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

Primary Purpose

Non Small Cell Lung Cancer

Status

Recruiting

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Neoadjuvant lazertinib

About this trial

This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring EGFR mutation, extracellular vesicle, bronchoalveolar lavage, liquid biopsy, lazertinib

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Konkuk University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neoadjuvant Lazertinib

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Down-staging rate

The rate of downstage by pathology stage compared with clinical stage

Major pathological response

The proportion of patients with less than 10% of the cancer cells in the surgical sample.

Disease-free survival rate

The length of time after surgical resection the patient remains free of recurrence/progression or death, whatever the cause.

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

Full Information

NCT ID

NCT05469022

First Posted

July 15, 2022

Last Updated

July 20, 2022

Sponsor

Konkuk University Medical Center

Collaborators

Yuhan Corporation

1. Study Identification

Unique Protocol Identification Number

NCT05469022

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Recruiting

Study Start Date

May 19, 2022 (Actual)

Primary Completion Date

May 19, 2024 (Anticipated)

Study Completion Date

May 19, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Konkuk University Medical Center

Collaborators

Yuhan Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non Small Cell Lung Cancer

Keywords

EGFR mutation, extracellular vesicle, bronchoalveolar lavage, liquid biopsy, lazertinib

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Neoadjuvant Lazertinib

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Neoadjuvant lazertinib

Other Intervention Name(s)

Neoadjuvant LECLAZA

Intervention Description

Lazertinib 240mg p.o once daily.

Primary Outcome Measure Information:

Title

Objective response rate

Description

Time Frame

9 weeks after the starting day of the lazertinib

Secondary Outcome Measure Information:

Title

Down-staging rate

Description

The rate of downstage by pathology stage compared with clinical stage

Time Frame

From the day of screening to an average of 16 weeks after the first dose

Title

Major pathological response

Description

The proportion of patients with less than 10% of the cancer cells in the surgical sample.

Time Frame

From the day of screening to an average of 16 weeks after the first dose

Title

Disease-free survival rate

Description

The length of time after surgical resection the patient remains free of recurrence/progression or death, whatever the cause.

Time Frame

up to 3 years after surgery

Title

The concordance rate of EGFR mutations between surgical tissue and BAL fluid samples

Description

The concordance rate of BALF EGFR mutation compared with EGFR mutation status of surgical resected tissue

Time Frame

From the day of screening day to an average of 16 weeks after the first dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

In Ae Kim, MD. PhD.

Phone

+821035438353

20180618@kuh.ac.kr

First Name & Middle Initial & Last Name or Official Title & Degree

Kye Young Lee, MD,PhD.

Phone

821088963916

kyleemd@kuh.ac.kr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kye Young Lee

Organizational Affiliation

Konkuk University Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Konkuk University Medical Center

City

Seoul

ZIP/Postal Code

05030

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

In Ae Kim, M.D. Ph.D.

12. IPD Sharing Statement

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

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