Locally advanced or metastatic non-small cell lung cancer with EGFR mutations and MET abnormalities
Conditions
Interventions
Matched group:Osimertinib Mesylate Tablets , 80mg, once daily, PO
Test group:Vebreltinib Enteric Capsules 150mg twice daily + PLB1004 Capsules, 80mg, once daily, PO
Sponsors
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Able to understand and voluntarily sign a written informed consent document; 2.Male or female >= 18 years of age; 3.Patients with histologically or cytologically confirmed diagnosis of locally advanced (stage III.B/III.C), metastatic or recurrent (stage IV) NSCLC who cannot be treated surgically and cannot receive radical concurrent chemoradiotherapy; 4.No prior systemic anti-tumor therapy for advanced/metastatic disease; 5.Carries EGFR mutations associated with EGFR-TKI sensitivity (including exon 19 deletion and exon 21 L858R mutations); 6.C-Met overexpression confirmed by the central laboratory: by IHC detection, the staining intensity of 50% of the tumor cells in the tissue sample >= 3+; 7.Presence of at least 1 measurable lesion as assessed by RECIST 1.1 criteria; 8.ECOG performance status score of 0 or 1; 9.Estimated survival >= 3 months; 10.Laboratory tests meet the following requirements: (1) Absolute neutrophil count >=1.5×10^9/L (in the absence of growth factors within 7 days prior to the start of treatment); (2) Hemoglobin = 90g/L (in the absence of blood transfusion or use of growth factors within 7 days prior to the start of treatment); (3) Platelet count >= 75×10^9 /L (in case of no blood transfusion or use of growth factors within 7 days prior to the start of treatment); (4) Serum total bilirubin = 60 mL/min, and creatinine clearance was calculated using the Cockcroft-Gault formula: (140-age [yr]) × weight (kg) × 1.23× (0.85 if female)/serum creatinine (µmol/L); (7) International Normalized Ratio (INR) <= 1.5×ULN; h) (8) Asymptomatic serum amylase <= grade 2 (NCI-CTCAE v5.0). For patients with grade 2 serum amylase abnormalities at the start of the study, no signs and/or symptoms suggestive of pancreatitis or pancreatic injury (e.g., elevated P-amylase, abnormal pancreatic imaging results, etc.) must be confirmed (9) Serum lipase <=1.5×ULN; 11.Males of childbearing potential and females of childbearing potential (WOCBP) must agree to use effective contraception from the time of signing the informed consent form until 3 months after the last dose of study drug. Females of childbearing potential must have a negative serum pregnancy test result within <= 7 days prior to the first dose of study drug. Female subjects who have undergone sterilization or are postmenopausal are excluded.
Exclusion criteria
Exclusion criteria: 1.Known co-presence of ALK fusion positive, ROS1 fusion positive; 2.Presence of spinal cord compression, meningeal metastases, or clinically symptomatic brain metastases or need for increased steroid doses to control CNS disease at screening; Patients with symptomatic CNS metastases that have been controlled can participate in this trial (patients must be neurologically stable, no new neurological deficits found on clinical examination, and no new problems identified on CNS imaging. If the patient requires steroids to treat CNS metastases, then their dose of steroid therapy has reached a steady level for at least two weeks prior to study entry); 3.Having other malignancies (except for carcinoma in situ of any type that has been completely resected, basal cell and squamous cell skin cancer, or other tumors/cancers that have been curatively treated and have no signs of disease for at least 3 years); 4.Received one of the following treatments: (1) Prior systemic therapy for advanced tumors (patients with adjuvant or neoadjuvant chemotherapy who have local recurrence or distant metastases within 6 months of the end of treatment are considered to have received systemic therapy for advanced or metastatic NSCLC); (2) Prior treatment with EGFR-targeted therapy or c-Met inhibitor or HGF-targeted therapy; (3) Received treatment with traditional Chinese medicine or proprietary Chinese medicine with anti-tumor indication within 1 week prior to the first study drug administration; (4) Need for P-glycoprotein inducers (e.g., rifampicin) or inhibitors (e.g., ritonavir) within 1 week prior to the first dose of study drug and during the study; (5) The need for a strong inhibitor or strong inducer of cytochrome P450 3A4 enzyme (CYP3A4) within 1 week prior to the first study drug administration and during the study; (6) Extensive radiation therapy within 4 weeks prior to the first dose of study drug, or palliative local radiotherapy within 2 weeks prior to administration, or not recovering from adverse effects of radiotherapy (i.e., CTCAE 160mmHg and/or diastolic blood pressure > after treatment100mmHg), antihypertensive medications are allowed to be started or adjusted prior to screening; (2) Anti-HIV (+), or both anti-HCV and HCV-RNA (+), or HBsAg positive and HBV-DNA >= 500IU/mL (if during the screening period, HBV-DNA drops to less than 500IU/mL after receiving antiviral therapy can be enrolled, but antiviral therapy must be continued for the duration of the study; Subjects who have previously needed to receive or are receiving antiviral therapy at the time of screening must continue to receive antiviral therapy throughout the study period to be included in the study); (3) The onset of keratitis or ulcerative keratitis; (4) Active tuberculosis; (5) Active infection requiring systemic anti-infective therapy within 2 week
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety assessment;Disease control rate (DCR), Duration Of Remission (DOR), Progression Free Survival (PFS), Time to Tumor Remission (TTR), and Overall Survival (OS);Pharmacokinetic analysis;The incidence of Adverse Event /Serious Adverse Event; | — |
Countries
China
Contacts
Public ContactJinji Yang
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Outcome results
None listed