Phase III Study of TY-9591 in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (FLETEO)

Inclusion Criteria:

1. Male or female aged ≥18 years and <80 years.
2. Locally advanced or metastatic NSCLC diagnosed by histology or cytology.
3. Presence of an activating EGFR-sensitive mutations (including exon 19 deletions,L858R, the above mentioned mutations alone or co-existed with other EGFR-mutatedsites).
4. No prior systemic antitumor therapy for locally advanced or metastatic NSCLC.
5. At least one measurable lesion according to Response Evaluation Criteria in SolidTumours (RECIST) version 1.1.
6. The ECOG score is 0-1, and there is no deterioration 2 weeks before the study, and theexpected survival is not less than 3 months.
7. Adequate bone marrow reserve function, and no liver, kidney and coagulationdysfunction.
8. Male patients and female patients of reproductive age should take adequatecontraceptive measures from signing informed consent to 3 months after the last studydrug treatment; Women of childbearing age have negative pregnancy test results within 7 days of the first dose.
9. Patients having recovered from all grade ≤ 1 toxicities related to previous anticancertherapies (CTCAE v 5.0) except for alopecia, platinum-therapy-related neuropathy (where ≤2 is allowed) before first dose of study treatment.
10. Patients can understand and voluntarily sign the informed consent form.
11. Patient able to comply with study requirements.

Exclusion Criteria:

1. Any of the following treatment:
2. Previous treatment with EGFR inhibitor;
3. Previous treatment with Systematic antitumor therapy (including targeted therapy,biotherapy and immunodrug therapy, etc.)；
4. Previous treatment with standard chemotherapy with 28 days before the first doseof the study drug, and traditional Chinese medicine antitumor therapy within 7days before the first dose of the study drug;
5. Receiving radiation to more than 30% of the bone marrow or with a wide field ofradiation that had to be completed within 28 days of the first dose of studytreatment; Radiotherapy with a limited field of radiation within 7 days of thefirst dose of study treatment or palliative radiation therapy for bonemetastasis;
6. Uncontrollable or poorly controlled pleural and abdominal effusion;
7. Major surgery within 28 days of the first dose of study treatment;
8. Patients currently receiving (or at least within 14 days prior to receiving thefirst dose )medications or herbal supplements known to be potent inhibitors orinducers of cytochrome P450 isoenzyme (CYP)3A4;
9. Patients who are receiving and need to continue receiving medications during thestudy that are known to prolong the QTc interval or may cause tachycardia;
10. Participants in other clinical trials (other than non-interventional clinicaltrials) within 28 days prior to the first administration of the investigationaldrug.
11. Pathologically confirmed squamous cell carcinoma or squamous cell componentpredominance in NSCLC.
12. Symptomatic brain metastases or leptomeningeal metastases.
13. Patients have spinal cord compression caused by tumor.
14. Clinically severe gastrointestinal dysfunction may affect the ingestion, transport orabsorption of the study drugs.
15. Cardiac function and disease are consistent with the following:
16. Corrected QT interval(QTc)≥ 470 milliseconds from 3 times of electrocardiograms (ECGs);
17. Any clinically important abnormalities in rhythm;
18. Any factors that increase the risk of QTc prolongation;
19. Left ventricular ejection fraction (LVEF) <50%.
20. Active human immunodeficiency virus (HIV), syphilis, hepatitis c virus (HCV) orhepatitis b virus (HBV) infection, with the exception of asymptomatic chronichepatitis b or hepatitis c carriers.
21. Previous history of interstitial lung disease(ILD), drug-induced ILD or radiationpneumonitis require steroid treatment, or any evidence of clinically active ILDdiseases.
22. Previous allogeneic bone marrow transplant.
23. Pregnant or lactating women.
24. Any other disease or medical condition that is unstable or may affect the safety orstudy compliance.
25. Hypersensitivity to investigational drug or similar compounds or excipients.