A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BLU-554 in Patients With Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 146
- 试验地点
- 41
- 主要终点
- Maximum tolerated dose (MTD) on qd and bid schedules
研究概览
简要总结
This is a Phase 1, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antineoplastic activity of fisogatinib (formerly known as BLU- 554) administered orally in patients with FGF19 IHC+ hepatocellular carcinoma (HCC). The study consists of 3 parts, a dose-escalation part (Part 1), an expansion part (Part 2) exploring a once daily (qd) dosing schedule at the recommended Phase 2 dose (RP2D), and a Part 3 expansion of the qd dosing schedule at the RP2D in TKI naive patients.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of HCC by histological examination or by non-invasive criteria according to European Association for the Study of the Liver (EASL) or American Association for the Study of Liver Disease (AASLD) guidelines (Part 1, 2 and 3).
- •For Part 1 and 2, the patient has unresectable disease and has been previously treated with sorafenib, has declined treatment with sorafenib, or does not have access to sorafenib.
- •For Part 3, the patient has not received prior treatment with a TKI.
- •Child-Pugh class A with no clinically apparent ascites
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •For Part 1, willing to provide archived tumor tissue (if available) and willing to undergo pre- and on-treatment tumor biopsy (if considered safe and medically feasible by the treating investigator)
- •For Part 2 and 3, all patients must have an FGF19 IHC result available. Only FGF19 IHC+ HCC patients will be eligible for Part
排除标准
- •Central nervous system metastases
- •Platelet count <75,000/mL
- •Absolute neutrophil count <1000/mL
- •Hemoglobin <8 g/dL
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5x the upper limit of normal (ULN)
- •Total bilirubin >2.5 mg/dL
- •International normalized ratio (INR) >2.3 or prothrombin time (PT) >6 seconds above control
- •Estimated (Cockroft-Gault formula) or measured creatinine clearance <40 mL/min
研究组 & 干预措施
Fisogatinib (BLU-554)
Fisogatinib (BLU-554) capsules for oral administration.
干预措施: Fisogatinib (BLU-554) (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) on qd and bid schedules
时间窗: During cycle 1 (28 days) of treatment and will be determined by approximately 24 months after start of the study or earlier
Recommended Phase 2 dose of fisogatinib (BLU-554) on qd and bid schedules
时间窗: At the end of every cycle (28 days) of treatment and will be determined by approximately 24 months after start of the study or earlier
Number of patients with adverse events, serious adverse events and changes in physical findings, vital signs, clinical laboratory results and ECG findings
时间窗: Every cycle (28 days) for approximately 24 months or earlier if patient terminates from the study
次要结局
- Levels of FGF19 in blood and tumor samples(Cycle 1 (Day 28))
- Maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules(Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study))
- Fibroblast growth factor 19 (FGF19) status in tumor tissue(Cycle 2 (Day 56))
- Preliminary evidence of fisogatinib (BLU-554) antineoplastic activity(Screening, Day 1 of every odd numbered cycle starting with Cycle 3, End of treatment (at approximately 24 months or earlier if patient terminates from the study) and every three months post EOT)
- Time to maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules(Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study))