Clinical Trial of YH25448(Lazertinib) as the First-line Treatment in Patients With EGFR Mutation Positive Locally Advanced or Metastatic NSCLC (LASER301)

Browse trials for

• Carcinoma, Non-Small-Cell Lung 6,488
• Adenocarcinoma of Lung 303

Keywords

• Locally Advanced EGFR Sensitizing Mutation
• Metastatic EGFR Sensitizing Mutation
• EGFR TKI
• Ex19del
• L858R
• First-line
• YH25448
• Advanced Non-Small Cell Lung Cancer
• Adenocarcinoma of lung
• Non-squamous carcinoma of lung
• Phase III
• Lazertinib

Carcinoma, Non-Small-Cell Lung

6,488 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,632 are open to participants now.

This study's enrollment of 393 is above the median of 62 across 5,213 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.

Lead sponsor

Yuhan Corporation is the lead sponsor of 107 studies on the registry; 6 are open to participants now.

Study arms

• Experimental
  Lazertinib + Gefitinib-matching placebo

  Lazertinib (240 mg or 160 mg orally, once daily) plus Gefitinib-matching placebo (250 mg orally, once daily) in accordance with the randomization schedule

  Drug: Lazertinib 240 mg/160 mg · Drug: Gefitinib-matching placebo 250 mg

• Active comparator
  Gefitinib + Lazertinib-matching placebo

  Gefitinib (250 mg orally, once daily) plus Lazertinib-matching placebo (240 mg or 160 mg orally, once daily) in accordance with the randomization schedule

  Drug: Gefitinib 250 mg · Drug: Lazertinib-matching placebo 240 mg/160 mg

Interventions

• DrugLazertinib 240 mg/160 mg

  The initial dose of lazertinib 240 mg (3 tablets of 80 mg lazertinib) once daily can be reduced to 160 mg once daily (2 tablets of 80 mg lazertinib) under specific circumstances

  Also known as: YH25448 240 mg/160 mg

• DrugGefitinib 250 mg

  The initial dose for Gefitinib (250 mg once daily) cannot be reduced to a lower dose

  Also known as: Iressa 250 mg

• DrugLazertinib-matching placebo 240 mg/160 mg

  The initial dose of lazertinib-matching placebo 240 mg (3 tablets of 80 mg lazertinib-matching placebo) once daily can be reduced to 160 mg once daily (2 tablets of 80 mg lazertinib-matching placebo) under specific circumstances

  Also known as: YH25448-matching placebo 240 mg/160 mg

• DrugGefitinib-matching placebo 250 mg

  The initial dose for Gefitinib-matching placebo (250 mg once daily) cannot be reduced to a lower dose

  Also known as: Iressa-matching placebo 250 mg

Primary outcomes

1. Progression-Free Survival (PFS) According to RECIST v1.1 by Investigator Assessment

   PFS was defined as the time from randomization until the date of objective progression or death(by any cause whichever comes first based on investigator assessment using RECIST v1.1 and was used to assess the efficacy of lazertinib compared to the gefitinib).

   Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression, assessed up to 29 months per participant.

Secondary outcomes

1. Objective Response Rate (ORR) According to RECIST v1.1 by Investigator Assessments

   ORR was defined as the percentage of participants with measurable disease with at least on visit response of complete response(CR) or Partial response(PR) and it was used to further assess the efficacy of lazertinib compared with gefitinib.

   Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression, assessed up to 29 months per participant.

2. Duration of Response (DoR) According to RECIST v1.1 by Investigator Assessments

   DoR was defined as the time from the date of first documented response(CR or PR) until the date of documented progression or death, whichever comes first and was used to further assess the efficacy of lazertinib compared with gefitinib.

   Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression, assessed up to 29 months per participant.

3. Disease Control Rate (DCR) According to RECIST v1.1 by Investigator Assessments

   DCR was defined as the percentage of participants who have a best overall response of CR or PR or SD(SD at \>= 6weeks prior to any PD event) and was used to further assess the efficacy of lazertinib compared with gefitinib.

   Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression, assessed up to 29 months per participant.

4. Depth of Response According to RECIST v1.1 by Investigator Assessments

   The depth of response was defined as the best percent change in the sum of diameters of target lesions in the absense of new lesions or progression of non-target lesions compared to the baseline and was used to further assess the efficacy of lazertinib compared with gefitinib.

   Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression.

5. Time to Response According to RECIST v1.1 by Investigator Assessments

   Time to Response was defined as the time from the date of randomization until the date of first documented response and was used to further assess the efficacy of lazertinib compared with gefitinib.

   Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression.

6. Overall Survival (OS)

   OS was defined as the time from the date of randomization until the date of death due to any cause and was used to further assess the efficacy of lazertinib compared with gefitinib.

   Time frame: From the randomization to end of study or date of death from any cause, whichever comes first, assessed every 6 weeks. (Up to 29 months per participant.)

7. Plasma Concentrations of Lazertinib

   To characterize the pharmacokinetics (PK) of lazertinib.

