This is an open-label, multi-center, randomized, phase III study. It is aimed to firstly evaluate the effectiveness and safety of almonertinib induction therapy in EGFR-mutated patients with unresectable stage III non-small cell lung cancer, and to evaluate the effectiveness and safety of dynamic MRD guided maintenance therapy with almonertinib after induction therapy with almonertinib and local therapy (radical surgery or radiotherapy) evaluated by MDT diagnostic model. The study includes a screening period (not more than 28 days after the subject with signed informed consent before first medication), treatment period (including induction therapy with almonertinib\ radical therapy under MDT model\ consolidation therapy with almonertinib) and follow-up period.

This is an open-label, multi-center, randomized, phase III study. It is aimed to firstly evaluate the effectiveness and safety of almonertinib induction therapy in EGFR-mutated patients with unresectable stage III non-small cell lung cancer, and to evaluate the effectiveness and safety of dynamic MRD guided maintenance therapy with almonertinib after induction therapy with almonertinib and local therapy (radical surgery or radiotherapy) evaluated by MDT diagnostic model. The study includes a screening period (not more than 28 days after the subject with signed informed consent before first medication), treatment period (including induction therapy with almonertinib\ radical therapy under MDT model\ consolidation therapy with almonertinib) and follow-up period.

Eligible subjects receive 110 mg of almonertinib once a day for 8 consecutive weeks of induction therapy; local treatment (surgical or radical radiotherapy) is selected after MDT assessment. Subjects will be randomly assigned to groups A and B. Stratification factors included EGFR 19deletion or EGFR 21L858R mutation; shedding or non-shedding ctDNA at baseline; radical surgery or radiotherapy under MDT model.

Subjects in group A will receive 110 mg of almonertinib once a day for 2 years. Imaging evaluation is conducted every 12 weeks. Subjects in group B will receive almonertinib guided by dynamic MRD monitoring. When ctDNA was positive (MRD+), subjects will receive 110 mg of almonertinib once a day for 12 weeks; when ctDNA was negative (MRD-), subjects will stop almonertinib and be observed for 12 weeks. This model will continue until disease recurrence or metastasis.

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be included in this study:

1. Over 18 years old (including 18 years old) and under 70 years old (including 70 years old).

2. The Eastern Cooperative Oncology Group (ECOG) physical status score is 0 or 1, and there is no deterioration within 2 weeks before the study drug treatment, and the expected survival period is not less than 12 weeks.

3. Stage III non-squamous cell non-small cell lung cancer confirmed by histopathology or cytology and determined by the investigator to be unresectable (International Association for the Study of Lung Cancer Eighth Edition Lung Cancer Staging).

4. Tumor tissue samples or blood samples, pleural effusions, ascites effusions, and pericardial effusions are confirmed to be EGFR sensitive mutations (ie, exon 19 deletion or L858R, alone or coexisting, Or with other EGFR mutations, but patients with EGFR20 exon insertion mutations cannot be included in the group) by laboratory tests approved by the investigator.

5. According to the RECIST1.1 standard, the subject must have at least one imaging measurable lesion. The baseline tumor imaging evaluation was performed within 28 days before the first medication.

6. Women of childbearing age should take appropriate contraceptive measures from screening to 3 months after stopping the study treatment and should not breastfeed. Before starting the administration, the pregnancy test is negative, or meeting one of the following criteria proves that there is no risk of pregnancy:

   1. Postmenopausal is defined as age greater than 50 years，and amenorrhea for at least 12 months after stopping all exogenous hormone replacement therapy.
   2. For women younger than 50 years old, if the amenorrhea is 12 months or more after stopping all exogenous hormone treatments, and the luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels are within the laboratory postmenopausal reference value range, also It can be considered postmenopausal.
   3. Have received irreversible sterilization, including hysterectomy, bilateral ovariectomy or bilateral fallopian tube resection, except for bilateral fallopian tube ligation.

7. Male subjects should use barrier contraception (ie, condoms) from screening to 3 months after the study treatment is stopped.

8. The subjects themselves participated voluntarily and signed a written informed consent form.

Exclusion Criteria:

Subjects who meet any of the following criteria cannot be included in this study:

1. Have received any of the following treatments:

   1. Have received lung surgery in the past;
   2. Have used any EGFR tyrosine kinase inhibitor in the past;
   3. Previously received any systemic chemotherapy or immunotherapy for lung cancer;
   4. Receive any lung cancer radiotherapy in the past;

2. The patient has undergone open surgery on other parts except the lungs within 14 days before using the study drug for ≤14 days.

3. In addition to NSCLC, another malignant disease has been diagnosed in the past 5 years (excluding completely resected basal cell carcinoma, bladder carcinoma in situ, and cervical carcinoma in situ).

