The Safety and Efficacy of First-line Lazertinib and Locally Ablative Radiotherapy in Patients With Synchronous Oligo-metastatic EGFR-mutant Non-small Cell Lung Cancer

Inclusion Criteria: 1. Histologically confirmed, treatment naïve EGFR-mutant NSCLC, with or without T790M resistance mutation. 2. Presence of the sensitising EGFR-mutation (exon 19 deletion and/or L858R) detected by an accredited laboratory. 3. Synchronous oligometastatic stage IV disease (max 5 lesions) 4. Measurable disease as defined according to RECIST v1.1 5. All lesions amenable for radical radiotherapy according to local judgment 6. Age ≥18 years 7. ECOG performance status 0-2 8. Life expectancy ≥12 months 9. Adequate haematological function: * Hemoglobin 90 g/L * Absolute neutrophil count (ANC) 1.5× 109/L * Platelet count 100× 109/L 10. Adequate renal function: Serum creatinine 1.5x ULN or creatinine clearance ≥50 mL/min (calculated according to Cockcroft-Gault, see below). Confirmation of creating clearance is only required when serum creatinine is \>1.5x ULN. 11. Adequate liver function: * ALT and AST 2.5× ULN. If the patient has liver metastases, ALT and AST must be ≤5× ULN * Total serum bilirubin 1.5× ULN. If the patient has documented Gilbert's syndrome (unconjugated hyperbilirubinaemia) 3× ULN. 12. Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test within 7 days before enrolment. 13. Written IC for protocol treatment must be signed and dated by the patient and the investigator prior to any trial-related intervention. Exclusion Criteria: 1. Prior chemotherapy, immunotherapy, radiotherapy or therapeutical surgery for NSCLC (an exception is the resection of CNS or adrenal metastases) 2. More than 5 distant oligometastases (any second intra-thoracic lesion will count as a distant metastasis; regional nodal metastases will not count to the 5 oligometastases) and more than 2 intra-thoracic lesions. 3. Brain metastases not amenable for radiosurgery or neurosurgery 4. Presence of leptomeningeal metastases 5. Symptomatic spinal cord compression 6. Extracranial metastatic locations such as malignant ascites, pleural or pericardial effusion, diffuse lymphangiosis of skin or lung, diffuse bone marrow metastasis, abdominal masses/abdominal organomegaly, identified by physical exam that is not measurable by reproducible imaging techniques. 7. Currently receiving (or unable to stop use prior to receiving the first dose of lazertinib treatment) medications or herbal supplements known to be potent CYP3A4 inducers that cannot be stopped before enrolment and for the duration of the trial. 8. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol. Patients with a resolved or chronic HBV infection are eligible if they are: * Negative for HBsAg and positive for hepatitis B core antibody \[anti-HBc IgG\] or * Positive for HBsAg, negative for HBeAg but for \>6 months have had transaminases levels below ULN and HBV DNA levels below 2000 IU/mL (i.e., are in an inactive carrier state). 9. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of lazertinib 10. Any of the following cardiac criteria: QTcF \>470 msec obtained from 3 ECGs, using the screening clinic ECG machine derived QTc value (QTcF: corrected QT interval using Fredericia's formula). Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block or second degree heart block). Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes (TdP). 11. Past medical history of ILD, drug induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD 12. Idiopathic pulmonary fibrosis which is a contraindication to lung radiation. 13. History of hypersensitivity to active or inactive excipients of lazertinib or drugs with a similar chemical structure or class to lazertinib. 14. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements Women who are pregnant or in the period of lactation. 15. Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method (Please refer to 8.4 for highly effective contraceptive methods) during the trial and up to 6 weeks for women and up to 4 months for men, after discontinuing lazertinib treatment.