Glumetinib Combined With Osimertinib Treatment for Non-Small Cell Lung Cancer Patients

A Multicenter Phase II/III Clinical Study on the Efficacy and Safety of Glumetinib Combined With Osimertinib as First-Line Treatment in Non-Small Cell Lung Cancer Patients With Classical EGFR Mutations Accompanied by MET Amplification or Overexpression

To evaluate the efficacy and safety of glumetinib combined with osimertinib as the first-line treatment for locally advanced or metastatic NSCLC.

Study Overview

• Status: Not yet recruiting
• Conditions: Recurrent or Metastatic NSCLC Patients With Classical EGFR Mutations Accompanied by MET Amplification or Overexpression
• Intervention / Treatment: Drug: Glumetinib Tablets; Drug: Osimertinib Mesylate Tablets; Drug: Glumetinib Tablets Placebo

Detailed Description

In the Phase II stage, eligible subjects who have passed screening will be randomly assigned in a 1:1:1 ratio into the Group 1, Group 2, and Group 3 to receive study treatment:

In the Phase III stage, eligible subjects who have passed screening will be randomly assigned in a 1:1 ratio into the test group and the control group to receive the study treatments, and the RP3D obtained from Phase II will be used as the dose of glumetinib for the test group.

Randomization stratification factors include: c-MET status (≥2+, ≥75% and 3+, <50% vs 3+, ≥50% or FISH positive), and EGFR-sensitive mutation type (19Del vs L858R).

In both the Phase II and Phase III stages, each treatment cycle is every 3 weeks, with continuous treatment until progressive disease (PD) confirmed by the investigator, intolerable toxicity, withdrawal of informed consent by the subject, loss to follow-up, death, or other criteria for terminating treatment as specified in the protocol, whichever occurs first.

• Study Type: Interventional
• Enrollment (Estimated): 390
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Group officer; Phone Number: 031169085587; Email: ctr-contact@cspc.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Able to understand and voluntarily sign the written informed consent form (ICF); 2. Male or female subjects aged 18 to 75 years (inclusive). 3. Patients with NSCLC who have unresectable locally advanced or metastatic disease; 4. At least one measurable lesion, as defined by RECIST 1.1 criteria; 5. ECOG performance status of 0 or 1; 6. Expected survival ≥ 3 months; 7. Adequate function of major organs and bone marrow; 8. Women or man of childbearing potential must use highly effective contraception.

Exclusion Criteria:

1. Prior treatment with an EGFR inhibitor or MET inhibitor;
2. Patients with metastases to meninges; with spinal cord compression; symptomatic and unstable brain metastasis;
3. Patients who have taken strong inducers or inhibitors of CYP3A4 within 2 weeks prior to the first dose of the study drug, or who cannot discontinue the use of strong CYP3A4 inducers and inhibitors during the study;
4. Patients with a history of autoimmune diseases, a history of immunodeficiency, including positive for HIV, or other acquired or congenital immunodeficiency diseases, or a history of organ transplant;
5. Presence of active infection (e.g., subjects are receiving anti-infection therapy);
6. Severe or uncontrolled cardiovascular disorder requiring treatment;
7. Refractory nausea, vomiting, chronic gastrointestinal disease, inability to swallow drugs orally;
8. Women who are pregnant or breastfeeding;

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glumetinib（200 mg） + Osimertinib; Group 1: Glumetinib 200 mg oral QD + Osimertinib 80 mg oral QD.	Drug: Glumetinib Tablets; An ATP competitive, highly selective MET receptor tyrosine kinase inhibitor; Drug: Osimertinib Mesylate Tablets; 3rd EGFR-TKI
Experimental: Glumetinib（300mg） + Osimertinib; Group 2: Glumetinib 300 mg oral QD + Osimertinib 80 mg oral QD;	Drug: Glumetinib Tablets; An ATP competitive, highly selective MET receptor tyrosine kinase inhibitor; Drug: Osimertinib Mesylate Tablets; 3rd EGFR-TKI
Experimental: Osimertinib; Group 3: Osimertinib 80 mg oral QD.	Drug: Osimertinib Mesylate Tablets; 3rd EGFR-TKI; Drug: Glumetinib Tablets Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase 2：ORR as assessed by IRC	Up to approximately 30 months after the first participant is enrolled

Secondary Outcome Measures

Outcome Measure	Time Frame
Phase 2：ORR as assessed by investigator	Up to approximately 30 months after the first participant is enrolled
phase 2：PFS as assessed by IRC and investigator	Up to approximately 30 months after the first participant is enrolled
Phase 3：PFS as assessed by invetigator	Up to approximately 30 months after the first participant is enrolled
Phase 3：ORR as assessed by IRC and investigator	Up to approximately 30 months after the first participant is enrolled
phase 2/3：OS	Up to approximately 30 months after the first participant is enrolled
phase 2/3：DCR as assessed by IRC and investigator	Up to approximately 30 months after the first participant is enrolled
phase 2/3：DoR as assessed by IRC and investigator	Up to approximately 30 months after the first participant is enrolled
phase 2/3：TTR as assessed by IRC and investigator	Up to approximately 30 months after the first participant is enrolled
phase 2/3：Frequency and severity of AEs (NCI CTCAE 5.0)	Up to approximately 30 months after the first participant is enrolled
phase 2/3：PK parameters: The plasma concentration of glumetinib	Up to approximately 30 months after the first participant is enrolled
phase 2/3：Biomarkers: c-MET expression and amplification levels, tumor-related gene mutations	Up to approximately 30 months after the first participant is enrolled

Collaborators and Investigators

• Sponsor: Shanghai JMT-Bio Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): January 31, 2030

Study Registration Dates

• First Submitted: March 27, 2025
• First Submitted That Met QC Criteria: March 27, 2025
• First Posted (Actual): April 3, 2025

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: March 27, 2025
• Last Verified: March 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; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Osimertinib
• Other Study ID Numbers: SYH2065-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No