Clinical Trial of YH25448(Lazertinib) as the First-line Treatment in Patients With EGFR Mutation Positive Locally Advanced or Metastatic NSCLC (LASER301)
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| ClinicalTrials.gov Identifier: NCT04248829 |
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Recruitment Status :
Active, not recruiting
First Posted : January 30, 2020
Results First Posted : March 22, 2024
Last Update Posted : April 18, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Non-Small Cell Lung Cancer | Drug: Lazertinib 240 mg/160 mg Drug: Gefitinib 250 mg Drug: Lazertinib-matching placebo 240 mg/160 mg Drug: Gefitinib-matching placebo 250 mg | Phase 3 |
YH25448 is an oral, highly potent, mutant-selective and irreversible EGFR Tyrosine-kinase inhibitors (TKIs) that targets both the T790M mutation and activating EGFR mutations while sparing wild type EGFR.
This is a Phase III, Randomized, Double-blind study evaluating the efficacy and safety of YH25448 (240 mg orally, once daily) versus Gefitinib (250 mg orally, once daily) in patients with locally advanced or metastatic NSCLC that is known to be EGFR sensitizing mutation (EGFRm) positive, treatment-naïve and eligible for first-line treatment with an EGFR-TKI.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 393 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Approximately 380 patients will be randomized in a 1:1 ratio to either lazertinib (n=190) or gefitinib (n= 190). Following objective disease progression according to RECIST v1.1, as per investigator assessment, patients who were randomized to gefitinib arm may have the option to receive open-label lazertinib |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase III, Randomized, Double-blind Study to Assess the Efficacy and Safety of Lazertinib Versus Gefitinib as the First-line Treatment in Patients With Epidermal Growth Factor Receptor Sensitizing Mutation Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer |
| Actual Study Start Date : | February 13, 2020 |
| Actual Primary Completion Date : | July 29, 2022 |
| Estimated Study Completion Date : | June 2024 |
| Arm | Intervention/treatment |
|---|---|
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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
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Drug: Lazertinib 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
Other Name: YH25448 240 mg/160 mg Drug: Gefitinib-matching placebo 250 mg The initial dose for Gefitinib-matching placebo (250 mg once daily) cannot be reduced to a lower dose
Other Name: Iressa-matching placebo 250 mg |
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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
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Drug: Gefitinib 250 mg
The initial dose for Gefitinib (250 mg once daily) cannot be reduced to a lower dose
Other Name: Iressa 250 mg Drug: Lazertinib-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
Other Name: YH25448-matching placebo 240 mg/160 mg |
- Progression-Free Survival (PFS) According to RECIST v1.1 by Investigator Assessment [ 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. ]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).
- Objective Response Rate (ORR) According to RECIST v1.1 by Investigator Assessments [ 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. ]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.
- Duration of Response (DoR) According to RECIST v1.1 by Investigator Assessments [ 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. ]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.
- Disease Control Rate (DCR) According to RECIST v1.1 by Investigator Assessments [ 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. ]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.
- Depth of Response According to RECIST v1.1 by Investigator Assessments [ Time Frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression. ]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 to Response According to RECIST v1.1 by Investigator Assessments [ Time Frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression. ]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.
- Overall Survival (OS) [ 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.) ]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.
- Plasma Concentrations 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. ]To characterize the pharmacokinetics (PK) of lazertinib.
- Cerebrospinal Fluid (CSF) Concentrations of Lazertinib [ Time Frame: A cerebrospinal fluid (CSF) sample once collected from participants with brain metastases, at Cycle 5 Day 1 or afterward. ]To characterize the pharmacokinetics (PK) of lazertinib.
- Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 Items (QLQ-C30) [ 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). ]
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
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Lung Cancer 13 Items (EORTC QLQ-LC13) [ 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). ]
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.
- Change From Baseline in Euro-Quality of Life-5 Dimension-5 Level (EQ-5D-5L) [ 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). ]
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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Pathologically confirmed adenocarcinoma of the lung
- Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy
- At least 1 of the 2 common EGFR mutations known to be associated with EGFR TKI sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations
- Treatment-naïve for locally advanced or metastatic NSCLC
- WHO performance status score of 0 to 1 with no clinically significant deterioration over the previous 2 weeks before randomization
- At least 1 measurable lesion, not previously irradiated and not chosen for biopsy during the study Screening period
Exclusion Criteria:
- Symptomatic and unstable brain metastases
- Leptomeningeal metastases
- Symptomatic spinal cord compression
- History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
- Any medical conditions requiring chronic continuous oxygen therapy
- History of any malignancy other than the disease under study within 3 years before randomization
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Any cardiovascular disease as follows:
- History of symptomatic chronic heart failure or serious cardiac arrhythmia requiring active treatment
- History of myocardial infarction or unstable angina within 24 weeks of randomization
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04248829
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Documents provided by Yuhan Corporation:
| Responsible Party: | Yuhan Corporation |
| ClinicalTrials.gov Identifier: | NCT04248829 |
| Other Study ID Numbers: |
YH25448-301 |
| First Posted: | January 30, 2020 Key Record Dates |
| Results First Posted: | March 22, 2024 |
| Last Update Posted: | April 18, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | 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 Materials: |
Study Protocol Statistical Analysis Plan (SAP) |
| Time Frame: | Beginning 1 year and ending 5 years after all trial primary and secondary endpoints were assessed. |
| Access Criteria: | 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. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
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Locally Advanced EGFR Sensitizing Mutation Metastatic EGFR Sensitizing Mutation EGFR TKI Ex19del L858R First-line |
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