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

July 20, 2022 updated by: Kye Young Lee, Konkuk University Medical Center

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 05030
        • Recruiting
        • Konkuk University Medical Center
        • Contact:
          • In Ae Kim, M.D. Ph.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Neoadjuvant Lazertinib
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
Lazertinib 240mg p.o once daily.
Other Names:
  • Neoadjuvant LECLAZA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate
Time Frame: 9 weeks after the starting day of the lazertinib
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
Time Frame: From the day of screening to an average of 16 weeks after the first dose
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
Time Frame: From the day of screening to an average of 16 weeks after the first dose
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
Time Frame: up to 3 years after surgery
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
Time Frame: From the day of screening day to an average of 16 weeks after the first dose
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Konkuk University Medical Center

Collaborators

Yuhan Corporation

Investigators

  • Principal Investigator: Kye Young Lee, Konkuk University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 19, 2022

Primary Completion (Anticipated)

May 19, 2024

Study Completion (Anticipated)

May 19, 2027

Study Registration Dates

First Submitted

July 15, 2022

First Submitted That Met QC Criteria

July 20, 2022

First Posted (Actual)

July 21, 2022

Study Record Updates

Last Update Posted (Actual)

July 21, 2022

Last Update Submitted That Met QC Criteria

July 20, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NeolazBAL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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