Neoadjuvant Lazertinib Therapy in EGFR-Mutation Positive Lung Adenocarcinoma Detected by BALF Liquid Biopsy

Study Overview
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Brief Summary
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Complete surgical resection is the standard treatment in early-stage lung cancer. However, the patients with early resected Epidermal Growth Factor Receptor(EGFR)-mutated lung cancers have high recurrence rate. The efficacy of neoadjuvant treatment by first-generation EGFR-Tyrosine Kinase Inhibitor(TKI) has been demonstrated, however, that of the third-generation EGFR-TKI(lazertinib) has not yet been fully investigated. The aim of this study is to evaluate the efficacy of neoadjuvant Lazertinib in resectable EGFR mutation-positive NSCLC and clinical application of extracellular vesicles(EVs) based BALF liquid biopsy to identify EGFR mutation without invasive tissue biopsy.

Detailed Description
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The neoadjuvant treatment of 3rd-generation EGFR-TKI, lazertinib for 9 weeks before surgery is administrated. After the surgery, the patients with the tumor over stage 2 are given the lazertinib to prevent recurrence for 3 years or until recurrence. In early lung cancer, a tissue biopsy is often difficult due to the small size or the risky location. We collect bronchoalveolar lavage fluid for liquid biopsy and lazertinib is administrated according to the result of BALF liquid EGFR genotyping.

Official Title
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A Phase II, Single-Center, Single-Arm, Prospective Study of Neoadjuvant Lazertinib Therapy in Resectable EGFR-Mutation Positive Lung Adenocarcinoma Patients Detected by Broncho-alveolar Lavage Fluid(BALF) Liquid Biopsy

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Neoadjuvant lazertinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 19 years Patients with suspected lung cancer on chest CT findings Patients with the following EGFR gene mutations in the test on bronchoalveolar lavage fluid: E19Del, L858R alone or concurrent rare EGFR gene mutations (T790M, G719X, exon 20 insertion, S768I) Patients whose tumor can be completely resected by surgery: patients with stage I-IIIB, or stage IVA who has single metastasis Patients not previously treated with EGFR-TKIs such as gefitinib, erlotinib, afatinib, dacomitinib Patients with the measurable lesion of 1 cm or more according to RECIST v1.1 Eastern Cooperative Oncology Group (ECOG) 0-1 EGFR-TKIs (gefitinib, erlotinib, afatinib,dacomitinib) naive patients Patients with adequate pulmonary and heart function for surgery Adequate organ function defined as Hemoglobin ≥ 9.0g/dL Absolute neutrophil count ≥ 1500/mm3 Platelet ≥ 100,000 /mm3 Serum creatinine≤ normal range*1.5x Aminotransferase/Alkaline phosphatase ≤normal range*2.5x Total bilirubin ≤1.5 mg/dL Liver metastasis: Aminotransferase/Alkaline phosphatase ≤ normal range* 5x Bone metastasis Alkaline phosphatase ≤ normal range* 5x Female patients with childbearing potential should be using adequate contraceptive measures. Female patients must have evidence of non-child-bearing potential(Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments) Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception for at least 14 days prior to administration of the first dose of study treatment, during the study, and for 3 months following the last dose of Lazertinib. Exclusion Criteria: Uncontrolled active interstitial lung disease Pathologically confirmed N3 disease Uncontrolled stage III-IV other malignancy Uncontrolled Hypertension, Congestive Heart failure with New York Heart Association(NYHA) ≥ 3, acute myocardial infarct history within 6 months before screening. 2nd- 3rd Atrio-Ventricular(AV) block or complete AV block Gastrointestinal diseases (e.g. Chron's disease, ulcerative colitis) or malabsorption syndrome that would impact on drug absorption Active infection requiring ongoing treatment(e.g. active Hepatitis B virus, Hepatitis C virus or Human immunodeficiency virus) History of hypersensitivity to active or inactive excipients of Lazertinib or drugs with a similar chemical structure. No ability to comply with protocol requirements.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant Lazertinib<br>Lazertinib as neoadjuvant treatment is administrated for 9 weeks before surgery. After surgical intervention the treatment is administrated upto 3 years to the patients with over stage 2 tumor. Treatment is discontinued in case of unacceptable toxicity or disease progression. | Drug: Neoadjuvant lazertinib<br>* Lazertinib 240mg p.o once daily.<br>* Other names: Neoadjuvant LECLAZA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | The objective response rate (ORR) evaluated with RECIST version 1.1. It is defined as the proportion of patients with complete response (CR) or partial response (PR) after 9 weeks of lazertinib administration | 9 weeks after the starting day of the lazertinib | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Down-staging rate | The rate of downstage by pathology stage compared with clinical stage | From the day of screening to an average of 16 weeks after the first dose | 
| Major pathological response | The proportion of patients with less than 10% of the cancer cells in the surgical sample. | From the day of screening to an average of 16 weeks after the first dose | 
| Disease-free survival rate | The length of time after surgical resection the patient remains free of recurrence/progression or death, whatever the cause. | up to 3 years after surgery | 
| The concordance rate of EGFR mutations between surgical tissue and BAL fluid samples | The concordance rate of BALF EGFR mutation compared with EGFR mutation status of surgical resected tissue | From the day of screening day to an average of 16 weeks after the first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EGFR mutation, extracellular vesicle, bronchoalveolar lavage, liquid biopsy, lazertinib