Lazertinib/Pemetrexed/Carboplatin After Osimertinib Failure in NSCLC With Brain Metastases

Inclusion Criteria:

1. Written consent A. Patients who voluntarily provided written informed consent prior to participation in the clinical trial B. Patients who voluntarily provide written informed consent for genetics and/or exploratory studies
2. Age and gender A. Male or female, 20 years of age or older B. Female patients must agree to the use of appropriate contraceptive methods and not be lactating, and for women of childbearing age, there must be evidence that the pregnancy test is negative prior to initiation of dosing, or that they are not fertile because they meet one of the following criteria at screening: box "Postmenopausal" women over the age of 50 and who are amenorrhea for at least 12 months after stopping all exogenous hormone therapy Records of irreversible surgical infertility by hysterectomy, bilateral ovariectomy, or bilateral yolk resection, tubal ligation are not permitted Women under 50 years of age had amenorrhea for at least 12 months after stopping all exogenous hormone therapy, and the levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were within the postmenopausal range of the laboratory. Is only recognized as a postmenopausal condition C. Male patients who have not undergone vasectomy must consent to the use of a blocking contraception method, i.e., condom, and sperm supply is prohibited until 3 months after taking the last investigational drug D. Must be able to swallow tablets
3. Target disease A. Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer patients. This may occur as systemic recurrence after prior surgery for early stage disease or patients may be newly diagnosed with stage IIIB/C or IV disease.

B. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2, with no deterioration in the last 2 weeks C. Life expectancy judged by the Investigator of at least 3 months D. Disease status

* Confirmed sensitizing EGFR mutation prior to administration of osimertinib (L858R, Exon 19 deletion, G719X and L861Q mutations should be confirmed as a record)
* Failure after osimertinib. Past treatment history for locally advanced or metastatic NSCLC limited to two regimen of EGFR TKI treatment (osimertinib and/or gefitinib, erlotinib, or afatinib) and/or one palliative cytotoxic chemotherapy regimen (A wash-out period of at least 2 months is required until administration after the last dose of osimertinib)
* Asymptomatic or mild symptomatic brain metastases progressed or newly confirmed patients
* One or more intracranial measurable disease in accordance with Response Evaluation Criteria in Solid Tumors (RECIST v 1.1). The target lesion that has received previous local therapy should not be considered as measurable. However, new CNS lesion after more than 3 months of previous local therapy could be considered as target lesion.

Exclusion Criteria:

* 1\) The following interventional treatment A. Prior treatment with lazertinib B. Prior treatment with investigational drugs in other clinical trials within 30 days prior to the first administration C. Patients who received cytotoxic chemotherapy for the treatment of advanced non-small cell lung cancer or other anticancer drugs other than EGFR TKI within 14 days prior to the first administration of the investigational drug D. Prior local-regional therapy within 4 weeks prior to Day 1 of trial treatment (e.g., major surgery, radiation therapy \[with the exception of palliative bone-directed radiotherapy and radiotherapy administered to superficial lesions\], hepatic arterial embolization, transcatheter arterial chemoembolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) G. Patients currently receiving drugs or herbal supplements known as inhibitors or inducers of CYP3A4 or who cannot discontinue use at least 1 week prior to the first dose of lazertinib.

H. Previous anticancer treatment-related toxicities not recovered to baseline or Grade 0-1 (except alopecia) 2) Medical history and current disease A. Symptomatic spinal cord compression (However, registration is allowed if steroid treatment is not required within at least 2 weeks before the start of administration of the investigational drug) B. Symptomatic and unstable central nervous system (CNS) or brain metastasis requiring local treatment at screening. (Asymptomatic or mild symptomatic leptomeningeal metastasis is also permitted to be registered) C. Symptomatic or intracranial bleeding that needs treatment D. History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD E. Carcinoma other than non-small cell lung cancer, if the investigator is judged to be inadequate to participate in this clinical trial due to evidence of severe or uncontrolled systemic disease, uncontrolled hypertension, or active bleeding tendency, or that it is difficult to follow this protocol. (Screening for chronic disease is not required)

F. Any of the following cardiovascular diaseases:

i. A history of congestive heart failure (CHF) of grade 3 or higher according to the New York Heart Association Classification (NYHA) or cardiac arrhythmia requiring treatment ii. A History of unstable angina or myocardial infarction experienced within 6 months before the first administration of the investigational drug iii. Left ventricular ejection fraction \<45% on recent echocardiography or MUGA scan G. Known human immunodeficiency virus (HIV) infection H. Patients with refractory nausea and vomiting, chronic gastrointestinal disorders, inability to swallow the product, or undergoing enterectomy deemed to interfere with the proper absorption of lazertinib.

I. History of hypersensitivity to drugs J. Clinically significant chronic infection or major medical or mental illness K. Subjects with any concurrent medical condition or disease that will potentially compromise the conduct of the study at the discretion of the Investigators L. History of allogeneic hematopoietic stem cell transplantation, history of whole blood transfusions that did not remove leukocytes within 120 days before the date of collection of genetics specimens 3) Criteria for cardiology and clinical laboratory testing

A. Cardiac criteria in any of the following:

i. Based on the QTc value measured with an electrocardiogram (ECG) device during screening, the average of the correction of the QT interval (QTc) at rest on an electrocardiogram (ECG) measured three times\> 470 msec ii. Clinically important abnormalities of rhythm, conduction, or shape on the ECG at rest. For example, complete left block, 3rd degree cardiac block, 2nd degree cardiac block, PR interval\> 250 msec iii. Increased risk of QTc prolongation or arrhythmia, such as heart failure, hypokalemia, congenital QT prolongation syndrome, concomitant medications known to prolong QT intervals, QT prolongation syndrome or a family history of unexplained sudden deaths under 40.

B. Laboratory index at baseline:

iv. Hemoglobin ≤ 8.0 g/dL (without transfusion or growth factor support in the preceding 14 days) v. Neutrophils \< 1.0 x 109/L vi. Platelets \< 100 x 109/L (without transfusion or growth factor support in the preceding 7 days) vii. Total bilirubin \> 3 mg/dL viii. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \> 5 x upper limit of normal (ULN) ix. Renal impairment as evidenced by serum creatinine ≥ 1.5 x ULN, or calculated creatinine clearance (CrCl) \< 50 mL/min by Cockroft-Gault formula (24-hour CrCl might be requested by the Investigator for confirmation, if calculated CrCl is \< 60 mL/min. In such case, subjects with 24-hour CrCl \< 50 mL/min should be excluded)