metastatic non-small cell lung cancer with MET exon 14 mutation
Conditions
Interventions
Monotherapy group:Oral administration of Boretinib enteric coated capsules for the treatment of 200mg BID
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.Voluntarily sign a written informed consent form to participate in the study, willing and able to comply with the relevant visits and procedures of the study; 2.Men or women aged 18 and above; 3.Patients with locally advanced or metastatic non-small cell lung cancer confirmed by histology or cytology (including lung sarcomatoid carcinoma, according to AJCC 8th edition lung cancer staging, stages IIIB-IV) (external hospital pathology reports are acceptable); 4.Perform NGS testing on tumor tissue or blood samples using CLIA or CAP certified laboratories or designated central laboratories by the applicant, and confirm the presence of MET exon 14 mutations. And patients are required to provide sufficient tumor tissue (archived or fresh samples) and blood samples for retrospective testing and analysis in the central laboratory (see laboratory manual) to support the development of accompanying diagnostic reagents required for the marketing of boratinib. Note: Patients who have received systemic anti-tumor therapy in the past are preferred to choose tumor tissue obtained after the latest anti-tumor therapy shows disease progression for biomarker detection; 5.Organizational sample testing confirms EGFR wild-type, ALK rearrangement negative, ROS1 rearrangement negative, KRAS mutation negative; 6.At least one measurable lesion (according to RECIST 1.1 criteria). For a lesion that has previously undergone radiotherapy, it can only be considered a target lesion if there is clear disease progression after radiotherapy; 7.ECOG Physical Status Score 0-1; 8.Expected survival period >= 3 months; 9.The laboratory test indicators meet the following requirements: • Aspartate aminotransferase (AST): = 75 × 10^9/L (in the absence of blood transfusion or single platelet transfusion or growth factor use within 10 days before the start of treatment) • Absolute neutrophil count: >= 1.5 × ULN 10^9/L (without the use of growth factors within 10 days before the start of treatment) • Hemoglobin>90g/L( If there is no blood transfusion or growth factor use within 10 days before the start of treatment, coagulation indicators: INR 50 mL/min, calculated using the Cockcroft Gault formula: (140 age [yr]) × body weight (kg) × 1.23 × (0.85, if female)/serum creatinine (µ mol/L), urea/urea nitrogen: <= 1.5 × ULN, asymptomatic serum amylase <= Grade 2 (NCI-CTCAE 5.0). For patients with grade 2 serum amylase abnormalities before the first dose, it must be confirmed that there are no signs and/or symptoms suggesting pancreatitis or pancreatic injury (such as elevated P-amylase, abnormal pancreatic imaging results, etc.) • Serum lipase: <= 1.5 × ULN; 10.Researchers assess good compliance and are able to complete scheduled visits, treatments, and laboratory tests according to the protocol; 11.Men and women with fertility must agree to take effective contraceptive measures from the signing of the informed consent form until 3 months after the last administration of the study drug (see Appendix 2 for details). Women with fertility must have a negative serum pregnancy test result within 7 days prior to the first study drug a
Exclusion criteria
Exclusion criteria: 1.Not willing to provide tumor tissue or blood samples for molecular testing; 2.Previously received MET inhibitors or hepatocyte growth factor (HGF) targeted therapy; 3.Symptomatic and neurologically unstable central nervous system (CNS) metastases occur, or CNS diseases that require increased steroid doses for control. Attention: CNS metastasis patients whose symptoms have been controlled can participate in this trial. Patients with symptomatic or unstable CNS metastases must have completed radiotherapy or CNS tumor metastasis surgery at least 2 weeks after treatment before entering the study. The patient's neurological function must be in a stable state, and no new neurological deficits were found in clinical examinations, and no new problems were found in CNS imaging examinations. If patients need to use steroids to treat CNS metastases, their steroid treatment dose has reached a stable level at least two weeks before signing the informed consent form; 4.Patients with clinically poorly controlled pleural, peritoneal, or pericardial effusion who have been determined by researchers to be unsuitable for inclusion; 5.Unstable or uncontrollable diseases or conditions related to or affecting cardiac function (such as unstable angina, congestive heart failure [NYHA>class II], and uncontrolled hypertension [defined as diastolic blood pressure>100 mmHg and/or systolic blood pressure>160 mmHg regardless of the use of antihypertensive drugs). Allow screening before starting or adjusting antihypertensive drugs]; 6.Having coagulation dysfunction or bleeding tendency, including a history of arterial or venous thromboembolic events (including myocardial infarction, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis or any other serious thromboembolic events) occurring within 6 months before the first study drug administration, any life-threatening bleeding events (including requiring blood transfusion therapy, surgery or local treatment, continuous drug treatment), and the researcher's judgment of bleeding tendency; 7.At rest, according to Fridericia's formula (see Appendix 5 for calculation), the average corrected QT interval (QTcF) of three electrocardiograms during the screening period is greater than 470 ms; There are risk factors that can cause QTc interval prolongation, such as chronic hypokalemia that cannot be corrected by complementary therapy, congenital or familial long QT syndrome, family history of unexplained sudden death in first-degree relatives under 40 years old, or concomitant use of any drugs known to prolong QT interval and cause apical torsion ventricular tachycardia; 8.Any significant cardiac arrhythmia such as complete left bundle branch block, second or third degree heart block, uncontrolled ventricular arrhythmias, supraventricular, nodal arrhythmias, and other cardiac arrhythmias not controlled by medication; 9.Active gastrointestinal diseases (such as ulcerative lesions, uncontrolled nausea, vomiting, diarrhea, and absorption disorders) or other conditions (such as inability to swallow the test drug, or previous major gastrointestinal surgery) significantly affect the absorption, distribution, metabolism, or excretion of the oral study drug; 10.Active infection exists, including but not limited to: 1) hepatitis B B (hepatitis B B surface antigen [HBsAg] positive and hepatitis B virus [HBV] DNA >= 500 IU/ml), hepatitis C (anti hepatitis C virus [HCV] antibody and HCV-RNA are po
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective relief rate evaluated by IRC; | — |
Secondary
| Measure | Time frame |
|---|---|
| DCR evaluated by IRC and ORR and DCR confirmed by researcher evaluation; | — |
Countries
China
Contacts
Public ContactJinji Yang
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Outcome results
None listed