Almonertinib Treats Advanced NSCLC Patients With EGFR Mutations Who Are Safety Intolerant After Osimertinib Treatment

Inclusion Criteria:

1. Over 18 years old (including 18 years old) and under 75 years old (including 75 yearsold)
2. Histologically or cytologically diagnosed as locally advanced or metastatic NSCLC.
3. The CTCAE ≥ grade 3 AE related to osimertinib treatment in previous treatment withosimertinib, or platelet count <75×109 / L (≥CTCAE grade 2), white blood cell count <3×109 / L (≥ CTCAE grade 2), total bilirubin> 1.5×ULN (≥CTCAE grade 2), transaminase (ALT/AST)>3.0×ULN (≥CTCAE grade 2), and the toxic reaction has been alleviated orrestored to ≤CTCAE grade 1 patient.
4. Tumor tissue samples diagnosed as locally advanced or metastatic NSCLC are confirmedto be EGFR sensitive mutations (including exon 19 deletion or L858R, both alone orcoexist with other EGFR mutations). If the tumor tissue is accessible, it isrecommended to send the tumor tissue for examination; if the tumor tissue is notaccessible or the patient cannot accept a tissue biopsy, a blood sample is alsoacceptable.
5. The Eastern Cooperative Oncology Group (ECOG) physical status score is 0 to 1, and ithas not deteriorated in the previous 2 weeks, and the minimum expected survival is 12weeks.
6. The patient has at least one tumor lesion that can be accurately measured at baseline,and the longest diameter at baseline is ≥10 mm (if it is a lymph node, the shortdiameter is required to be ≥15 mm). The selected measurement method is suitable foraccurate repeat measurement, which can be computed tomography (CT) or magneticresonance scan (MRI). If there is only one measurable lesion, it can be accepted asthe target lesion, and a baseline assessment of the tumor lesion should be performedat least 14 days after the diagnostic biopsy.
7. Women of childbearing age should take appropriate contraceptive measures fromscreening to 3 months after stopping the study treatment and should not breastfeed.Before starting the administration, the pregnancy test is negative, or meeting one ofthe following criteria proves that there is no risk of pregnancy:
8. Postmenopausal is defined as amenorrhea for at least 12 months after the age isgreater than 50 years and all exogenous hormone replacement therapy is stopped.
9. For women younger than 50 years old, if the amenorrhea is 12 months or more afterstopping all exogenous hormone treatments, and the luteinizing hormone (LH) andfollicle stimulating hormone (FSH) levels are within the laboratorypostmenopausal reference value range, also It can be considered post-menopausal.
10. Have received irreversible sterilization, including hysterectomy, bilateralovariectomy or bilateral fallopian tube resection, except for bilateral fallopiantube ligation.
11. Male patients should use barrier contraception (i.e. condoms) from screening to 3months after stopping the study treatment.
12. The subjects themselves participated voluntarily and signed an informed consent formin writing.

Exclusion Criteria:

1. Have received any of the following treatments:
2. Have previously received any EGFR tyrosine kinase inhibitor treatment exceptosimertinib;
3. The patient had undergone major surgery within 4 weeks before the firstadministration;
4. Accept other test drugs, and within 5 half-lives;
5. Within 7 days before the first administration of the study drug, CYP3A4 stronginhibitors, inducers, or drugs with a narrow therapeutic window that are CYP3A4sensitive substrates have been used.
6. Patients with other malignant tumors who need standard treatment or major surgerywithin 2 years after the first administration of the study treatment.
7. As judged by the investigator, there are any serious or poorly controlled systemicdiseases, such as poorly controlled hypertension, active bleeding-prone constitution,or active infection. No need to check for chronic diseases.
8. Refractory nausea, vomiting or chronic gastrointestinal disease, inability to swallowstudy drugs or having undergone extensive bowel resection may affect the fullabsorption of Almonertinib.
9. A history of interstitial lung disease, a history of drug-induced interstitial lungdisease, a history of interstitial pneumonia requiring steroid therapy, or anyevidence of clinically active interstitial lung disease.
10. Meet any of the following cardiac examination results:
11. The average corrected QT interval (QTc)> 470 msec obtained from 3 ECGexaminations in the resting state, the Fridericia formula is used for QT intervalcorrection (QTcF);
12. Resting ECG suggests that there are various clinically significant rhythms,conduction or ECG morphological abnormalities (such as complete left bundlebranch block, 3 degree atrioventricular block, 2 degree atrioventricular block,and PR between Period> 250 msec);
13. There are any factors that increase the risk of QTc prolongation or arrhythmiaevents, such as heart failure, hypokalemia, congenital long QT syndrome, familyhistory of long QT syndrome, or unexplained sudden death or prolonged QT ofimmediate family members under 40 Any concomitant drugs in the interval;
14. Left ventricular ejection fraction (LVEF) ≤50%.
15. Insufficient bone marrow reserve or organ function, reaching the following laboratorylimits:
16. Absolute neutrophil count <1.5×109 / L;
17. Platelet count <100×109 / L;
18. Hemoglobin <90 g/L (<9 g/dL);
19. Alanine aminotransferase> 2.5 times the upper limit of normal (ULN)
20. Aspartate aminotransferase> 2.5×ULN
21. Total bilirubin> 1.5×ULN; or Gilbert syndrome (unconjugated hyperbilirubinemia)
22. Creatinine>1.5×ULN and creatinine clearance rate<50 mL/min (calculated byCockcroft-Gault formula); only when creatinine>1.5×ULN, creatinine clearance rateneeds to be confirmed.
23. Women who are breastfeeding or whose blood or urine pregnancy test results arepositive within 3 days before the first dose of study treatment.
24. Active fungal, bacterial and/or viral infections requiring systemic treatment.
25. Have a history of hypersensitivity to any active or inactive ingredients ofAlmonertinib or to drugs with similar chemical structure to Almonertinib or the sameclass of Almonertinib.
26. Any serious or uncontrolled eye disease may increase the safety risk of the patient asjudged by the doctor.
27. Patients who are judged by the investigator who may not comply well with theprocedures and requirements of the study.
28. The investigator judges that there are any patients with conditions that endanger thesafety of the patient or interfere with the evaluation of the study.