Neoadjuvant treatment with lazertinib for lung cancer patients with specific mutations

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

This study is testing if a new lung cancer treatment called lazertinib can help patients with specific mutations feel better and reduce the chances of their cancer coming back after surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 19 Years and up
• Sex: All
• Sponsor: Konkuk University Medical Center (Academic / other)
• Drugs / interventions: gefitinib, erlotinib, afatinib, dacomitinib, Lazertinib
• Locations: 1 site (Seoul)
• Trial ID: NCT05469022 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of neoadjuvant lazertinib therapy in patients with resectable non-small cell lung cancer (NSCLC) that have specific EGFR mutations. Patients will receive lazertinib for 9 weeks prior to surgery, followed by additional treatment for those with advanced disease to prevent recurrence. The study also utilizes bronchoalveolar lavage fluid for liquid biopsy to identify EGFR mutations, minimizing the need for invasive tissue biopsies. The goal is to improve outcomes for patients with early-stage lung cancer who are at high risk of recurrence.

Who should consider this trial

Good fit: Ideal candidates include adults aged 19 and older with resectable EGFR mutation-positive NSCLC and no prior treatment with EGFR-TKIs.

Not a fit: Patients with non-resectable tumors or those who have previously received EGFR-TKI treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce recurrence rates in patients with EGFR-mutated lung cancer.

How similar studies have performed: While the efficacy of first-generation EGFR-TKIs has been established, the use of third-generation EGFR-TKIs like lazertinib in this context is novel and has not been fully tested in prior studies.

Eligibility criteria

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.

Where this trial is running

Seoul

• Konkuk University Medical Center — Seoul, South Korea (Recruiting)

Study contacts

• Principal investigator: Kye Young Lee — Konkuk University Medical Center
• Study coordinator: In Ae Kim, MD. PhD.

Conditions Non Small Cell Lung Cancer; EGFR mutation; extracellular vesicle; bronchoalveolar lavage; liquid biopsy; lazertinib