Inclusion Criteria:
1. According to the 8th edition of the AJCC/UICC TNM staging system for NSCLC, patients with locally advanced (stage III B/III C), metastatic or recurrent (stage IV) NSCLC confirmed by histology or cytology who are unable to undergo surgery and radical concomitant radiochemotherapy and are confirmed to have at least one measurable lesion according to RECIST 1.1.
2. KRAS mutation positive detected by ARMS or NGS;
3. Have been treated with 1st line of standard therapy and experienced disease progression;
4. Patients who were assessed as CR, PR, or SD (reduction) after being treated with 2 cycles of anlotinib and trametinib.
5. No active brain metastases;
6. Age ≥18 years and ≤75 years;
7. ECOG PS score: 0 to 2;
8. Palliative radiotherapy must be completed 7 days before the first dose of study drug is administered;
9. The main organs function is normal, that is, the following criteria met:
10. Good hematopoietic function, defined as absolute neutrophil count ≥1.5×10\^9 /L, platelet count≥100 ×10\^9 /L, hemoglobin ≥90g/L \[no blood transfusion or no erythropoietin (EPO) dependence within 7 days before enrollment\]
11. Biochemical test results should meet the following criteria: BIL \< 1.25 times the upper limit of normal value (ULN); ALT and AST \< 2.5 × ULN; in case of liver metastases, ALT and AST \< 5 × ULN; Cr ≤1.5×ULN or creatinine clearance (CCr) ≥60ml/min; Coagulation function is good, INR and PT ≤1.5 times ULN; if the subject is receiving anticoagulant treatment, PT should be within the prescribed range of use of anticoagulant drugs;
12. Women of child-bearing age should agree to take contraceptive measures (such as intrauterine devices, contraceptives or condoms) during the study and within 6 months after the study; non-breast-feeding patients whose serum or urinary pregnancy test should be negative; male patients should agree to take contraceptive measures during the study and within 6 months after the study.
13. Patients are voluntarily enrolled into the study, sign the informed consent form and have good compliance.
Exclusion Criteria:
1. Small cell lung cancer (including mixed small cell and non-small cell lung cancer);
2. Patients who have received previous treatment ≥ 4th lines of standard therapies.;
3. There are obvious bleeding symptoms or active autoimmune disease;
4. Patients with other driver mutation.
5. Patients with many factors affecting oral medication, such as dysphagia, gastrointestinal resection, chronic diarrhea and intestinal obstruction;
6. Patients who are known to have active brain metastases, spinal cord compression, carcinomatous meningitis, or brain or leptomeningeal disease diagnosed by CT or MRI at the time of screening;
7. Patients with severe and / or uncontrolled diseases, such as:
8. Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months before randomization, severe uncontrolled arrhythmias; uncontrolled blood pressure (systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg);
9. Active or uncontrolled serious infection;
10. Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis;
11. Not completely controlled eye inflammation or eye infection, or any condition that may lead to the above-mentioned ocular diseases
12. Poorly controlled diabetes (fasting blood glucose (FBG) \> 10mmol/L);
13. Routine urine test result indicates that urine protein ≥++, and 24-hour urine protein quantitation is confirmed to be \> 1.0 g;
14. Active tuberculosis, etc.;
15. Uncontrolled hypercalcemia (\> 1.5 mmol/L calcium ion or calcium \> 12 mg/dL or corrected serum calcium \> ULN), or symptomatic hypercalcemia requiring continued diphosphate therapy;
16. Long-term unhealed wounds or fractures;
17. Patients who have a history of psychotropic drug abuse and cannot abstain from it or have mental disorders;
18. Patients who are known to have severe allergies (≥ grade 3) to active ingredients and any excipients of study drugs;
19. Patients who have other malignant tumors (except radical cervical carcinoma in situ, non-melanoma skin cancer, etc.) at the same time; patients who are evaluated by the investigator to have concomitant diseases that seriously endanger the safety of the patients or affect the patients completing the study.
20. The subjects or their sexual partners cannot or refuse to take effective contraceptive measures during the clinical trial.
21. Pregnant or breast-feeding women.
22. Patients who are allergic to any medicine or any ingredient; the patients with a history of treatments involving MEK inhibitors (trametinib, selumetinib, etc.) and RTKs inhibitors (anlotinib, sorafenib, apatinib, cabozantinib, etc.) were considered ineligible.
23. Patients in other situations who are evaluated by the investigator to be ineligible to be enrolled.
