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

NCT ID: NCT06829459

Last Updated: 2025-04-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-03
• Study Completion Date: 2029-02-15

Brief Summary

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).

Conditions

Non-Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Glumetinib

Intervention Type: DRUG

Patients will be administered glumetinib 300 mg/dose once daily once daily under fasting conditions in each 21-day treatment cycle.

Osimertinib mesylate

Intervention Type: DRUG

Patients will be administered osimertinib mesylate 80 mg/dose once daily under fasting conditions in each 21-day treatment cycle.

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.

Group Type: ACTIVE_COMPARATOR

Pemetrexed

Intervention Type: DRUG

Patients will be administered pemetrexed 500 mg/m\^2 via intravenous infusion on the first day of each 3-week cycle.

Cisplatin or carboplatin

Intervention Type: DRUG

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

Interventions

Glumetinib

Patients will be administered glumetinib 300 mg/dose once daily once daily under fasting conditions in each 21-day treatment cycle.

Intervention Type: DRUG

Osimertinib mesylate

Patients will be administered osimertinib mesylate 80 mg/dose once daily under fasting conditions in each 21-day treatment cycle.

Intervention Type: DRUG

Pemetrexed

Patients will be administered pemetrexed 500 mg/m\^2 via intravenous infusion on the first day of each 3-week cycle.

Intervention Type: DRUG

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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):

1. IHC: 3 +, ≥ 90%

2. 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.

Exclusion Criteria

• 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;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai JMT-Bio Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Clinical Trials Information Group officer

Role: CONTACT

ctr-contact@cspc.cn

86-0311-69085587

Facility Contacts

Wang Jie, Ph.D

Role: primary

cancergcp@163.com

8610-87788495

Other Identifiers

SYH2065-002

Identifier Type: -

Identifier Source: org_study_id