Study of Metatinib Tromethamine Tablet

Inclusion Criteria:

• Patients with advanced or metastatic gastric cancer or colorectal cancer who progress after second-line therapy or the above treatment protocol, or patients with advanced or metastatic hepatocellular carcinoma who progress after first-line chemotherapy, interventional therapy or targeted therapy shall be verified by histology or cytology; or patients with advanced or metastatic non-squamous non-small cell lung cancer who cannot be operated or fail to first-line therapy shall be verified by histology or cytology;
• MET gene amplification or protein overexpression(IHC ≥2+）,or exon-14 skipping;
• At least one measurable lesion (RECIST 1.1 );
• At least 4 weeks from the last chemotherapy, radiotherapy or anti-tumor biological products treatment; at least 8 weeks from the last anti-tumor antibody products treatment; at least 6 weeks from the last dose of nitrosourea, mitomycin C or doxorubicin;
• At least 4 weeks from major surgery or trauma, and the wound should fully heal; at least 1 week from minor surgery or trauma (i.e. tissue biopsy or fine needle aspiration);
• Toxicity from previous treatment has to restore to ≤ grade 1, baseline or irreversible (NCI CTC4.0);
• ECOG performance status 0-1;
• Life expectancy ≥3 months;
• Adequate hematologic function: ANC≥1.5×10^9 /L, HB≥90g/L(blood transfusion allowed), PLT≥100×10^9/L;
• Adequate hepatic function: ALT≤3×ULN, AST≤3×ULN, TBIL≤2×ULN(patients with liver metastases or liver cancer ALT≤5×ULN, AST≤5×ULN, TBIL≤2×ULN), Child-Pugh score≤7;
• Adequate renal function: uric acid<500μmol/L, creatinine<1.7mg/dL, proteinuria≤2＋or≤2g/24h , GFR≥60 ml/min/1.73m^2;
• PT-INR/APTT≤1.5×ULN, Serum sodium, potassium, calcium, magnesium levels ≤1×ULN(NCI-CTC 4.0);
• Patients signed written informed consent;
• Willingness and capability to comply with protocol requirement and well communicate with investigators.

Exclusion Criteria:

• Severe, uncontrolled medical disorders or active infection, including but not limited to HIV antibody positive, active tuberculosis, HBV DNA copies>10^3/ml;
• Subjects have known or suspected brain metastases;
• Patients must receive other chemotherapy, targeted therapy, hormone therapy, immunotherapy, radiotherapy (except for palliative local radiation) or traditional Chinese medicine for treatment of cancer during the study;
• Previously received other VEGF/VEGFR small-molecule inhibitors or antibodies therapy, including but not limited to Bevacizumab, Ramucirumab, Aflibercept;
• Previously received other HGF/c-Met small-molecule inhibitors or antibodies therapy, including but not limited to Crizotinib, Cabozantinib, Volitinib, Capmatinib (INC280), BPI-9016M;
• Imaging showed involvement of major blood vessels or nerves by tumor;
• Uncontrolled hypertension (systolic blood pressure>150mmHg and/or diastolic blood pressure>100mmHg after treatment);
• LVEF<50%;
• Apparent heart disease, including congestive heart failure(NYHA III-IV), history of myocardial infarction, or uncontrolled angina within 6 months prior to enrollment;
• Arrhythmias need to be treated, including atrial fibrillation, supraventricular tachycardia, ventricular tachycardia or ventricular fibrillation; ECG abnormalities confirmed, including QT interval prolongation (males>450msec, females>470 msec);
• History of hemorrhagic or thrombotic events within 6 months before enrollment, i.e. cerebrovascular accidents(including TIA), pulmonary embolism, spontaneous hemorrhage of tumor;
• Patients need surgery within 28 days, or is expected to require surgery within 28 days after the last dose;
• Uncontrolled cavity effusion, such as large amount of pleural effusion and ascites;
• Gastrointestinal illnesses(i.e., uncontrolled diarrhea or malabsorption) at screening or within 3 months that may affect drug absorption;
• History or suspicious signs of gastrointestinal perforation;
• Concomitant medications that may affect the drug metabolism (i.e. strong CYP3A4 inhibitors or inducer );
• Pregnant or lactating women;
• Subjects of childbearing refused to use medically acceptable methods of contraception until 3 months after the last dose;
• Participate in other clinical trials within 4 weeks prior to enrollment;
• The investigators consider the patients are not suitable for this trial