A Muti-center, Open-label, Multiple-dose Phase Ib/II Study to Assess the Safety, Tolerability, Pharmacokinetics, Anti-tumor Efficacy of Fisogatinib(BLU-554) in Combination With CS1001 in Subjects With Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 3
- 主要终点
- Phase Ib: Safety and Tolerance
研究概览
简要总结
This study will evaluate the safety, tolerability, pharmacokinetic and efficacy of fisogatinib (formerly known as BLU-554) in combination with CS1001 in patients with locally advanced or metastatic hepatocellular carcinoma (HCC)
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
结局指标
主要结局
Phase Ib: Safety and Tolerance
时间窗: Safety and tolerance assessments continued for the duration of treatment. AEs and SAEs will be collected from time of signature of main informed consent, throughout the treatment period and including the follow-up period, up to approximate 22 months.
An AE was any untoward medical occurrence after clinical study subjects receive study drug. An SAE was any event that meets any the following criteria: death, life-threatening; inpatient hospitalization or prolongation, persistent or significant disability/incapacity;congenital malformation/birth defects and significant medical events. AE and SAE were graded by CTCAE version 5.0 by severity, from Grade 1 mild to Grade 5 death related AE.
Phase Ib: Patients With Event(s) of Dose-limiting Toxicity
时间窗: Cycle 1 (21 days) of treatment
Number of DLT (Dose-limiting toxicity) During the Administration of BLU-554 in Combination with CS1001. All toxicity or adverse events (AEs) are graded according to NCI-CTCAE 5.0. Any AE occurring during C1 (21 days) that is not clearly caused by something other than investigational drug.
Phase II: Objective Response Rate (ORR) Assessed by Investigator Based on RECIST Version 1.1
时间窗: Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.
Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1 .1) for target lesions and assessed by MRI/ CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \> =30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. Percentage of subjects who achieve objective tumor response (CR or PR) will be summarized.
次要结局
- Patients With Anti-CS1001 Antibody(Pre-dose of Cycle 1, 2, 4, 5, 7, 10, 13, 16 and every 8 cycles thereafter. Up to 22 months.)
- Overall Survival(Subject should be followed from time of registration till the time of subject death. Up to 22 months.)
- Disease Control Rate by PD-L1 Protein Level(Imaging (CT or MRI) assessments by FGF19 protein and PD-L1 protein level will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.)
- Disease Control Rate Assessed by Investigator(Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.)
- Duration of Response Assessed by Investigator(Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.)
- Phase Ib: Objective Response Rate (ORR) Assessed by Investigator Based on RECIST Version 1.1(Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.)
- Objective Response Rate (ORR) by PD-L1 Protein Level(Imaging (CT or MRI) assessments by FGF19 protein and PD-L1 protein level will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.)
- Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of Fisogatinib (BLU-554)(For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).)
- Pharmacokinetic Parameters of Time to Maximum Serum Concentration (Tmax) of Fisogatinib (BLU-554)(For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).)
- Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of Sugemalimab (CS1001)(For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).)
- Pharmacokinetic Parameters of Time to Maximum Serum Concentration (Tmax) of Sugemalimab (CS1001)(For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).)
- Phase II: Safety and Tolerance(Safety and tolerance assessments continued for the duration of treatment. AEs and SAEs will be collected from time of signature of main informed consent, throughout the treatment period and including the follow-up period, up to approximate 22 months.)
- Pharmacokinetic Parameters of Clearance at Steady State (CLss) of Fisogatinib (BLU-554)(For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).)
- Pharmacokinetic Parameters of Accumulation Ratio of Fisogatinib (BLU-554)(For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).)
- Pharmacokinetic Parameters of Area Under the Serum Concentration-time Curve (AUC) of Fisogatinib (BLU-554)(For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).)
- Pharmacokinetic Parameters of Clearance at Steady State (CLss) of Sugemalimab (CS1001)(For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).)
- Progression-free Survival Assessed by Investigator(Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.)
- Time to Progression Assessed by Investigator(Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.)
- Pharmacokinetic Parameters of Area Under the Serum Concentration-time Curve (AUC ) of Sugemalimab (CS1001)(For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).)
- Pharmacokinetic Parameters of Accumulation Ratio of Sugemalimab (CS1001)(For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).)