Study on Savolitinib Combined With Osimertinib in Treatment of Advanced NSCLC With MET Amplification

Inclusion Criteria:

1. Fully aware this study and voluntary to sign the informed consent form, and willingand able to comply with the study procedure;

2. Age ≥ 18 and ≤75 years;

3. In accordance with the 8th Edition of TNM staging for lung cancers by InternationalAssociation for the Study of Lung Cancer and American Joint Committee on Cancer,patients with histologically or cytologically confirmed unresectable andnon-suitable for radical concurrent chemoradiotherapy, locally advanced ormetastatic (stage IIIB, IIIC or IV) NSCLC;

4. EGFR sensitive mutations prior to the first-line EGFR-TKI therapy;

5. Radiologically documented disease progression after the first-line EGFR-TKI;

6. MET amplification after disease progression following the first-line therapy;

7. Having measurable lesions (in accordance with RECIST 1. 1 criteria);

8. United States Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1;

9. Expected survival >12 weeks;

10. Adequate bone marrow reserve or organ function

11. Female patients of childbearing potential must agree to use effective contraceptivemethods from screening period to 4 weeks after discontinuation of the study drug;

12. Male subjects should be willing to agreement to remain abstinent (refrain fromheterosexual intercourse) or use contraceptive measures and agreement to refrainfrom donating sperm. ;

13. Being able to take or swallow the drug orally.

Exclusion Criteria:

1. Patients with positive T790M mutations;

2. Previous treatment for c-MET;

3. Currently having other malignant tumors, or having other infiltrating malignanttumors in the past 5 years.;

4. Previous use of systematic antitumor therapy other than EGFR-TKI for advanced NSCLC;

5. Currently having received antiangiogenic therapy or traditional Chinese medicinewith antitumor indication、extensive radiotherapy 、palliative local radiotherapy, amajor surgery,or participated in other drug clinical trials and receivedcorresponding tudy drug etc;

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. Known cancerous thrombus or deep vein thrombosis or uncontrollable hypertensiondespite the use of drugs;

12. Mean resting corrected QT interval (QTcF) or Any important abnormality in rhythm;

13. Presence of meningeal metastases, spinal cord compression or active brain metastasesprior to the start of study treatment;

14. Active gastrointestinal disease or other conditions significantly affecting theabsorption, distribution, metabolism or excretion of oral study drug;

15. Lack of compliance with participation in this clinical study or inability to complywith the limitations and requirements of the study, as judged by investigators;

16. Known allergy to the active or inactive ingredient of Savolitinib or Osimertinib;

17. Previous history of interstitial lung disease, drug-induced interstitial lungdisease, radiation pneumonitis and any active interstitial lung disease;

18. Pregnant or breastfeeding women;