4. Have used proprietary Chinese medicines with anti-tumor effects in the past. Those who have used proprietary Chinese medicines with anti-tumor effects but have been used for no more than 7 days and have been stopped for 2 weeks or more before the drug treatment in this study can be included in the group.

5. There are serious or uncontrollable systemic diseases (such as severe mental, neurological, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, liver or kidney disease, left ventricular ejection fraction (LVEF) < 50%, uncontrolled hypertension [that is, it is still greater than or equal to CTCAE level 3 hypertension after drug treatment]); suffering from swallowing dysfunction, active gastrointestinal disease, or other significant effects on the absorption of oral drugs, Disorders of distribution, metabolism, and excretion. Those who have had most gastrectomy operations in the past.

6. Fever and body temperature above 38℃ in the past week, or active infection with clinical significance. Active tuberculosis. Active fungal, bacterial and/or viral infections requiring systemic treatment.

7. Those who have active bleeding, new thrombotic diseases, are taking anticoagulant drugs, or have bleeding tendency;

8. The resting electrocardiogram has major clinically significant abnormalities in rhythm, conduction, or morphology, such as complete left bundle branch block, heart block above Ⅱ degree, clinically significant ventricular arrhythmia or atrial fibrillation, Unstable angina pectoris, congestive heart failure, chronic heart failure grade ≥ 2 by the New York Heart Association (NYHA).

9. Myocardial infarction, coronary artery/peripheral artery bypass or cerebrovascular accident occurred within 3 months.

10. The QT interval (QTc) of 12-lead ECG is ≥450 ms for males and ≥470 ms for females.

11. There are risk factors that lead to prolonged QT interval or risk factors that increase arrhythmia, such as heart failure, ≥CTCAE (version 4.03) 2nd degree hypokalemia (2nd degree hypokalemia is defined as: serum potassium <the lower limit of the normal value is 3.0mmol/L, and there are symptoms and needs treatment), congenital long QT syndrome, family history of long QT syndrome.

12. Any drug known to prolong the QT interval is being used within 2 weeks before the first dose.

13. Insufficient bone marrow reserve or organ function, reaching any of the following laboratory limits (no corrective treatment within 1 week before laboratory examination of blood):

    1. Absolute neutrophil count <1.5×109 / L;
    2. Platelet count <90×109 / L;
    3. Hemoglobin <90 g/L (<9 g/dL);
    4. Alanine aminotransferase> 3 times the upper limit of normal (ULN);
    5. Aspartate aminotransferase>3×ULN
    6. Total bilirubin> 1.5×ULN;
    7. Creatinine> 1.5×ULN or creatinine clearance rate <45 mL/min (calculated by Cockcroft-Gault formula);
    8. Serum albumin (ALB) <28 g/L;

14. Female subjects who are pregnant, lactating, or planning to become pregnant during the study period.

15. A history of interstitial lung disease, a history of drug-induced interstitial lung disease, a history of interstitial pneumonia requiring steroid therapy, or any evidence of clinically active interstitial lung disease.

16. Have a history of hypersensitivity to any active or inactive ingredients of Almonertinib, or to drugs with similar chemical structure to Almonertinib or in the same category as Almonertinib.

17. Any serious or uncontrolled eye disease (especially severe dry eye syndrome, dry keratoconjunctivitis, severe exposure keratitis or other diseases that may increase epithelial damage), according to the doctor's judgment, it may increase the safety risk of the subject; or patients with eye abnormalities who require surgery or are expected to require surgical treatment during the study period.

18. Use/consumption of drugs or foods that are known to have potent CYP3A4 inhibitory effects within 2 weeks, including but not limited to atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefa Oxazolone, nelfinavir, ritonavir, saquinavir, telithromycin, aceto-eandomycin, voriconazole, and grapefruit or grapefruit juice.

19. Use drugs known to have potent CYP3A4 inducing effects within 2 weeks, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin and Hypericum perforatum.

20. Use drugs that are CYP3A4 substrates (with a narrow therapeutic index) within 2 weeks, including but not limited to dihydroergotamine, ergotamine, pimozide, astemizole, cisapride, and terfenadine.

21. Have used strong P-gp inhibitors (including but not limited to verapamil, cyclosporin A, dexverapamil) within 2 weeks.

22. Subjects judged by the investigator who may not be in compliance with the research procedures and requirements, such as subjects who have a clear history of neurological or mental disorders (including epilepsy or dementia), currently suffering from mental disorders, etc. .

23. The investigator judges that there are any subjects that endanger the safety of the subject or interfere with the evaluation of the study.