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

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

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.

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.

Inclusion Criteria:

1. Age ≥ 19 years
2. Patients with suspected lung cancer on chest CT findings
3. 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)
4. Patients whose tumor can be completely resected by surgery: patients with stage I-IIIB, or stage IVA who has single metastasis
5. Patients not previously treated with EGFR-TKIs such as gefitinib, erlotinib, afatinib, dacomitinib
6. Patients with the measurable lesion of 1 cm or more according to RECIST v1.1
7. Eastern Cooperative Oncology Group (ECOG) 0-1
8. EGFR-TKIs (gefitinib, erlotinib, afatinib,dacomitinib) naive patients
9. Patients with adequate pulmonary and heart function for surgery
10. 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
11. 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)
12. 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:

1. Uncontrolled active interstitial lung disease
2. Pathologically confirmed N3 disease
3. Uncontrolled stage III-IV other malignancy
4. 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
5. Gastrointestinal diseases (e.g. Chron's disease, ulcerative colitis) or malabsorption syndrome that would impact on drug absorption
6. Active infection requiring ongoing treatment(e.g. active Hepatitis B virus, Hepatitis C virus or Human immunodeficiency virus)
7. History of hypersensitivity to active or inactive excipients of Lazertinib or drugs with a similar chemical structure.
8. No ability to comply with protocol requirements.