A Randomized, Controlled, Open Label, Multicenter Phase III Study to Evaluate the Efficacy and Safety of Vebreltinib in Combination With PLB1004 Versus Platinum-based Doublet Chemotherapy in Patients With EGFR Mutations, MET Amplification and/or Overexpression, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Following EGFR-TKI Treatment Failure
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 278
- 主要终点
- Progression-Free Survival (PFS) by BICR
研究概览
简要总结
Efficacy and Safety of Vebreltinib in Combination With PLB1004 Versus Platinum-based Doublet Chemotherapy in Patients With EGFR Mutations, MET Amplification and/or Overexpression, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Following EGFR-TKI Treatment Failure
详细描述
A Randomized, Controlled, Open Label, Multicenter Phase III Study to Evaluate the Efficacy and Safety of Vebreltinib in Combination With PLB1004 Versus Platinum-based Doublet Chemotherapy in Patients With EGFR Mutations, MET Amplification and/or Overexpression, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Following EGFR-TKI Treatment Failure
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •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).
- •At least one measurable lesion as defined by RECIST V1.
- •ECOG performance status 0 to 1.
排除标准
- •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.
- •Before randomization, patients did not recover from any toxicity and/ or complications of previous chemotherapy, surgery, radiotherapy and other anti-cancer treatments, that is, did not fall to grade 1 or lower (National Cancer Research Common Toxicity Criteria for Adverse Events [NCI-CTCAE] v5.0), except for hair loss and irrecoverable permanent radiation damage.
- •Major surgery or had significant traumatic injury within 4 weeks prior to the first dose of the investigational product.
- •Pregnant or nursing women.
研究组 & 干预措施
Vebreltinib 150mg BID plus PLB1004 80mg QD
Subjects will receive Vebreltinib 150mg orally twice per day (BID) plus PLB1004 80mg orally once per day (QD),21day cycles until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.
干预措施: Vebreltinib (Drug)
Vebreltinib 150mg BID plus PLB1004 80mg QD
Subjects will receive Vebreltinib 150mg orally twice per day (BID) plus PLB1004 80mg orally once per day (QD),21day cycles until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.
干预措施: PLB1004 (Drug)
Pemetrexed plus cisplatin/carboplatin
Subjects randomized to the control group will receive pemetrexed 500 mg/m² + platinum-based chemotherapy (carboplatin AUC 5 or cisplatin 75 mg/m²) via intravenous infusion for 4-6 cycles (determined by the investigator) as initial therapy, followed by pemetrexed maintenance therapy (500 mg/m²) until disease progression, intolerable toxicity, initiation of new antitumor therapy, death, loss to follow-up, or other treatment-terminating conditions (whichever occurred first)
干预措施: Pemetrexed plus Carboplatin or Cisplatin (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) by BICR
时间窗: 2 years
Progression-free survival (PFS) as assessed by a Blind Independent Center Review Committee (BICR) with reference to RECIST v1.1 for Solid tumors.
次要结局
- Second progression-free survival (PFS2)(2 years)
- The disease control rate (DCR)(2 years)
- Progression-Free Survival (PFS) by the investigator(2 years)
- Duration of Response (DoR)(2 years)
- Overall Survival (OS)(3 years)
- The objective response rate of the tumor (ORR)(2 years)
- The Disease Control Rate (DCR) in subjects with baseline intracranial metastases(2 years)
- Objective Response Rate (ORR) in subjects with baseline intracranial metastases(2 years)
- Assess the Quality of Healthy Living About Patients（EQ-5D-5L）(2 years)
- Duration of Response (DoR) in subjects with baseline intracranial metastases(2 years)
- Progression-Free Survival (PFS) in subjects with baseline intracranial metastases(2 years)
- Incidence of Treatment-Emergent Adverse Events(2 years)
- Plasma concentrations of Vebreltinib and PLB1004(2 years)