A Study of Vebreltinib and Platinum-Containing Double Agents in Subjects With MET-Positive

Exclusion Criteria

• •1. has participated in another therapeutic clinical trial within 28 days prior to the first study dose.
• •2. have undergone major surgery within 28 days prior to the first study dose or anticipate the need for major surgery during the study period. Diagnostic procedures such as thoracoscopic biopsy and mediastinoscopy may be enrolled 7 days after the procedure. No waiting period is required after implantable infusion port and catheter placement.
• •3. lung field or whole brain radiotherapy within 28 days prior to first study dose or palliative localized radiotherapy within 14 days prior to first study dose.
• •4. have received a proprietary Chinese medicine with an antitumor indication within 1 week prior to the first study dose. Has received local antitumor drug therapy (e.g., thoracic or abdominal perfusion, etc.) within 14 days or 5 half-lives, whichever is shorter, prior to the first study dose.
• •5. a history of another primary malignancy diagnosed or requiring treatment within the past 3 years (with the exception of localized basal cell carcinoma of the skin or squamous cell carcinoma of the skin, which has been adequately treated, or any other carcinoma in situ currently in complete remission)
• •6. toxicity from prior therapy that has not returned to ≤ Grade 1 or baseline levels (as assessed by NCI-CTCAE v5.0), except for alopecia, skin pigmentation, and any other toxicity that is assessed by the investigator to be stable and does not affect the safety of participation in this study
• •7. presence of clinically symptomatic CNS metastases. Note: Subjects with symptomatic CNS metastases may be enrolled in the study after they have been treated and their symptoms are controlled, have no lesion progression for at least 2 weeks during the Screening Period as confirmed by clinical and imaging studies, and have not had an increase in their steroid dose (\<10 mg/day of prednisolone or its equivalent) for the management of CNS symptoms in the 4 weeks prior to the first study dose.
• •8. subjects with poorly controlled clinical third space effusions, including but not limited to pleural effusions, abdominal effusions, or pericardial effusions, who, in the judgment of the investigator, are not suitable for enrollment.
• •9. presence of severe cardiovascular or cerebrovascular disease, including but not limited to:
• •* Mean QT interval (QTcF) corrected by the Fridericia formula from three ECG examinations at rest \> 470 ms.
• •* Symptomatic heart failure with a New York Heart Association (NYHA) cardiac function classification of II or higher (see Chapter 10.6).
• •* Echocardiographic (ECHO) assessment showing a baseline left ventricular ejection fraction (LVEF) below the lower limit of institutional normal (LLN) or \<50%.
• •* Any clinically significant rhythmic, conduction, or morphologic abnormality as demonstrated by resting ECG results, such as complete left bundle branch block, third-degree heart block, and ventricular arrhythmias requiring antiarrhythmic drug therapy.
• •* Presence of any factor that increases the risk of QTc prolongation or the risk of arrhythmia, such as heart failure, Severe hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or use of any comorbid medication known to prolong the QT interval within 14 days prior to the first dose of study treatment.
• •* Any of the following within 6 months prior to first study administration: myocardial infarction, severe/unstable angina, coronary artery bypass grafting, congestive heart failure, cardiomyopathy, pulmonary embolism, cerebrovascular accident, or transient ischemic attack.
• •10. the presence of serious or uncontrolled systemic disease, as judged by the Investigator, including but not limited to:
• •* Uncontrolled hypertension, defined as a systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg despite pharmacological treatment Subjects with a history of hypertension will be allowed to enroll if their blood pressure control is stable on antihypertensive therapy and within the above ranges.
• •* Current unstable or clinically significant interstitial lung disease or interstitial pneumonia, or high risk of interstitial lung disease or interstitial pneumonia (e.g., interfering with activities of daily living or requiring therapeutic intervention).
• •* Unstable or decompensated other systemic disease, deep vein thrombosis, active bleeding, etc.
• •11. presence of uncontrolled co-infections, including but not limited to:
• •\- Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. If hepatitis B surface antigen (HBsAg) positive, HBV DNA testing should be performed. If the HBV DNA test value is ≤500 IU/mL (or 2000 copies/mL), the subject is eligible to participate in the study.
• •If HCV antibody positive, HCV RNA testing should be performed. If HCV RNA is negative, the subject is eligible to participate in the study.
• •* Known human immunodeficiency virus (HIV) infection or known history of acquired immunodeficiency syndrome (AIDS).
• •* Active Syphilis positive infection.
• •* Active tuberculosis infection.
• •* Other active infection requiring systemic therapy within 14 days prior to the first study dose.
• •12. presence of dysphagia, or active gastrointestinal disease, or major gastrointestinal surgery that may interfere with the administration or absorption of Vebreltinib (e.g., refractory nausea/vomiting/diarrhea, ulcerative lesions, malabsorption syndrome, etc.).
• •13. hypersensitivity to Pertinib or its excipients, or history of allergic reaction to drugs with similar chemical or biological structure or analogs to Pertinib, or history of severe allergic reaction to Pemetrexed, Cisplatin, Carboplatin (NCI CTCAE v5.0 ≥ Grade 3).
• •14. have received any live attenuated vaccination within 30 days prior to the first study dose.
• •15. known psychiatric or substance abuse disorders that may affect study compliance.
• •16. the presence of other conditions that, in the investigator's assessment, make participation in the study inappropriate, such as participation in a study that, in the investigator's opinion, is not in the subject's best interest, or that may increase the risk of toxicity, or that may interfere with absorption, distribution, metabolism, or excretion of the study medication, or that may impair the assessment of study results, or that the subject is not able to comply with the study protocols and study limitations.