TY-9591 in the Patients With EGFR Mutations in Advanced NSCLC With Brain Metastases

Inclusion Criteria:

1. Male or female aged ≥18 years and <80 years.

2. Patients diagnosed with NSCLC by histology or cytology, with brain metastases.

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. Stable brain metastases that do not require immediate or planned local treatment forit during the study period.

6. At least one measurable lesion according to Response Evaluation Criteria in SolidTumours (RECIST) version 1.1.

7. The ECOG score is 0-1, and there is no deterioration 2 weeks before the study, andthe expected survival is not less than 3 months.

8. Adequate bone marrow reserve function, and no liver, kidney and coagulationdysfunction.

9. Male patients and female patients of reproductive age should take adequatecontraceptive measures from signing informed consent to 3 months after the laststudy drug treatment; Women of childbearing age have negative pregnancy test resultswithin 7 days of the first dose.

10. Patients having recovered from all grade ≤ 1 toxicities related to previousanticancer therapies (CTCAE v 5.0) except for alopecia, platinum-therapy-relatedneuropathy (where ≤2 is allowed) before first dose of study treatment.

11. Patients can understand and voluntarily sign the informed consent form.

12. 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 targetedtherapy, biotherapy and immunodrug therapy, etc.)；

4. Previous treatment with standard chemotherapy with 28 days before the firstdose of the study drug, and traditional Chinese medicine antitumor therapywithin 7 days before the first dose of the study drug;

5. Previous whole brain radiation therapy (WBRT); Receiving radiation to more than 30% of the bone marrow or with a wide field of radiation that had to becompleted within 28 days of the first dose of study treatment; Radiotherapywith a limited field of radiation within 7 days of the first dose of studytreatment or palliative radiation therapy for bone metastasis;

6. Uncontrollable or poorly controlled pleural, abdominal and pericardialeffusion;

7. Uncontrollable cancerous pain; Anesthetic painkillers did not reach a stabledose at the time of enrollment;

8. Major surgery within 28 days of the first dose of study treatment;

9. 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;

10. Patients who are receiving and need to continue receiving medications duringthe study that are known to prolong the QTc interval or may cause tachycardia;

11. Participants in other clinical trials (other than non-interventional clinicaltrials) within 28 days prior to the first administration of the investigationaldrug.

12. Patients with primary malignant brain tumors and unstable brain metastases.

13. Patients who have had or have a history of other malignancies within the past 5years (except cured basal cell or squamous cell carcinoma of the skin, papillarycarcinoma of the thyroid gland, carcinoma in situ of the cervix, and ductalcarcinoma in situ of the breast).

14. The patient had symptoms of spinal cord compression caused by the tumor.

15. Clinically severe gastrointestinal dysfunction may affect the ingestion, transportor absorption of the study drugs.

16. Cardiac function and disease are consistent with the following:

17. Corrected QT interval(QTc)> 470 milliseconds from 3 electrocardiograms (ECGs);

18. Any clinically important abnormalities in rhythm;

19. Any factors that increase the risk of QTc prolongation;

20. Left ventricular ejection fraction (LVEF) <50%.

21. 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.

22. Previous history of interstitial lung disease(ILD) or drug-induced ILD or radiationpneumonitis require steroid treatment, or any evidence of clinically active ILDdiseases.

23. Previous allogeneic bone marrow transplant.

24. Pregnant or lactating women.

25. Any other disease or medical condition that is unstable or may affect the safety orstudy compliance.

26. Hypersensitivity to TY-9591 or similar compounds or excipients.