Clinical trial NCT06908772: Glumetinib Combined With Osimertinib Treatment for Non-Small Cell Lung Cancer Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Recurrent or Metastatic NSCLC Patients With Classical EGFR Mutations Accompanied by MET Amplification or Overexpression
Lead sponsor: Shanghai JMT-Bio Inc.
Sponsor class: INDUSTRY
First posted: 2025-04-03
Enrollment: 390
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, positive-controlled Phase Ⅱ/Ⅲ
Primary purpose: TREATMENT

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.

Eligibility criteria: 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;

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