NCT04194801已完成1 期
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)
适应症
干预措施
相关药物
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
- •Voluntarily participate in the clinical study. Fully understand and get informed of this study and sign the Informed Consent Form (ICF).
- •≥18 years of age on day of signing the informed consent.
- •Unresectable locally advanced or metastatic hepatocellular carcinoma as confirmed by histology or cytology.
- •Stage B or C based on Barcelona Clinic Liver Cancer (BCLC) staging system; In case of Stage B, subject must be ineligible for surgery and/or local therapy, or has progressed after surgery and/or local therapy or refuses surgery and/or local treatment.
- •For Phase Ib, subject has failed after or is unsuitable for the standard systemic therapy against HCC. For Phase II, subject has not previously received systemic therapy.
- •At least one measurable lesion as evaluable by RECIST version 1.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1 point.
- •A-level Child-Pugh score.
- •Expected survival≥3 months.
- •For Phase Ib and II, fresh or archived tumor tissue should be provided for analysis in the central laboratory.
- •The function of the main organs was basically normal and met the requirements of the protocol.
- •For subject with HCV infection, HCV antiviral treatment with the locally approved and available HCV antiviral therapy can be received.
- •For subjects with HBV infection, HBV DNA ≤ 2,000 IU/ml at Screening.
- •For female subjects of childbearing potential, serum pregnancy test must be negative within 7 days prior to randomization. Except for female subjects who have been recorded as surgically sterilized or who are postmenopausal, female subjects of childbearing potential or male subjects and their partners must agree to use effective contraception from the signature of the informed consent form (ICF) until at least 6 months after the last dose of study drug.
排除标准
- •tumor thrombus in the main portal vein (VP4) by imaging, involving the inferior vena cava or the heart.
- •Prior history of hepatic encephalopathy.
- •History of liver surgery and/or local treatment for HCC (intervention, ablation therapy, absolute alcohol injection, etc.) or radiotherapy, etc. within 4 weeks prior to first dose.
- •Active or documented gastrointestinal bleeding within 6 months (e.g. esophageal or gastric varices, ulcer bleeding).
- •Presence of ascites detected by physical examination or clinical symptoms caused by ascites during the screening period, or ascites that need for special treatment, such as repeated drainage, intraperitoneal drug infusion, etc.
- •Presence of meningeal metastasis or central nervous system (CNS) metastatic lesions.
- •Subject has clinically significant, uncontrolled cardiovascular disease.
- •History of definite interstitial lung disease or non-infectious pneumonia except that caused by local radiotherapy; history of active tuberculosis.
- •Any serious acute, chronic infections that require systemic antimicrobial, antifungal or antiviral therapy at screening, excluding viral hepatitis.
- •Malabsorption syndrome or inability to take the study drug orally for other reasons.
- •Had primary malignancies other than HCC within 5 years.
- •Subject has had major surgery within 4 weeks prior to first dose (procedures such as central venous cannulation, biopsy, and feeding tube placement are not considered as major surgery).
- •Previously received FGFR4 inhibitor treatment.
- •Blood transfusion, use of hematopoietic stimulating factors [including G-CSF (granulocyte colony stimulating factor), GM-CSF (granulocyte-macrophage colony stimulating factor), EPO (erythropoietin) and TPO (thrombopoietin)] and human albumin preparations within 14 days prior to first dose.
- •Requiring corticosteroids (dose equivalent to > 10 mg/day of Prednisone) or other immunosuppressive drugs within 14 days prior to first dose for systemic therapy.
- •Use of traditional Chinese medicine with anti-liver cancer indication within 14 days prior to the first dose.
- •Subject has received potent CYP3A4 inhibitors and/or inducers within 2 weeks prior to first dose.
- •Concurrent HBV and HCV infection.
- •Subjects with known human immunodeficiency virus (HIV) infection.
- •Lactating women.
- •Subjects with a history of hypersensitivity or hypersensitivity to any of the components of the investigational drug.
- •Circumstances that in the opinion of the investigator would preclude participation in the study.
- •Subjects who are unwilling or unable to follow the study procedures as defined.
- •With the exception of alopecia, all toxicities from prior anticancer therapies and other therapies did not recover to ≤ Grade 1 (per CTCAE v5.0) prior to the first dose of study drug.
- •Subjects who have received prior allogeneic stem cell or solid organ transplantation.
研究组 & 干预措施
Phase Ib: Fisogatinib (BLU-554) 400mg in combination with Sugemalimab (CS1001) 1200mg
Experimental
干预措施: Phase Ib: Fisogatinib (BLU-554) 400mg in combination with Sugemalimab (CS1001) 1200mg (Drug)
Phase Ib: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg
Experimental
干预措施: Phase Ib: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg (Drug)
Phase II: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg
Experimental
干预措施: Phase II: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg (Drug)
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 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.)
- 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.)
- 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).)
研究者
研究点 (3)
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