Recurrent or Metastatic NSCLC Patients With Classical EGFR Mutations Accompanied by MET Amplification or Overexpression
Conditions
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.
Interventions
An ATP competitive, highly selective MET receptor tyrosine kinase inhibitor
3rd EGFR-TKI
DRUGGlumetinib Tablets Placebo
Placebo
Sponsors
Shanghai JMT-Bio Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized, positive-controlled Phase Ⅱ/Ⅲ
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 2：ORR as assessed by IRC | Up to approximately 30 months after the first participant is enrolled |
Secondary
| Measure | Time frame |
|---|---|
| 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：ORR as assessed by 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 |
| phase 2/3：DoR as assessed by IRC and investigator | Up to approximately 30 months after the first participant is enrolled |
Contacts
Primary ContactClinical Trials Information Group officer
Outcome results
None listed