None listed
Conditions
Interventions
Drug : Patients will be treated with Lazertinib + tepotinib based on the MET FISH results.
Lazertinib 240mg daily Tepotinib 500mg daily
Sponsors
Samsung Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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) 2. 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 3. 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) 4. 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) or if there is no MET FISH amplification, but MET IHC 3+ or higher patient. 5. Available tissue for MET FISH & MET IHC 6. Age of 19 or more 7. Performance status of Eastern Cooperative Oncology Group 0 to 2 8. Expected minimum life expectancy of 12 weeks 9. Adequate organ function a. Absolute neutrophil count (ANC) =1500cells/mm3 b. Platelet count =100,000cells/mm3 c. Total bilirubin =1.5 x upper limit of normal(ULN) d. Aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 x ULN (or =5.0 x ULN, if liver metastasis is present) e. Creatinine level =1.5 x upper limit of normal (ULN) or creatinine clearance = 45mL/min (Calculated with Cockcroft- Gault equation) 10. 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 11. Agreed to perform re-biopsy at the timepoint of disease progression 12. Female subjects must either be of non-reproductive potential 13. Subject willing and able to comply with the protocol 14. Signed written informed consent
Exclusion criteria
Exclusion criteria: 1) Previously treatment with any kind of EGFR TKI other than lazertinib 2) 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) 3) Uncontrolled central nervous system metastases 4) Spinal cord compression, leptomeningeal carcinomatosis 5) Uncontrolled systemic illness, including uncontrolled hypertension, active bleeding, or active infection 6) 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 7) Any unresolved toxicities from prior therapy, greater than CTCAE grade 1 8) Prior history of interstitial lung disease (ILD) or ILD like symptoms 9) Mean QT interval corrected for heart rate (QTc) = 470 ms 10) No measurable lesion 11) Unable to swallow the product due to refractory nausea, vomiting or chronic gastrointestinal disease 12) Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to randomization, unstable arrhythmias, or unstable angina Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate. 13) Pregnant or breastfeeding women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| objective response rate (ORR) | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival (PFS);Duration of Response (DoR);Disease control rate (DCR);Overall survival (OS) | — |
Countries
Korea, Republic of
Contacts
Public ContactSe-Hoon Lee
Samsung Medical Center
Outcome results
None listed