   Time frame: Blood samples collected from each participant at pre-dose, 1 to 3 hours, and 4 to 6 hours post-dose on Day 1 Cycle 1, Day 1 Cycle 2, Day 1 Cycle 5, Day 1 Cycle 9, and Day 1 Cycle 13.

8. Cerebrospinal Fluid (CSF) Concentrations of Lazertinib

   To characterize the pharmacokinetics (PK) of lazertinib.

   Time frame: A cerebrospinal fluid (CSF) sample once collected from participants with brain metastases, at Cycle 5 Day 1 or afterward.

9. Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 Items (QLQ-C30)

   The EORTC QLQ-C30 consists of 30 items and measures cancer participants' functioning (health related quality of life (HRQoL)) and symptoms for all cancer types. Questions can be grouped into 5 multi item functional scales (physical, role, emotional, cognitive, and social); 3 multi item symptom scales (fatigue, pain, nausea/vomiting); a 2 item global HRQoL scale; 5 single items assessing additional symptoms commonly reported by cancer participants (dyspnea, loss of appetite, insomnia, constipation, diarrhea) and 1 item on the financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. * a high score for a functional scale represents a high / healthy level of functioning * a high score for the global health status / QoL represents a high QoL * but a high score for a symptom scale / item represents a high level of symptomatology / problems

   Time frame: Questionnaires completed at Cycle 1 Day1 , Cycle2 Day 1 and then every 6 weeks relative to the randomization date until 28d safety f/u or progression f/u visit(whichever is later).

10. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Lung Cancer 13 Items (EORTC QLQ-LC13)

    The EORTC QLQ-LC13 includes questions assessing cough, hemoptysis, dyspnea, site specific pain (symptoms), sore mouth, dysphagia, peripheral neuropathy, and alopecia (treatment related side effects), and pain medication. The items on both measures were scaled and scored using the recommended EORTC procedures. Raw scores were transformed to a linear scale ranging from 0 to 100, with a higher score representing a higher level of functioning or higher level of symptoms. Provided at least half of the items in the scale were completed, the scale score was calculated using only those items for which values existed.

    Time frame: Questionnaires completed at Cycle 1 Day1 , Cycle2 Day 1 and then every 6 weeks relative to the randomization date until 28d safety f/u or progression f/u visit(whichever is later).

11. Change From Baseline in Euro-Quality of Life-5 Dimension-5 Level (EQ-5D-5L)

    The EQ-5D comprises the following two questionnaires: * The EQ-5D comprises 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension comprises five levels (no problems, slight problems, moderate problem, severe problem, unable/extreme problems). * The EQ VAS records the participants self-rated health status on a vertical graduated (0-100) visual analogue scale. The patient's self-rated health is assessed on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) by the EQ-VAS.

    Time frame: Questionnaires completed at Cycle 1 Day1 , Cycle2 Day 1 and then every 6 weeks relative to the randomization date until 28d safety f/u or progression f/u visit(whichever is later).

Baseline characteristics

Publications

• Soo RA, Cho BC, Kim JH, Ahn MJ, Lee KH, Zimina A, Orlov S, Bondarenko I, Lee YG, Lim YN, Lee SS, Lee KH, Pang YK, Fong CH, Kang JH, Lim CS, Danchaivijitr P, Kilickap S, Yang JC, Arslan C, Lee H, Park SN, Cicin I. Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset Analysis. J Thorac Oncol. 2023 Dec;18(12):1756-1766. doi: 10.1016/j.jtho.2023.08.017. Epub 2023 Oct 22. PubMed 37865896 ↗
• Cho BC, Ahn MJ, Kang JH, Soo RA, Reungwetwattana T, Yang JC, Cicin I, Kim DW, Wu YL, Lu S, Lee KH, Pang YK, Zimina A, Fong CH, Poddubskaya E, Sezer A, How SH, Danchaivijitr P, Kim Y, Lim Y, An T, Lee H, Byun HM, Zaric B. Lazertinib Versus Gefitinib as First-Line Treatment in Patients With EGFR-Mutated Advanced Non-Small-Cell Lung Cancer: Results From LASER301. J Clin Oncol. 2023 Sep 10;41(26):4208-4217. doi: 10.1200/JCO.23.00515. Epub 2023 Jun 28. PubMed 37379502 ↗

Study documents

• Study protocol · Sep 3, 2020
• Statistical analysis plan · Sep 16, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — De-identified individual participant data (including data dictionaries) that underline the results reported in study-related publications will be made available during the period beginning 1 year and ending 5 years after all trial primary and secondary endpoints were assessed. Only requests from researchers who provide a methodologically sound proposal will be reviewed and approved by the sponsor. The analysis type should be in accordance with aims in the proposal approved by the sponsor. Proposals should be directed to hmbyun@yuhan.co.kr. Other documents(i.e. a summary of the study results, study protocol, statistical analysis plan) will be posted in the publicly accessible database (i.e. clinicaltrials.gov) no later than 1 year after the study's primary completion date.

Supporting information: Study protocol, Sap