Lazertinib & Tepotinib for EGFR Mutant NSCLC in MET Overexpressed or Amplified Who Progressed After Lazertinib Treatment

Inclusion criteria

• Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer which is not amenable to treatment with a curative aim (e.g., surgery or radiation)
• Confirmed EGFR mutations (exon 19 deletion, L858R) with acquired resistance after first-line lazertinib treatment (either partial response, complete response or stable disease last more than 6 months after initiation of Lazertinib) - patient can maintain the treatment with prior EGFR treatment as beyond progression until the patient start the treatment per this protocol
• First-line cytotoxic chemotherapy received as palliative treatment is acceptable after the failure of Lazertinib (Patients with disease progression after adjuvant or neoadjuvant chemotherapy within 6 months are eligible to participate)
• Patient with MET amplification FISH GCN ≥5 and/or MET/CEP7 ≥ 2 (If additional resistance mechanism to lazertinib, such as C797S, is observed with MET amplification, the recruitment needs to be discussed in advance with the principal investigator)
• Available tissue for MET FISH
• Age of 19 or more
• Performance status of Eastern Cooperative Oncology Group 0 to 2
• Expected minimum life expectancy of 12 weeks
• Adequate organ function

• Absolute neutrophil count (ANC) ≥1500cells/mm3
• Platelet count ≥100,000cells/mm3
• Total bilirubin ≤1.5 x upper limit of normal(ULN)
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN (or ≤5.0 x ULN, if liver metastasis is present)
• Creatinine level ≤1.5 x upper limit of normal (ULN) or creatinine clearance ≥ 45mL/min (Calculated with Cockcroft- Gault equation)
• Available to provide the adequate tissue and blood for the genomic tests

• At least 20 unstained slide and 20 cc of blood at baseline and disease progression (If not, participant must be confirmed by the principal investigator
• Agreed to perform re-biopsy at the timepoint of disease progression
• Female subjects must either be of non-reproductive potential
• Subject willing and able to comply with the protocol
• Signed written informed consent

Exclusion criteria

• Previously treatment with any kind of EGFR TKI other than lazertinib
• All concurrent and/or other active malignant tumors requiring systemic therapy within 2 years prior to the initial administration of the investigational drug (However, the patient may participate if previous malignant tumor has been cured, and no further treatment is required)
• Uncontrolled central nervous system metastases
• Spinal cord compression, leptomeningeal carcinomatosis
• Uncontrolled systemic illness, including uncontrolled hypertension, active bleeding, or active infection
• Radiotherapy with a wide field of radiation within 2 weeks or radiotherapy with a limited field of radiation (localized radiotherapy or gamma knife surgery) for palliation within 1 week
• Any unresolved toxicities from prior therapy, greater than CTCAE grade 1
• Prior history of interstitial lung disease (ILD) or ILD like symptoms
• Mean QT interval corrected for heart rate (QTc) ≥ 470 ms
• No measurable lesion
• Unable to swallow the product due to refractory nausea, vomiting or chronic gastrointestinal disease