Efficacy and Safety of Almonertinib Combined With Stereotactic Body Radiotherapy (SBRT) in the Treatment of Non-small Cell Lung Cancer With EGFR Sensitive Mutation: a Single-arm, Open-label Clinical Trial

Subjects will not be enrolled in the study if they fulfil any of the following criteria:

1. Patients with postoperative recurrence.

2. Non-primary patients who have received any of the following prior treatments:

1. prior use of any EGFR tyrosine kinase inhibitor (EGFR-TKI);

2. prior radiotherapy for any lung cancer;

3. patient has undergone major surgery within 4 weeks prior to the first dose of study drug;

4. use of a strong inhibitor of CYP3A4, an inducer, or a drug with a narrow therapeutic window that is a CYP3A4-sensitive substrate within 7 days prior to the first dose of study drug.

3. Patients with other malignancies that require standardised treatment or major surgery within 2 years of the first dose of study treatment.

4. Patients who are amenable to surgical resection.

5. Patients with progression within 3 months of targeted therapy.

6. Patients with unrelieved residual toxicity from prior therapy greater than CTCAE grade 1 at the time of initiation of study treatment, with the exception of alopecia and grade 2 neurotoxicity from prior chemotherapy.

7. Patients with uncontrolled pleural effusion and/or pericardial effusion.

8. Have any serious or poorly controlled systemic disease such as poorly controlled hypertension, active bleeding prone constitution or active infection as judged by the investigator. Exclusion of chronic diseases is not required.

9. Refractory nausea, vomiting or chronic gastrointestinal disorders, inability to swallow study medication or a history of extensive bowel resection that may interfere with adequate absorption of almonertinib.

10. Cardiac findings consistent with any of the following:

1. resting electrocardiogram (ECG) examination yielding a corrected QT interval (QTc) \> 470 msec, applying the Fridericia formula for QT interval correction (QTcF);

2. resting ECG suggests the presence of a variety of clinically significant rhythmic, conduction, or ECG morphological abnormalities (e.g., complete left bundle-branch block, third-degree atrioventricular conduction).

3. presence of any factor that increases the risk of QTc prolongation or arrhythmic events, such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome, or sudden unexplained death in an immediate family member under the age of 40 years or any combination of medications that prolong the QT interval;

4. left ventricular ejection fraction (LVEF) ≤40%.

11. History of interstitial lung disease or any evidence of clinically active interstitial lung disease.

12. Inadequate bone marrow reserve or organ function at the following laboratory limits:

1. Absolute neutrophil count \< 1.5 x 10\^9 / L;

2. Platelet count \< 100 x 10\^9 / L;

3. Haemoglobin \< 90 g/L (\< 9 g/dL);

4. Alanine aminotransferase \> 2.5 times the upper limit of normal (ULN);

5. Aspartate aminotransferase \> 2.5 x ULN;

6. Total bilirubin \> 1.5 x ULN; or presence of Gilbert's syndrome (unconjugated hyperbilirubinemia);

7. Creatinine \> 1.5 x ULN and creatinine clearance \< 50 mL/min (calculated by the Cockcroft - Gault formula); confirmation of creatinine clearance is required only if creatinine \> 1.5 x ULN.

13. Women who are breastfeeding or who have had a positive blood or urine pregnancy test result within 3 days prior to the first dose of study treatment.

14. History of hypersensitivity to any active or inactive ingredient of almonertinib or to a drug with a similar chemical structure to almonertinib or an analogue of almonertinib.

15. Any serious or uncontrolled ocular pathology that, in the judgement of the physician, may increase the risk to the patient's safety.

16. Patients who, in the judgement of the investigator, may have poor compliance with the procedures and requirements of the study.

17. Patients who, in the judgement of the investigator, have any condition that jeopardises patient safety or interferes with the assessment of the study.

What this study is about