic-Vz/F(up to 9 weeks)
- Objective response rate (ORR)(12 months)
- Progression-free survival (PFS)(12 months)
- Disease control rate (DCR)(12 months)
- Time to response (TTR)(12 months)
- Duration of response (DoR)(12 months)
- Overall survival (OS)(24 months)