A PHASE I STUDY OF ERY974 IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC HEPATOCELLULAR CARCINOMA
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 179
- 试验地点
- 11
- 主要终点
- Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Electrocardiograms in triplicate) [Dose escalation part]
研究概览
简要总结
This is a multicenter, open-label, dose-escalation study designed to determine the maximum tolerated dose (MTD) by evaluating dose-limiting toxicities (DLTs) and to evaluate the safety, tolerability, pharmacokinetics, anti-tumor effect, and biomarkers of ERY974 in combination with atezolizumab and bevacizumab following premedication with tocilizumab in patients with locally advanced or metastatic HCC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Aged ≥18 years at time of informed consent
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
- •HCC that has been histologically confirmed
排除标准
- •Previous or concomitant autoimmune disease
- •Uncontrolled diabetes mellitus and hypertension
- •Concurrent New York Heart Association (NYHA) Class ≥II congestive heart failure, myocardial infarction, arrhythmia, or unstable angina, or a history thereof within 6 months before enrollment.
- •Concurrent symptomatic cerebrovascular disorder (e.g., subarachnoid hemorrhage, cerebral infarction, or transient ischemic attack), or a history thereof within 6 months before enrollment.
- •Symptomatic, untreated, or actively progressing CNS metastases
研究组 & 干预措施
Dose escalation part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent and to determine the MTD by evaluating DLTs of in patients with locally advanced or metastatic HCC.
干预措施: ERY974 (Drug)
Dose escalation part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent and to determine the MTD by evaluating DLTs of in patients with locally advanced or metastatic HCC.
干预措施: Tocilicumab (Drug)
Dose escalation part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent and to determine the MTD by evaluating DLTs of in patients with locally advanced or metastatic HCC.
干预措施: Atezolizumab (Drug)
Dose escalation part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent and to determine the MTD by evaluating DLTs of in patients with locally advanced or metastatic HCC.
干预措施: Bevacizumab (Drug)
Expansion part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent To evaluate the anti-tumor effect.
干预措施: ERY974 (Drug)
Expansion part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent To evaluate the anti-tumor effect.
干预措施: Tocilicumab (Drug)
Expansion part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent To evaluate the anti-tumor effect.
干预措施: Atezolizumab (Drug)
Expansion part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent To evaluate the anti-tumor effect.
干预措施: Bevacizumab (Drug)
Concomitant use part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab and to determine the MTD.
干预措施: ERY974 (Drug)
Concomitant use part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab and to determine the MTD.
干预措施: Tocilicumab (Drug)
Concomitant use part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab and to determine the MTD.
干预措施: Atezolizumab (Drug)
Concomitant use part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab and to determine the MTD.
干预措施: Bevacizumab (Drug)
Biomarker part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent and to evaluate the biomarkers.
干预措施: ERY974 (Drug)
Biomarker part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent and to evaluate the biomarkers.
干预措施: Tocilicumab (Drug)
Biomarker part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent and to evaluate the biomarkers.
干预措施: Atezolizumab (Drug)
Biomarker part
Patients will receive ERY974 in combination with atezolizumab and bevacizumab after administering ERY974 as a single agent and to evaluate the biomarkers.
干预措施: Bevacizumab (Drug)
Mono dose escalation part
Patients will receive ERY974 as a single agent and to determine the MTD by evaluating DLTs of in patients with locally advanced or metastatic HCC.
干预措施: ERY974 (Drug)
Mono dose escalation part
Patients will receive ERY974 as a single agent and to determine the MTD by evaluating DLTs of in patients with locally advanced or metastatic HCC.
干预措施: Tocilicumab (Drug)
Mono dose escalation part
Patients will receive ERY974 as a single agent and to determine the MTD by evaluating DLTs of in patients with locally advanced or metastatic HCC.
干预措施: Atezolizumab (Drug)
Mono dose escalation part
Patients will receive ERY974 as a single agent and to determine the MTD by evaluating DLTs of in patients with locally advanced or metastatic HCC.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Electrocardiograms in triplicate) [Dose escalation part]
时间窗: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Heart Rate
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part]
时间窗: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0
Anti-tumor activity of ERY974 [Mono dose escalation part]
时间窗: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Objective Response Rate (ORR) is defined as proportion of patients who had a confirmed complete response (CR) or partial response (PR), as determined by the investigator with use of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Dose limiting toxicities) [Dose escalation part]
时间窗: At the end of Cycle 2 (Cycle 1 is 14day, Cycle 2 or later is 21days)
Incidence and nature of DLTs
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part]
时间窗: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Area under the concentration versus time curve (AUC) of ERY974
Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab from initiation (Dose limiting toxicities) [Concomitant use part]
时间窗: At the end of Cycle 1 (each Cycle is 21days)
Incidence and nature of DLTs
Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab [Expansion part]
时间窗: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Objective Response Rate (ORR) is defined as proportion of patients who had a confirmed complete response (CR) or partial response (PR), as determined by the investigator with use of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part]
时间窗: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Area under the concentration versus time curve (AUC) of ERY974
Biomarkers of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part]
时间窗: From screening to 6weeks
Gene expression
Safety of ERY974 (Dose limiting toxicities) [Mono dose escalation part]
时间窗: From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.
Heart Rate
次要结局
- Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Expansion part](From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.)
- Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab from initiation [Concomitant use part](From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to about 52 weeks.)
- Safety of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part](From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.)
- Anti-tumor activity of ERY974 in combination with atezolizumab and bevacizumab [Dose escalation part](From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to about 52 weeks.)
- Safety and tolerability of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part](From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.)
- Safety, tolerability and pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Expansion part](From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.)
- Safety, tolerability and pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab (Adverse Events) [Biomarker part](From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.)
- From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.(From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.)
- Pharmacokinetics of ERY974 [Mono dose escalation part](From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.)
- Biomarkers of ERY974 [Mono dose escalation part](From screening to 6weeks)
- Pharmacokinetics of ERY974 in combination with atezolizumab and bevacizumab [Biomarker part](From first dose until 28 days after the last dose of study treatment, assessed up to about 52 weeks.)