Inclusion Criteria:
1. Fully aware of this study and voluntary to sign the informed consent form, and being willing and able to comply with the study procedure;
2. Age ≥ 18
3. In accordance with the Eighth Edition of TNM Staging of Lung Cancer by the International Association for the Study of Lung Cancer and American Joint Committee on Cancer, and patients with histologically or cytologically confirmed unresectable locally advanced (stage ⅢB/ⅢC), metastatic or recurrent (stage IV) NSCLC who are not suitable for radical concurrent chemoradiotherapy;
4. Carrying two common EGFR mutations clearly related with the sensitivity to EGFR-TKI (i.e., exon 19 deletion, and L858R) and c-MET overexpression
5. Having measurable lesions (in accordance with RECIST 1.1 criteria);
6. ECOG Performance Status score 0 or 1, or Karnofsky score ≥80;
7. Survival is expected to exceed 12 weeks;
8. No any previous systematic antitumor therapy for advanced/metastatic disease;
9. adequate bone marrow reserve or organ function
10. Female patients of childbearing potential must agree to use effective contraceptive methods from screening period to 6 weeks after discontinuation of the study drug , and agree not to donate ova (oocytes) for reproductive purposes during this period;
11. Male patients whose sexual partners are women of childbearing potential must use condoms during sexual intercourse during the study and within 6 months after discontinuation of study drug
12. Being able to take or swallow the drug orally.
Exclusion Criteria:
1. Previous treatment with EGFR inhibitors or MET inhibitors;
2. Currently having other malignant tumors, or having other infiltrating malignant tumors in the past 5 years;
3. Antitumor therapy within 2 weeks prior to the start of study treatment, including hormone therapy, biotherapy, immunotherapy or the traditional Chinese medicine for antitumor indication;
4. Having received extensive radiotherapy (including radionuclide therapy, e.g., Sr-89) within 4 weeks prior to the start of study treatment or palliative local radiotherapy within one week prior to the start of study treatment, or the above adverse reactions of radiotherapy did not recover;
5. Having received a major surgery within 4 weeks prior to the start of study treatment or a minor surgery (except biopsy, and venous catheterization) within one week prior to the start of study treatment;
6. Currently receiving the potent CYP3A4 inducers or potent CYP1A2 inhibitors within two weeks prior to the start of study treatment;
7. Having not been sufficiently recovered from the toxicity and/or complication resulting from any interventional measure prior to the start of treatment;
8. Clinically significant active infection, including but not limited to tuberculosis, human immunodeficiency virus (HIV) infection (positive HIV1/2 antibody);
9. Active hepatitis B, or active hepatitis C;
10. Acute myocardial infarction, unstable angina pectoris, stroke or transient ischemic attack;
11. Uncontrollable hypertension despite the use of drugs,
12. Mean resting corrected QT interval (QTcF) or Any important abnormality in rhythm;
13. Patients whose known cancerous thrombus or deep vein thrombosis are stable for ≥2 weeks after receiving treatment with low molecular weight heparin (LMWH) or analogues with similar efficacy can be enrolled;
14. Any important abnormality in rhythm
15. Presence of meningeal metastasis, spinal cord compression or active brain metastasis prior to the start of study treatment.
16. Known allergy to the active or inactive ingredient of Savolitinib or Osimertinib;
17. Lack of compliance with participation in this clinical study or inability to comply with the limitations and requirements of the study, as judged by investigators;
18. Having participated in other drug clinical trials and received the study drug within 3 weeks prior to the start of study treatment;
19. Known allergy to the active or inactive ingredient of Savolitinib or Osimertinib;
20. Previous history of interstitial lung diseases, drug-induced interstitial lung diseases, radiation pneumonitis requiring glucocorticoid therapy and any active interstitial lung diseases;
21. Pregnant and lactating women;
22. Any other disease, metabolic abnormality, physical examination abnormality or laboratory examination abnormality, certain disease or state, based on which there is a reason to suspect that the subject is not suitable for the study drug, or one condition that will affect intepretaton of the study results or put the subject at high risk.
23. History of cirrhosis of any etiology and clinical stage; or other severe liver disease or chronic disease with severe liver involvement.
