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

Phase 2

Not yet recruiting

• Conditions: Recurrent or Metastatic NSCLC Patients With Classical EGFR Mutations Accompanied by MET Amplification or Overexpression
• Interventions: Drug: Glumetinib Tablets; Drug: Osimertinib Mesylate Tablets; Drug: Glumetinib Tablets Placebo

• Registration Number: NCT06908772
• Lead Sponsor: Shanghai JMT-Bio Inc.

Brief Summary

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

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 Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-27
• Study First Submitted QC: 2025-03-27
• Last Update Submitted: 2025-03-27
• Study Start: 2025-04-01
• Study First Posted: 2025-04-03
• Last Update Posted: 2025-04-03
• Primary Completion: 2028-12-31
• Study Completion: 2030-01-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 390

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Glumetinib（200 mg） + Osimertinib	Glumetinib Tablets	Group 1: Glumetinib 200 mg oral QD + Osimertinib 80 mg oral QD.
Glumetinib（200 mg） + Osimertinib	Osimertinib Mesylate Tablets	Group 1: Glumetinib 200 mg oral QD + Osimertinib 80 mg oral QD.
Glumetinib（300mg） + Osimertinib	Glumetinib Tablets	Group 2: Glumetinib 300 mg oral QD + Osimertinib 80 mg oral QD;
Glumetinib（300mg） + Osimertinib	Osimertinib Mesylate Tablets	Group 2: Glumetinib 300 mg oral QD + Osimertinib 80 mg oral QD;
Osimertinib	Osimertinib Mesylate Tablets	Group 3: Osimertinib 80 mg oral QD.
Osimertinib	Glumetinib Tablets Placebo	Group 3: Osimertinib 80 mg oral QD.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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：Biomarkers: c-MET expression and amplification levels, tumor-related gene mutations	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