Clinical Study on Savolitinib + Osimertinib in Treatment of EGFRm+/MET+ Locally Advanced or Metastatic NSCLC

Inclusion Criteria:

1. Fully aware of this study and voluntary to sign the informed consent form, and beingwilling 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 theInternational Association for the Study of Lung Cancer and American Joint Committeeon Cancer, and patients with histologically or cytologically confirmed unresectablelocally advanced (stage ⅢB/ⅢC), metastatic or recurrent (stage IV) NSCLC who are notsuitable 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 contraceptivemethods from screening period to 4 weeks after discontinuation of the study drug 11.Male patients whose sexual partners are women of childbearing potential must usecondoms during sexual intercourse during the study and within 6 months afterdiscontinuation of study drug

11. 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 malignanttumors in the past 5 years

3. Antitumor therapy within 2 weeks prior to the start of study treatment, includinghormone therapy, biotherapy, immunotherapy or the traditional Chinese medicine forantitumor 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 localradiotherapy within one week prior to the start of study treatment, or the aboveadverse reactions of radiotherapy did not recover;

5. Having received a major surgery within 4 weeks prior to the start of study treatmentor a minor surgery (except biopsy, and venous catheterization) within one week priorto the start of study treatment;

6. Currently receiving the potent CYP3A4 inducers or potent CYP1A2 inhibitors withintwo weeks prior to the start of study treatment;

7. Having not been sufficiently recovered from the toxicity and/or complicationresulting 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 ischemicattack;

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 ≥2weeks after receiving treatment with low molecular weight heparin (LMWH) oranalogues with similar efficacy can be enrolled;

14. Any important abnormality in rhythm

15. Presence of meningeal metastasis, spinal cord compression or active brain metastasisprior 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 complywith 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 orinactive ingredient of Savolitinib or Osimertinib; 20. Previous history ofinterstitial lung diseases, drug-induced interstitial lung diseases, radiationpneumonitis requiring glucocorticoid therapy and any active interstitial lungdiseases; 21. Pregnant and lactating women; 22. Any other disease, metabolicabnormality, physical examination abnormality or laboratory examination abnormality,certain disease or state, based on which there is a reason to suspect that thesubject is not suitable for the study drug, or one condition that will affectintepretaton of the study results or put the subject at high risk.