Previous clinical studies showed there is a potential value of EGFR-TKI in local advanced EGFR-mutant NSCLC, while the risk of radiation pneumonia in combination of EGFR-TKI with thoracic radiotherapy is unknown. This study aims to explore the safety and efficacy of concurrent almonertinib, a new third-generation EGFR-TKI drug, with radiotherapy in local advanced EGFR-mutant NSCLC patients.

Doublet platinum-based therapy combined with radiotherapy remains the standard treatment for first-line management of unresectable stage III NSCLC patients, regardless of the EGFR mutation status. But the 5-year survival rate is not satisfying. Previous clinical studies showed there is a potential value but also a high risk of radiation pneumonia in treatment regimens of combination TKI with radiotherapy. This study intends to explore the safety and efficacy of concurrent almonertinib, a new third-generation EGFR-TKI drug, with radiotherapy in EGFR-sensitive mutated locally advanced NSCLC patients.

Inclusion Criteria:

• Confirmed histologically or pathologically as non-small cell lung cancer;
• According to the eighth edition of the 2015 IASLC international lung cancer staging, imaging staging assessed as inoperable stage III patients (according to the eighth edition of the 2015 IASLC international lung cancer staging);
• Blood or tissue EGFR detection is Exon 19 deletion or L858R mutation;
• Have not received systemic anti-tumor therapy;
• FEV1>0.75L;
• Age ≥ 18 years old;
• ECOG PS score ≤ 2;
• Estimated survival period ≥ 6 months;
• Women must undergo surgical sterilization, post-menopausal, or take contraceptive measures during the treatment period and within 3 months after the end;
• Sign the informed consent form.

Exclusion Criteria:

• Previously received other anti-tumor treatment, including almonertinib or other EGFR-TKI drugs;
• Contraindications for radiotherapy such as uncontrolled systemic lupus erythematosus, scleroderma or other connective tissue diseases;
• Other malignant tumors within 5 years (except for non-melanoma skin cancer and cervical cancer);
• Any medical or non-medical reasons prevent the patient from continuing to participate in the research;
• It is expected that the patient will not be able to comply with the research procedures, restrictions and requirements, and researchers determine that the patient is not suitable for participating in the trial;
• Currently receiving (or unable to stop using it before receiving the first dose of study treatment) drugs or herbal supplements known to be potent inducers of CYP3A4 (at least 3 weeks ago);
• The patient is taking any drugs that prolong the QT interval, and the drug cannot be stopped before the treatment of almonertinib;
• Patients with lung V20 > 28% even after two-month almonertinib treatment.
• Pregnancy or breastfeeding.