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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Glumetinib; Drug: Osimertinib mesylate; Drug: Pemetrexed; Drug: Cisplatin or carboplatin

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Group officer; Phone Number: 86-0311-69085587; Email: ctr-contact@cspc.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
      • Contact: Wang Jie, Ph.D; Phone Number: 8610-87788495; Email: cancergcp@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: Glumetinib; Patients will be administered glumetinib 300 mg/dose once daily once daily under fasting conditions in each 21-day treatment cycle.; Drug: Osimertinib mesylate; Patients will be administered osimertinib mesylate 80 mg/dose once daily under fasting conditions in each 21-day treatment cycle.
Active Comparator: 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.	Drug: Pemetrexed; Patients will be administered pemetrexed 500 mg/m^2 via intravenous infusion on the first day of each 3-week cycle.; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS as assessed by IRC	Progression-Free-Survival (PFS ) as assessed by IRC	Up to approximately 24 months after the first patient is enrolled

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR as assessed by IRC	Objective response rate (ORR) as assessed by IRC	Up to approximately 24 months after the first patient is enrolled
DCRas assessed by IRC	Disease control rate (DCR) as assessed by IRC	Up to approximately 24 months after the first patient is enrolled
DOR as assessed by IRC	Duration of response (DOR) as assessed by IRC	Up to approximately 24 months after the first patient is enrolled
OS	Overall survival	Up to approximately 24 months after the first patient is enrolled

Collaborators and Investigators

• Sponsor: Shanghai JMT-Bio Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2025
• Primary Completion (Estimated): February 15, 2028
• Study Completion (Estimated): February 15, 2029

Study Registration Dates

• First Submitted: February 11, 2025
• First Submitted That Met QC Criteria: February 11, 2025
• First Posted (Actual): February 17, 2025

Study Record Updates

• Last Update Posted (Actual): April 8, 2025
• Last Update Submitted That Met QC Criteria: April 6, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Protein Kinase Inhibitors; Osimertinib; Pemetrexed; Carboplatin
• Other Study ID Numbers: SYH2065-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No