Impact of Lazertinib Dose Modification on Effectiveness and Safety

Impact of Lazertinib Dose Modification on Effectiveness and Safety in EGFR T790M-Positive Advanced Lung Cancer

The primary objective is to evaluate Progression Free Survival (PFS) of the group (160 mg group) in which dose reduction was performed for 12 weeks after the first administration of Lazertinib.

The Secondary objectives of this study are as follows.

1. To evaluate Progression-free survival (PFS) of the group maintaining the same dose (240mg group) and the group in which dose reduction was performed (160mg group) for 12 weeks after the first administration of Lazertinib
2. In the group maintaining the same dose (240mg group) and the group in which dose reduction was performed (160mg group) for 12 weeks after the first administration of Lazertinib, Time-to-Treatment Discontinuation(TTD), Objective Response Rate(ORR), Disease Control Rate(DCR), Tumor shrinkage and Overall Survival(OS) is evaluated.
3. In the group maintaining the same dose (240mg group) and the group in which dose reduction was performed (160mg group) for 12 weeks after the first administration of Lazertinib, specific reasons (adverse event name, grade, etc.) according to Lazertinib dose adjustment is evaluated.
4. To evaluate the treatment profile of Lazertinib including duration of treatment, dose adjustment, and reason for discontinuation of treatment.
5. To evaluate the safety of Lazertinib in the 240 mg and 160 mg groups

Study Overview

• Status: Not yet recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Lazertinib

Detailed Description

This study is a prospective multi-center observational study, and 11 institutions will participate to enroll 200 subjects competitively. We will evaluate the efficacy and safety of Lazertinib according to maintenance of the 240mg dose and reduction of the 160mg dose for 12 weeks after the first administration of Lazertinib in non-small cell lung cancer patients confirmed to be T790M mutation-positive after treatment failure with first- or second-generation EGFR-TKIs. The study period is up to 3 years from the date of IRB approval. Follow-up is 2 years from the last subject enrollment, and data will be collected through periodic medical record review during Lazertinib administration for enrolled subjects.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Min Ki Lee, MD, PhD; Phone Number: +82-51-240-7216; Email: leemk@pusan.ac.kr
• Study Contact Backup: Name: Jung Seop Eom, MD, PhD; Phone Number: +82-51-240-7889; Email: ejspulm@gmail.com

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital
    • Contact: Min Ki Lee, MD, PhD; Phone Number: +82-51-240-7216; Email: leemk@pusan.ac.kr
    • Contact: Jung Seop Eom, MD, PhD; Phone Number: +82-51-240-7889; Email: ejspulm@gmail.com
  • Busan, Korea, Republic of, 48108
    • Inje University Haeundae Paik Hospital
    • Contact: Jin-han Park, MD, PhD; Phone Number: +82-51-240-2211; Email: h00389@paik.ac.kr
  • Busan, Korea, Republic of, 49201
    • Dong-A University Hospital
    • Contact: Insu Kim, MD, PhD; Phone Number: +82-51-240-5597; Email: wisedoc08@gmail.com
  • Busan, Korea, Republic of, 47392
    • Inje University Busan Paik Hospital
    • Contact: Hyun-kyung Lee, MD, PhD; Phone Number: +82-51-890-6243; Email: goodoc@gmail.com
  • Busan, Korea, Republic of, 49267
    • Kosin University Gospel Hospital
    • Contact: Tae Won Jang, MD, PhD; Phone Number: +82-51-990-6637; Email: jangtw22@hanmail.net
  • Daegu, Korea, Republic of, 41404
    • Kyungpook National University Chilgok Hospital
    • Contact: Sun Ha Choi, MD, PhD; Phone Number: +82-53-200-3091; Email: sunha20@gmail.com
  • Daegu, Korea, Republic of, 42415
    • Yeungnam University Medical Center
    • Contact: June Hong Ahn, MD, PhD; Phone Number: +82-53-640-6577; Email: fireajh@gmail.com
  • Daegu, Korea, Republic of, 41944
    • Kyungpook National University Hospital
    • Contact: Ji Eun Park, MD, PhD; Phone Number: +82-53-200-5505; Email: jieun@knu.ac.kr
  • Daegu, Korea, Republic of, 42472
    • Daegu Catholic University Medical Center
    • Contact: Chi-Young Jung, MD, PhD; Phone Number: +82-53-650-3263; Email: jcy2475@cu.ac.kr
  • Daegu, Korea, Republic of, 42601
    • Keimyung University Dongsan Medical Center
    • Contact: Sun Hyo Park, MD, PhD; Phone Number: +82-53-258-7737; Email: ibagu70@hanmail.net
  • Yangsan, Korea, Republic of, 50612
    • Pusan National University Yangsan Hospital
    • Contact: Seong Hoon Yoon, MD, PhD; Phone Number: +82-55-360-1415; Email: drysh79@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients who agreed to participate in this study among patients scheduled to receive Lazertinib after T790M mutation was confirmed positive after treatment with 1st or 2nd generation EGFR-TKIs

