A Randomized, Controlled, Open-label Phase III Clinical Study to Evaluate the Efficacy and Safety of Glumetinib Combined With Osimertinib Mesylate Versus Platinum-based Doublet Chemotherapy in Non-Small Cell Lung Cancer Patients With MET Amplification and/or Overexpression After Resistance to EGFR-TKIs
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 350
- 试验地点
- 1
- 主要终点
- PFS as assessed by IRC
研究概览
简要总结
The is a randomized, controlled, open-label Phase III clinical study to evaluate the efficacy and safety of glumetinib combined with osimertinib mesylate versus platinum-based doublet chemotherapy in non-small cell lung cancer( NSCLC) patients with MET amplification and/or overexpression after resistance to EGFR-TKIs..
Approximately 350 NSCLC patients with MET amplification and/or overexpression after previous treatment with EGFR-TKIs are planned to be enrolled. After patients sign the informed consent form (ICF), those who are eligible for enrollment after screening examinations will be randomized to the investigational group or the control group in a 1:1 ratio by the central randomization system (IWRS).
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
- •Patients who are able to understand and voluntarily sign the written ICF;
- •Male or female patients aged ≥ 18 years (inclusive);
- •Patients with histologically or cytologically confirmed NSCLC, which is unresectable locally advanced or metastatic (Stage ⅢB, ⅢC, or Ⅳ) NSCLC according to the 8th edition of the TNM Staging System by the International Association for the Study of Lung Cancer (IASLC). Note: If the pathological type is mixed, it should be classified by primary cell type. However, if there are small cell components or neuroendocrine carcinoma components, enrollment will be not allowed;
- •Patients with EGFR-sensitive mutations confirmed by tumor histology or cytology or hematology before the first-line treatment with EGFR-TKIs;
- •Patients who have experienced documented imaging PD after treatment with first-, second- or third-generation EGFR-TKIs (gefitinib, erlotinib, icotinib, afatinib, dacomitinib, osimertinib, etc.); patients who have received prior adjuvant EGFR-TKI treatment after radical surgery may be enrolled if they have had PD within 6 months after the last dose of EGFR-TKIs.
- •Patients with PD following EGFR-TKI treatment who meet any of the following requirements: a. EGFR T790M negative with MET amplification and/or overexpression after PD following treatment with first- or second-generation EGFR-TKIs; b. MET amplification or overexpression after PD following treatment with third-generation EGFR inhibitors; MET amplification or overexpression in tumor tissue samples as confirmed by the sponsor-designated central laboratory (meeting one of the following conditions):
- •IHC: 3 +, ≥ 90%
- •FISH: GCN ≥ 5 or MET/CEP7 ratio ≥ 2
- •Patients who have at least one measurable lesion meeting the RECIST v1.1 criteria. Lesions that have previously undergone local treatments such as radiotherapy can be considered as target lesions upon confirmed progression. Brain metastases will not be considered as target lesions.
排除标准
- •Patients with prior treatment with targeted MET drugs;
- •Patients with T790M-positive mutation after PD following treatment with first- or second-generation EGFR-TKIs;
- •Patients who are positive for other driver genes, such as ALK/ROS1 positive after PD following EGFR-TKI treatment;
- •Patients with prior systemic anti-tumor therapy (including chemotherapy and immunotherapy) for advanced NSCLC other than EGFR-TKIs;
研究组 & 干预措施
Glumetinib combined with osimertinib mesylate
Patients will be administered glumetinib 300 mg/dose once daily and osimertinib mesylate 80 mg/dose once daily under fasting conditions in each 21-day treatment cycle. The treatment will continue until IRC-confirmed PD, death, intolerable toxicity, or withdrawal at the patient's discretion (whichever occurs first).
干预措施: Glumetinib (Drug)
Glumetinib combined with osimertinib mesylate
Patients will be administered glumetinib 300 mg/dose once daily and osimertinib mesylate 80 mg/dose once daily under fasting conditions in each 21-day treatment cycle. The treatment will continue until IRC-confirmed PD, death, intolerable toxicity, or withdrawal at the patient's discretion (whichever occurs first).
干预措施: Osimertinib mesylate (Drug)
Pemetrexed combined with cisplatin/carboplatin
Patients will be administered pemetrexed 500 mg/m^2 and cisplatin 75 mg/m^2 or carboplatin AUC=5 via intravenous infusion on the first day of each 3-week cycle, for a total of 4 cycles. Patients who have not experienced disease progression (PD) after completing the combination therapy will continue to receive maintenance treatment with pemetrexed following the same regimen until IRC-confirmed PD, death, intolerable toxicity, or withdrawal at the patient's discretion (whichever occurs first). Patients with IRC-confirmed PD may conditionally cross over to receive glumetinib combined with osimertinib at the discretion of the investigator and based on the patient's willingness. The end time of treatment will be determined based on the investigator's assessment of the patient's benefit from participating in the study.
干预措施: Pemetrexed (Drug)
Pemetrexed combined with cisplatin/carboplatin
Patients will be administered pemetrexed 500 mg/m^2 and cisplatin 75 mg/m^2 or carboplatin AUC=5 via intravenous infusion on the first day of each 3-week cycle, for a total of 4 cycles. Patients who have not experienced disease progression (PD) after completing the combination therapy will continue to receive maintenance treatment with pemetrexed following the same regimen until IRC-confirmed PD, death, intolerable toxicity, or withdrawal at the patient's discretion (whichever occurs first). Patients with IRC-confirmed PD may conditionally cross over to receive glumetinib combined with osimertinib at the discretion of the investigator and based on the patient's willingness. The end time of treatment will be determined based on the investigator's assessment of the patient's benefit from participating in the study.
干预措施: Cisplatin or carboplatin (Drug)
结局指标
主要结局
PFS as assessed by IRC
时间窗: Up to approximately 24 months after the first patient is enrolled
Progression-Free-Survival (PFS ) as assessed by IRC
次要结局
- DCRas assessed by IRC(Up to approximately 24 months after the first patient is enrolled)
- ORR as assessed by IRC(Up to approximately 24 months after the first patient is enrolled)
- OS(Up to approximately 24 months after the first patient is enrolled)
- DOR as assessed by IRC(Up to approximately 24 months after the first patient is enrolled)