A Phase Ib/II Study of Vebreltinib Plus PLB1004 in EGFR-mutated, Advanced NSCLC With MET Amplification or MET Overexpression Following EGFR-TKI
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 156
- 试验地点
- 1
- 主要终点
- Incidence of dose-limiting toxicities (DLT) as defined in the protocol.
研究概览
简要总结
Efficacy and Safety Evaluation of Vebreltinib Plus PLB1004 in EGFR TKI Relapsed MET Amplified or MET Expression in NSCLC
详细描述
Open label, multicenter Phase Ib/II clinical study to evaluate the safety, efficacy, and pharmacokinetics of Vebreltinib in combination with PLB1004 in patients with locally advanced or metastatic non-small cell lung cancer with MET overexpression or MET amplification following EGFR-TKI treatment failure.
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
- •Ability to understand and willingness to sign a written informed consent document.
- •Aged at least 18 years old.
- •Histologically or cytologically confirmed locally advanced or metastatic NSCLC (stage IIIB~IV).
- •EGFR mutations, including exon 19 deletion and exon 21 L858R.
- •C-Met overexpression and/or c-Met amplification confirmed after treatment with EGFR-TKI.
- •At least one measurable lesion as defined by RECIST V1.
- •ECOG performance status 0 to 1.
排除标准
- •Previous treatment with MET inhibitors or HGF-targeted therapy.
- •There are mutations of ALK or ROS
- •Have symptomatic and neurologically unstable central nervous system (CNS) metastases or CNS disease that requires increased steroid doses for control.
- •Pregnant or nursing women.
研究组 & 干预措施
Phase Ib:Vebreltinib 100mg/150mg/200mg BID + PLB1004 80mg/160mg QD
In the dose-escalation and dose-expansion phase, patients received oral Vebreltinib 100mg/150mg/200mg BID plus PLB1004 80mg/160mg once daily.
干预措施: Vebreltinib (Drug)
Phase Ib:Vebreltinib 100mg/150mg/200mg BID + PLB1004 80mg/160mg QD
In the dose-escalation and dose-expansion phase, patients received oral Vebreltinib 100mg/150mg/200mg BID plus PLB1004 80mg/160mg once daily.
干预措施: PLB1004 (Drug)
Phase II:Cohort 1
In phase II-Cohort 1:Failed first-generation or second-generation EGFR inhibitors, negative T790M mutation and c-Met amplification(GCN≥6).Patients received oral Vebreltinib（RP2D）plus PLB1004 （RP2D）.
干预措施: Vebreltinib (Drug)
Phase II:Cohort 1
In phase II-Cohort 1:Failed first-generation or second-generation EGFR inhibitors, negative T790M mutation and c-Met amplification(GCN≥6).Patients received oral Vebreltinib（RP2D）plus PLB1004 （RP2D）.
干预措施: PLB1004 (Drug)
Phase II:Cohort 2
In phase II-Cohort 2 :Failed third-generation EGFR inhibitors, c-Met amplification(GCN≥6).Patients received oral Vebreltinib（RP2D）plus PLB1004 （RP2D）.
干预措施: Vebreltinib (Drug)
Phase II:Cohort 2
In phase II-Cohort 2 :Failed third-generation EGFR inhibitors, c-Met amplification(GCN≥6).Patients received oral Vebreltinib（RP2D）plus PLB1004 （RP2D）.
干预措施: PLB1004 (Drug)
Phase II:Cohort 3
In phase II-Cohort 3 :Failed first-generation or second-generation EGFR inhibitors, c-Met over expression.Patients received oral Vebreltinib（RP2D）plus PLB1004 （RP2D）.
干预措施: Vebreltinib (Drug)
Phase II:Cohort 3
In phase II-Cohort 3 :Failed first-generation or second-generation EGFR inhibitors, c-Met over expression.Patients received oral Vebreltinib（RP2D）plus PLB1004 （RP2D）.
干预措施: PLB1004 (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities (DLT) as defined in the protocol.
时间窗: 28 days
In phase Ib，Number of patients with at least 1 dose-limiting toxicity (DLT), which is any toxicity defined as a DLT in the Clinical Study Protocol
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).
时间窗: 3 years
In phase Ib，Incidence of Treatment-Emergent Adverse Events (TEAEs),
Overall Response Rate (ORR）
时间窗: 3 years
In phase II,ORR is defined as the proportion of subjects with confirmed best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1.
次要结局
- Pharmacokinetics of Vebreltinib and PLB1004: Maximum plasma concentration of the study drug (C-max)(From date of first dose up until 28 days post last dose)
- Pharmacokinetics of Vebreltinib and PLB1004: Time to maximum plasma concentration of the study drug (T-max)(From date of first dose up until 28 days post last dose)
- Incidence of Treatment-Emergent Adverse Events(3 years)
- Pharmacokinetics of Vebreltinib and PLB1004 : Area under the concentration time curve (AUC)(From date of first dose up until 28 days post last dose)