Description

Inclusion Criteria:

1. Patients who agreed in writing to participate in this study
2. Adult men and women over 20 years of age
3. Patients with locally advanced or metastatic, recurrent non-small cell lung cancer with EGFR mutation (based on AJCC 8th edition)
4. Patients with confirmed disease progression after 1st or 2nd generation EGFR-TKI treatment
5. Patients scheduled to receive Lazertinib after T790M mutation was confirmed positive in tissue or plasma

Exclusion Criteria:

1. Patients who are receiving or have already completed Lazertinib
2. Patients whose life expectancy is less than 12 weeks

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
240mg group; Maintenance of the 240mg dose for 12 weeks after the first administration of Lazertinib	Drug: Lazertinib; Lazertinib 240mg(3tablets, 80mg/1tablet), once a day(QD), oral(PO), until disease progression or unacceptable toxicity; Other Names: LECLAZA
160mg group; Reduction of the 160mg dose for 12 weeks after the first administration of Lazertinib	Drug: Lazertinib; Lazertinib 240mg(3tablets, 80mg/1tablet), once a day(QD), oral(PO), until disease progression or unacceptable toxicity; Other Names: LECLAZA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival(PFS)	Progression-free survival is defined as the period from the start of Lazertinib administration to the time when objective disease progression is confirmed or death from any cause during treatment, whichever occurs first.	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-Treatment Discontinuation (TTD)	Time-to-Treatment Discontinuation (TTD) is defined as the time from the start of Lazertinib administration to the point at which Lazertinib administration was discontinued for any reason.	Up to approximately 3 years
Objective Response Rate(ORR)	Objective Response Rate (ORR) is defined as the proportion of subjects whose best overall response was complete response(CR) or partial response(PR) during the period of Lazertinib administration.	Up to approximately 3 years
Disease Control Rate (DCR)	Disease Control Rate (DCR) is defined as the proportion of subjects whose best overall response was complete response(CR), partial response(PR), or stable disease(SD) during the period of Lazertinib administration.	Up to approximately 3 years
Tumor shrinkage	Tumor shrinkage is defined as the ratio of the size of the primary lesion at the time of baseline before the first administration of Lazertinib and the size of the primary lesion at the time of maximum overall response during Lazertinib administration.	Up to approximately 3 years
Overall Survival (OS)	Overall Survival (OS) is defined as the period from the start of Lazertinib administration to death from any cause.	Up to approximately 3 years

Collaborators and Investigators

• Sponsor: Pusan National University Hospital
• Collaborators: Yuhan Corporation
• Investigators: Principal Investigator: Min Ki Lee, MD, PhD, Pusan National University Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): February 1, 2023
• Primary Completion (ANTICIPATED): December 31, 2025
• Study Completion (ANTICIPATED): December 31, 2025

Study Registration Dates

• First Submitted: January 29, 2023
• First Submitted That Met QC Criteria: January 29, 2023
• First Posted (ACTUAL): February 8, 2023

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: January 29, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; EGFR-TKI; Lazertinib
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Lazertinib
• Other Study ID Numbers: PNU-001; LASER IIT-018 (OTHER_GRANT: Yuhan Corporation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No