Trametinib Plus Anlotinib in Non-G12C KRAS-Mutant NSCLC Patients

Inclusion Criteria: * For inclusion in the study subjects should fulfill the following criteria: 1. According to the 8th edition of the American Journal of Critical Care (AJCC)/Union for International Cancer Control (UICC) Tumor Node Metastasis (TNM) NSCLC staging system, locally advanced (stage III B/III C), metastatic or recurrent (stage IV) NSCLC patients confirmed by histology or cytology. The NSCLC patient cannot receive surgery and radical radiotherapy, and at least one measurable lesion is confirmed according to RECIST 1.1. 2. KRAS mutation positive excluded KRASG12C mutation. 3. No active brain metastases. 4. Age ≥18 years old and ≤75 years old. 5. ECOG PS score: 0-1. 6. Patients who had previously received at least 1st-line standard therapy. Note: the treatment naïve patients who refused immunotherapy/chemotherapy at 1st-line, and willingly enrolled in the clinical trial are also eligible. Part A: advanced NSCLC patients with non-G12C mutations who have previously received standard treatment or treatment naïve. Part B: advanced NSCLC patients with non-G12C mutations who have previously received standard 1st or more treatment. 7. Palliative radiotherapy must be completed 7 days before the first dose of study drug is administered. 8. The main organs are functioning normally, that is, they meet the following standards: Good hematopoietic function, defined as absolute neutrophil count ≥1.5 billion /L, platelet count ≥100 billion/L, hemoglobin ≥90 g/L \[no blood transfusion or no erythropoietin (EPO) within 7 days before enrollment dependence\]; The biochemical test results should meet the following standards: BIL \<1.25 times the upper limit of normal (ULN); ALT and AST \<2.5×ULN; if liver metastasis occurs, ALT and AST \<5×ULN; Cr ≤1.5×ULN or creatinine clearance Rate (CCr) ≥60 ml/min; good coagulation function, International Normalized Ratio (INR) and PT ≤1.5 times of ULN; if the subject is receiving anticoagulation therapy, PT should be within the prescribed range of anticoagulation drugs; Women of childbearing age should agree to take contraceptive measures (such as intrauterine devices, contraceptives, or condoms) during the study and within 6 months after the study; the serum or urine pregnancy test of non-breastfeeding patients should be negative; male patients should agree to take contraceptive measures during the study period and within 6 months after the study. 9. The patients voluntarily participated in the study, signed an informed consent form and had good compliance. 10. The expected survive time is longer than 3 months. Exclusion Criteria: * Subjects must not enter the study if any of the following exclusion criteria are fulfilled: 1. Patients with active central nervous system metastasis are excluded. If a subject has received adequate treatment for central nervous system (CNS) metastasis at least 2 weeks before enrollment, and is neurologically restored to baseline levels (except for residual signs or symptoms related to CNS treatment), the subject is eligible. In addition, subjects must stop corticosteroids, or the daily dose of prednisone must be stabilized orgradually reduced to ≤10 mg (or equivalent dose). 2. Small cell lung cancer (including mixed small cell and non-small cell lung cancer) or hollow central squamous cell carcinoma. 3. There are obvious bleeding symptoms. 4. Patients who have previously received MEK inhibitors, anlotinib or other multi-targeted anti-angiogenic therapy. 5. Patients with dysphagia, gastrointestinal resection, chronic diarrhea, intestinal obstruction and other factors that affect oral medication. 6. Patients who are known to have active brain metastases, spinal cord compression, cancerous meningitis, brain or soft tissue diseases diagnosed by computed tomography (CT) or magnetic resonance imaging (MRI) at the time of screening. 7. Patients with severe and/or uncontrollable diseases, such as: unstable angina, symptomatic congestive heart failure, myocardial infarction within 6 months, severe uncontrollable arrhythmia; uncontrolled blood pressure (BP, constriction BP \> 140 mmHg, diastolic BP \> 90 mmHg). 8. Active or uncontrolled serious infections. 9. Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis. 10. Incomplete control of eye inflammation or eye infection, or any condition that may cause the above eye diseases. 11. Poor diabetes control (fasting blood glucose (FBG) \> 10 mmol/L). 12. Routine urine test results show that urine protein is ≥++, and the 24-hour urine protein quantitative is\> 1.0 g. 13. Active tuberculosis. 14. Uncontrollable hypercalcemia (calcium ion\> 1.5 mmol/L or calcium\> 12 mg/dL or corrected serum calcium \>ULN), or symptomatic hypercalcemia that requires continued bisphosphonate therapy. 15. Long-term unhealed wounds or fractures. 16. Those who have a history of psychotropic drug abuse and cannot be quit or have mental disorders. 17. Patients with known severe allergies (≥Grade 3) to active ingredients and excipients. 18. Patients who also suffer from other malignant tumors (except radical cervical carcinoma in situ, non-melanoma skin cancer, etc.); patients who have been assessed by the investigator as having concomitant diseases that seriously endanger the patient's safety or affect the patient's completion of the study. 19. During the clinical trial, the subjects or their sexual partners cannot or refuse to take effective contraceptive measures. 20. Pregnant or breastfeeding women. 21. Previous treatment including Chinese medicine treatment. 22. Patients who are allergic to any medicine or any ingredient. 23. In other cases, patients who are not eligible for inclusion as assessed by the investigator. 24. The expected survive time is shorter than 3 months.