Lazertinib for NSCLC Harboring Activating EGFR Mutations in TKI naïve Patients

Study Overview
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Brief Summary
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The primary objective is to evaluate the efficacy/safety of lazertinib and to explore the resistance mechanism of lazertinib as first-line in patients with NSCLC harboring activating EGFR mutations.

Detailed Description
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As the 3rd generation EGFR TKI become a standard treatment option for the 1st line therapy in EGFR mutated patients, necessity for evaluating resistant mechanism to determine the matched subsequent therapeutic option has been highlighted. The idea of understanding the exact resistance mechanism to 1st line 3rd generation EGFR TKI treatment is emphasized based on the observation that resistance mechanism is different based on osimertinib used as 1st line or 2nd line treatment.6,7 Although resistance mechanisms to lazertinib in patients with prior EGFR TKI treatment have been studied, there are no current data available regarding the resistance mechanism after first-line lazertinib treatment. Based on this observation, PI designed this study to elucidate the efficacy/safety of Lazertinib and to explore resistance mechanisms of 1st line lazertinib treatment in NSCLC patients with activating EGFR mutation.

Official Title
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Lazertinib for NSCLC Harboring Activating EGFR Mutations in TKI naïve Patients: A Single-arm, Phase II Single-center Trial

Conditions
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NSCLC

Intervention / Treatment
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* Drug: Lazertinib group


Participation Criteria
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Eligibility Criteria
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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). Patients who underwent curative intent surgery or definitive CRT and experience recurrence after 6 months are eligible. Stage IIIC or IV by AJCC 8th edition Confirmed EGFR mutations (exon 19 deletion, L858R)(The result from both cell-free DNA or tissue-based DNA from the local test is allowed.) 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. Available to provide the adequate tissue and blood for the genomic tests- At least 15 unstained slide and 20 cc of blood at baseline (mandatory) and disease progression. Agreed to perform re-biopsy at the timepoint of disease progression. At least two weeks after the chemotherapy 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 (Previously chemotherapy treated patients is allowed) Any concurrent and/or other active malignancy that has required systemic treatment within 2 years of first dose of study drug. (allowed for participation if investigator decided that previous malignancy is cured and not need for any additional treatment) Uncontrolled central nervous system metastases- patient with asymptomatic brain metastases or CNS symptom manageable with TKI and evaluated by investigator can be enrolled. 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 Mean QT interval corrected for heart rate (QTc) ≥ 470 ms No measurable lesion Unable to swallow the product due to refractory nausea, vomiting or chornic gastrointestinal disease.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: A single-arm, phase II single-center trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lazertinib group<br>Lazertinib 240mg daily (1 cycle of 21 days) | Drug: Lazertinib group<br>* Lazertinib 240mg, Once, po, daily (1 cycle of 21 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival | C1D1 until the date of objective disease progression or death | through study completion, an average of 18.0 month | 
| Resistance mechanism analysis | The mutation profile of baseline and at the timepoint of resistance will be evaluated using tissue and cfDNA | Screening, Discontiunuation Visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | as the percentage of patients with measurable disease with at least one visit response of complete response (CR) or partial response (PR) | through study completion, an average of 18.0 month | 
| Duration of Response (DoR) | as the time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first | through study completion, an average of 18.0 month | 
| Disease control rate (DCR) | as the percentage of patients who have a best overall response of CR or PR or stable disease (SD at ≥ 6 weeks, prior to any PD event) | through study completion, an average of 18.0 month | 
| Overall survival (OS) | s the time from the date of C1D1 until the date of death due to any cause | through study completion, an average of 18.0 month | 
| intracranial PFS (iPFS) | as the time from C1D1 until the date of objective intracranial disease progression or death whichever comes first in patients for the iFAS | through study completion, an average of 18.0 month | 
| intracranial ORR (iORR) | as the percentage of patients who have at least 1 CR or PR in intracranial lesion, according to RECIST v1.1 prior to disease progression in patients who have at least one measurable intracranial lesion at baseline | through study completion, an average of 18.0 month | 
| intracranial DCR (iDCR) | as the percentage of patients who have a best intracranial overall response of CR or PR or SD in patients who have at least one measurable intracranial lesion at baseline | through study completion, an average of 18.0 month |