Evaluating glumetinib and osimertinib for lung cancer after EGFR-TKI resistance

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

This study is testing if a new combination of glumetinib and osimertinib can help people with lung cancer who have stopped responding to previous treatments.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 350 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shanghai JMT-Bio Inc. (industry)
• Drugs / interventions: gefitinib, erlotinib, icotinib, afatinib, dacomitinib, osimertinib, chemotherapy, immunotherapy, glumetinib
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06829459 on ClinicalTrials.gov

What this trial studies

This Phase III clinical study aims to assess the efficacy and safety of glumetinib combined with osimertinib mesylate compared to platinum-based doublet chemotherapy in patients with non-small cell lung cancer (NSCLC) who have developed resistance to EGFR-TKIs. Approximately 350 patients with confirmed MET amplification and/or overexpression will be enrolled and randomized into two groups for treatment. The study will utilize a central randomization system to ensure unbiased allocation of participants to either the investigational or control group. The primary focus is on patients who have previously shown disease progression after EGFR-TKI therapy.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with unresectable locally advanced or metastatic NSCLC and documented resistance to EGFR-TKIs.

Not a fit: Patients with small cell components or neuroendocrine carcinoma components in their lung cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for NSCLC patients who have become resistant to standard EGFR-TKI therapies.

How similar studies have performed: Other studies have shown promise in targeting MET amplification in NSCLC, but this specific combination approach is relatively novel.

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;

Where this trial is running

Beijing, Beijing Municipality

• Cancer Hospital Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Clinical Trials Information Group officer

Conditions: Non-Small Cell Lung Cancer