An Open Label, Multi-center, Phase I Clinical Study to Evaluate the Safety, Effectiveness and Pharmacokinetic Characteristics of SIM1803-1A in Patients With Locally Advanced/Metastatic Solid Tumors With NTRK, ROS1 or ALK Gene Fusion Mutations.
试验速览
- 阶段
- 1 期
- 入组人数
- 243
- 试验地点
- 1
- 主要终点
- Area under the concentration-time curve of SIM1803-1A in plasma from time 0 to 24 hours in fasted state (AUC(0-24)_fasted)
研究概览
简要总结
This research study is done to test the safety, effectiveness and pharmacokinetic characteristics of SIM1803-1A in patients with locally advanced/metastatic solid tumors with NTRK, ROS1 or ALK gene fusion mutations. The cancer must have a change in a particular gene (NTRK1, NTRK2, NTRK3, ROS1 or ALK). SIM1803-1A is a drug that blocks the actions of these NTRK/ ROS1 /ALK genes in cancer cells and can therefore be used to treat cancer.
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
- •Adult patients with a locally advanced or metastatic solid tumor that has progressed or was nonresponsive to available therapies, are unfit for standard chemotherapy or for which no standard or available curative therapy exists；Proof of a malignancy harboring a NTRK、ROS1 or ALK fusion；Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 and a life expectancy of at least 3 month；Adequate hematologic, hepatic, and renal function；Signed informed consent form；
排除标准
- •Any contraindications as listed in the local approved product information；Patients with unstable primary central-nervous-system tumors or metastasis, exceptions possible；Pregnancy or lactation；Clinically significant active cardiovascular disease or history of myocardial infarction；Participation in an investigational program with interventions outside of routine clinical practice；Prior treatment with other kinase inhibitor with tropomyosin receptor kinase inhibition；Active uncontrolled systemic bacterial, viral, or fungal infection；Current treatment with a strong CYP3A4 inhibitor or inducer；
研究组 & 干预措施
adult patients_Dose 6
干预措施: SIM1803-1A (Drug)
adult patients_Dose 7
干预措施: SIM1803-1A (Drug)
adult patients_Dose 8
干预措施: SIM1803-1A (Drug)
adult patients_Dose 1
干预措施: SIM1803-1A (Drug)
adult patients_Dose 2
干预措施: SIM1803-1A (Drug)
adult patients_Dose 3
干预措施: SIM1803-1A (Drug)
adult patients_Dose 4
干预措施: SIM1803-1A (Drug)
adult patients_Dose 5
干预措施: SIM1803-1A (Drug)
结局指标
主要结局
Area under the concentration-time curve of SIM1803-1A in plasma from time 0 to 24 hours in fasted state (AUC(0-24)_fasted)
时间窗: Up to 1 day
Area under the concentration-time curve of SIM1803-1A in plasma from time 0 to 24 hours in fasted state (AUC(0-24)_fasted)
Area under the concentration-time curve of SIM1803-1A in plasma from time 0 to infinity in fasted state (AUC_fasted)
时间窗: Up to 3 days
Area under the concentration-time curve of SIM1803-1A in plasma from time 0 to infinity in fasted state (AUC_fasted)
Number of participants with treatment-emergent adverse events (TEAEs)
时间窗: Up to 24 weeks
Number of participants with treatment-emergent adverse events (TEAEs)
Time to maximum concentration of SIM1803-1A in plasma (Tmax)
时间窗: Predose and 0.25, 0.5, 1, 2, 4, 8，12，24and 48 hours after drug administration on Days 1 and 8 of Cycle 1（each cycle is 21 days)
Time to maximum concentration of SIM1803-1A in plasma (Tmax)
Number of participants with adverse events
时间窗: 5 years
Number of participants with adverse events
Severity of adverse events
时间窗: 5 years
Severity of adverse events
Maximum tolerated dose
时间窗: 5 years
Maximum tolerated dose
Recommended dose for dose expansion
时间窗: 5 years
Recommended dose for dose expansion
Maximum concentration of SIM1803-1A in plasma (Cmax)
时间窗: Predose and 0.25, 0.5, 1, 2, 4, 8，12，24and 48 hours after drug administration on Days 1 and 8 of Cycle 1（each cycle is 21 days）
Maximum concentration of SIM1803-1A in plasma (Cmax)
次要结局
- Overall Response Rate (ORR)(Up to 60 months)
- Duration of Response (DOR)(Up to 60 months)
- progression-free survival（PFS）(Up to 60 months)