NSCLC
Conditions
Interventions
Experimental Group:Sunvozertinib 150 mg once daily (QD) with Glumetinib 200mg once daily
Sponsors
Jiangsu Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. be able to provide signed and dated informed consent, including adherence to the requirements and limitations listed in the Informed Consent Form (ICF) and in this protocol; 2. be = 18 years of age, male or female, at the time of signing the ICF; 3. ECOG score of 0 or 1; 4. life expectancy = 3 months; 5. patients with histologically or cytologically confirmed NSCLC diagnosed as locally advanced (Stage IIIB/IIIC), metastatic or recurrent (Stage IV) according to the International Association for the Study of Lung Cancer and the Joint Committee on the American Classification of Cancers, 8th edition of the TNM staging of lung cancer, and who are not suitable for radical surgery or concurrent radiotherapy; 6. EGFR-sensitive mutations (including exon 19 deletion, exon 21 L858R point mutation with or without exon 20 T790M mutation) confirmed by an accredited local laboratory and the patient has progressed after EGFR-TKI-targeted therapy or is intolerant to standard therapy, and needs to be treated with ositinib or other third-generation EGFR TKIs if they carry the T790M mutation. 7. MET amplification confirmed by an accredited local laboratory after treatment with a standard EGFR-TKI regimen (amplification criteria: FISH, MET GCN =5 or MET/CEP7 =2; or NGS, =20% of tumor cells, =200X sequencing depth, CNV =5; or IHC, =50% of tumor cells stained 3+); 8. at least one measurable lesion (RECIST v1.1); 9. adequate bone marrow reserve and organ system functional reserve, as summarized below: - Absolute neutrophil count (ANC) = 1.5 × 109/L, platelets = 100 × 109/L, and hemoglobin = 9 g/dL under conditions of no growth factor support or transfusion. - Total bilirubin = 1.5 × ULN; if Gilbert syndrome (unconjugated hyperbilirubinemia) is present, total bilirubin should be = 3 × ULN. - ALT and AST = 2.5 × ULN; for patients with documented liver metastases, AST and ALT levels = 5 × ULN. - Blood creatinine = 1.5 × ULN, or creatinine clearance = 50 mL/min calculated by the Cockcroft-Gault method, or urinary creatinine clearance = 50 mL/min measured over 24 hours. 10. For patients with central nervous system metastases, the following conditions must be met for enrollment: - Absence of neurological symptoms or stabilization of symptoms for at least 2 weeks with local therapy, no need for corticosteroids or antiepileptic drugs, and cessation of hormone therapy within 3 days prior to the first study drug administration; - If the brain metastatic lesion has been treated locally (radiotherapy or surgery), there should be a window of = 2 weeks prior to the first administration of study drug to ensure that adverse events related to local treatment have been reduced to CTCAE = Grade 1. 11 Women of Childbearing Potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the first dose; WOCBP or men and their WOCBP partners should agree to use effective contraception from the time of signing the ICF until 6 months after the last dose of study drug.
Exclusion criteria
Exclusion criteria: 1. histopathologically confirmed presence of a mixture of NSCLC and small cell lung cancer components; 2. patients with prior treatment with a MET inhibitor or rechallenge therapy with a prior EGFR inhibitor; 3. presence of ALK fusions, ROS1 fusions, RET rearrangements, BRAF V600E mutations, NTRK fusions, and MET ex14 jump mutation positivity; 4. a past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid hormone therapy or any clinically active interstitial lung disease, immunotherapy-induced immune pneumonitis. ; 5. the presence of spinal cord compression or meningeal metastases; 6. a history of any of the following: - Currently participating in an interventional clinical study treatment, any drug still in the developmental phase that requires a washout of 5 half-lives (or discuss with study team); - Palliative radiotherapy within 2 weeks prior to the first dose, for more than 30% of the bone marrow for radiotherapy or extensive radiotherapy, which needs to be completed within 4 weeks prior to the first dose; - Serious arterial/venous thrombotic events, including cerebrovascular accidents (e.g., history of stroke or intracranial hemorrhage), deep vein thrombosis, and pulmonary embolism, within 6 months prior to first dose; - Currently receiving (or unable to discontinue prior to first dose) a known potent inducer or potent inhibitor of CYP3A (at least 1 week prior). All subjects must avoid the combined use of drugs, herbal supplements, and foods known to be inducers/inhibitors of CYP3A within 1 week prior to dosing; - Presence of an adverse event due to prior therapy via CTCAE > Grade 1 (with the exception of any degree of alopecia) prior to the first dose; 7. diagnosis of another malignancy within 2 years prior to the first dose, except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or radically resected carcinoma in situ that has been evaluated to be clinically cured; 8. the presence of any serious or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding (e.g., hemophilia, vascular hemophilia), the presence of clinically symptomatic or recurrently draining pleural effusions, pericardial effusions, or ascites, as determined by the investigator. 9. any of the following heart-related diseases or abnormalities: - ECG at rest showing a post-calibration QTc interval (QTcF) > 470 msec - Resting ECG showing any gross abnormality in rhythm, conduction, or patterning, such as complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec - Any factor that can cause QTcF prolongation or arrhythmic disease, such as heart failure, hypokalemia, congenital QT prolongation syndrome, a family history of QT prolongation syndrome or other family history of sudden death disorders under 40 years of age, or any other condition known to cause prolongation of the QT interval - Presence of atrial fibrillation (except if drug-induced and has normalized after discontinuation of the drug). - Myocardial infarction, New York Heart Association class 2 congestive heart failure, poorly controlled arrhythmia by medication within = 6 months prior to the first dose of the drug 10. subjects with active infections, including but not limited to hepatitis B virus (HBV), hepatitis C virus (HCV) human immunodeficiency virus (HIV); (1) Active HCV and HIV infection, i.e., positive test resu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective remission rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival;Overall survival ;Duration of Response;safety; | — |
Countries
China
Contacts
Public ContactShen Bo
Jiangsu Cancer Hospital
Outcome results
None listed