A 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 After Resistance to EGFR-TKIs

Официальное название

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

Обзор

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).

Вмешательства

• Препарат Glumetinib
  Patients will be administered glumetinib 300 mg/dose once daily once daily under fasting conditions in each 21-day treatment cycle.
• Препарат Osimertinib mesylate
  Patients will be administered osimertinib mesylate 80 mg/dose once daily under fasting conditions in each 21-day treatment cycle.
• Препарат Pemetrexed
  Patients will be administered pemetrexed 500 mg/m\^2 via intravenous infusion on the first day of each 3-week cycle.
• Препарат Cisplatin or carboplatin
  Patients will be administered cisplatin 75 mg/m\^2 or carboplatin AUC=5 via intravenous infusion on the first day of each 3-week cycle

Первичные конечные точки

• PFS as assessed by IRC [Срок оценки: Up to approximately 24 months after the first patient is enrolled]

Вторичные конечные точки (4)

• ORR as assessed by IRC [Срок оценки: Up to approximately 24 months after the first patient is enrolled]
• DCRas assessed by IRC [Срок оценки: Up to approximately 24 months after the first patient is enrolled]
• DOR as assessed by IRC [Срок оценки: Up to approximately 24 months after the first patient is enrolled]
• OS [Срок оценки: Up to approximately 24 months after the first patient is enrolled]

Критерии участия

Критерии включения

• 1\. Patients who are able to understand and voluntarily sign the written ICF; 2. Male or female patients aged ≥ 18 years (inclusive); 3. 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; 4. Patients with EGFR-sensitive mutations confirmed by tumor histology or cytology or hematology before the first-line treatment with EGFR-TKIs; 5. 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.

6\. 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 7. 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.

Критерии исключения

• 1\. Patients with prior treatment with targeted MET drugs; 2. Patients with T790M-positive mutation after PD following treatment with first- or second-generation EGFR-TKIs; 3. Patients who are positive for other driver genes, such as ALK/ROS1 positive after PD following EGFR-TKI treatment; 4. Patients with prior systemic anti-tumor therapy (including chemotherapy and immunotherapy) for advanced NSCLC other than EGFR-TKIs;

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Cancer Hospital Chinese Academy of Medical Sciences — Пекин

Идентификаторы

NCT: NCT06829459 · SYH2065-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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