Glumetinib Combined With Osimertinib in the Treatment of Relapsed and Metastatic Non-small Cell Lung Cancer Patients Who Failed to Receive EGFR Inhibitors

Study Overview
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Brief Summary
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To explore the safety and efficacy of Glumetinib combined with Osimertinib in the treatment of relapsed and metastatic non-small cell lung cancer (NSCLC) with failed first-generation or second-generation EGFR inhibitors, negative T790M mutation and met amplification.

Detailed Description
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To explore the safety and efficacy of Glumetinib combined with Osimertinib in the treatment of relapsed and metastatic non-small cell lung cancer (NSCLC) with failed first-generation or second-generation EGFR inhibitors, negative T790M mutation and met amplification.

Official Title
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Open Label, Multicenter Phase Ib / II Study of Glumetinib Combined With Osimertinib in the Treatment of Relapsed and Metastatic Non-small Cell Lung Cancer Patients Who Failed to Receive EGFR Inhibitors

Conditions
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Negative T790M Mutation and Met Amplification

Intervention / Treatment
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* Drug: Glumetinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Can fully understand and sign informed consent form(ICF) voluntarily Male and female patients 18-80 (inclusive) years of age Stage: IIIb/IIIc/IV (AJCC version 8) ECOG Performance Status (PS): 0-1 At least one measurable lesion as per RECIST 1.1 Exclusion Criteria: Subjects with characterizedALK or ROS1 activating mutations that predict sensitivity to anti-ALK-therapy or anti-ROS1-therapy; T790 mutations is uknown or positive Patients who have symptomatic CNS metastasis which is neurologically unstable or those who have CNS disease requiring increase in the dose of steroid. (Note: Patients with controlled CNS metastasis can participate in the trial. Before entering the study, patients should have finished radiotherapy, or have received operation for CNS tumor metastasis at least two weeks before. Patients' neurological function must be in a stable state; no new neurological deficit is found during clinical examination and no new problem is found during CNS imaging examinations. If patients need to use steroids to treat CNS metastasis, the therapeutic dose of steroid should be stable for ≥3 months at least two weeks prior to entering the study.) Prior exposure to MET-directed or third generation EGFR inhibitors therapy Anticancer therapy (including chemotherapy, targeted therapy, biotherapy, hormone therapy or other investigational agents) within 4 weeks or 5 times of half-lives (whichever is shorter) prior to the first dose of the study drug or who have not recovered from the side effect of such therapy Major surgery or had significant traumatic injury within 28 days prior to the first dose of the investigational product

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Phase Ib: Glumetinib 300mg Combined With Osimertinib 80mg, Qd ,oral
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glumetinib+Osimertinib<br>The investigational product Glumetinib will be orally administrated when fasting at dose level of 300mg QD and Osimertinib will be orally administrated when fasting at dose level of 80mg QD | Drug: Glumetinib<br>* Phase Ib is a dose escalation study, the initial dose of Glumetinib is 300mg, then will be escalated to 400mg，according to the result of Phase Ib， will confirm the RP2D<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR(Objective response rate) | the sum ratio of partial response and complete response(determined by an Independent Radiology Review Committee (IRRC) according to RECIST Version 1.1) | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR(Objective response rate, assessed as per investigators) | the sum ratio of partial response and complete response(assessed as per investigators) | through study completion, an average of 1 year | 
| DOR(Duration of response) | The time from the partial response and complete response of patient to patient progressive disease or death | The time from the date of first documented partial response or complete response to progressive disease or death, an average of 6 months | 
| OS(Overall survival) | The time from the patient first dose to death | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MET amplification， T790