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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04248829
Recruitment Status : Recruiting
First Posted : January 30, 2020
Last Update Posted : October 9, 2020
Sponsor:
Information provided by (Responsible Party):
Yuhan Corporation

Brief Summary:
This Phase III study will be conducted to evaluate the efficacy and safety of YH25448 as first-line treatment in locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) patients with EGFR mutations

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

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 380 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
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Gefitinib

Arm Intervention/treatment
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
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

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
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




Primary Outcome Measures :
  1. Progression-Free Survival (PFS) according to RECIST v1.1 by Investigator assessment [ Time Frame: The primary analysis of PFS based on investigator assessment will occur when PFS maturity is observed at approximately 27 months after the first patient is randomized ]
    To assess the efficacy of lazertinib compared with gefitinib as measured by PFS


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) according to RECIST v1.1 by Investigator assessments [ Time Frame: ORR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized ]
    To further assess the efficacy of lazertinib compared with gefitinib

  2. Duration of Response (DoR) according to RECIST v1.1 by Investigator assessments [ Time Frame: DoR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized ]
    To further assess the efficacy of lazertinib compared with gefitinib

  3. Disease Control Rate (DCR) according to RECIST v1.1 by Investigator assessments [ Time Frame: DCR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized ]
    To further assess the efficacy of lazertinib compared with gefitinib

  4. Depth of Response according to RECIST v1.1 by Investigator assessments [ Time Frame: Depth of Response analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized ]
    To further assess the efficacy of lazertinib compared with gefitinib

  5. Time to Response according to RECIST v1.1 by Investigator assessments [ Time Frame: Time to Response analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized ]
    To further assess the efficacy of lazertinib compared with gefitinib

  6. Overall survival (OS) [ Time Frame: OS will be analyzed at 2 time points: when PFS maturity is observed at approximately 27 months after the first patient is randomized, and when OS maturity is observed at approximately 45 months after the first patient is randomized ]
    To assess OS of lazertinib compared with gefitinib

  7. Plasma concentrations of lazertinib [ Time Frame: Plasma concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized ]
    To characterize the pharmacokinetics (PK) of lazertinib

  8. Plasma concentrations of Metabolite YH26334 [ Time Frame: Plasma concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized ]
    To characterize the PK of lazertinib metabolite YH26334

  9. Ratio of YH26334 to lazertinib plasma concentration [ Time Frame: Ratio of YH26334 to lazertinib plasma concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized ]
    To characterize the PK of lazertinib and YH26334

  10. Cerebrospinal fluid (CSF) concentrations of lazertinib [ Time Frame: CSF concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized ]
    To characterize the PK of lazertinib

  11. CSF concentrations of Metabolite YH26334 [ Time Frame: CSF concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized ]
    To characterize the PK of lazertinib metabolite YH26334

  12. Ratio of CSF to plasma concentration of lazertinib and YH26334 [ Time Frame: Ratio of CSF to plasma concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized ]
    To characterize the PK of lazertinib and YH26334

  13. Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 items (QLQ-C30) [ Time Frame: EORTC-QLQ-C30 analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized ]

    The EORTC QLQ-C30 consists of 30 items and measures cancer patients' 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 patients (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

  14. 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: EORTC QLQ-LC13 analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized ]

    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.


  15. Change From Baseline in Euro-Quality of Life-5 Dimension-5 level (EQ-5D-5L) [ Time Frame: EQ-5D-5L analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized ]

    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 patients 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.


Other Outcome Measures:
  1. Intracranial PFS according to RECIST v1.1 by Investigator assessment and blinded independent central review (BICR) [ Time Frame: Intracranial PFS based on Investigator assessment and BICR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized ]
    To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with brain metastases (BM) at baseline

  2. Intracranial ORR according to RECIST v1.1 by Investigator assessments and BICR [ Time Frame: Intracranial ORR based on Investigator assessment and BICR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized ]
    To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with BM at baseline

  3. Intracranial DoR according to RECIST v1.1 by Investigator assessment and BICR [ Time Frame: Intracranial DoR based on Investigator assessment and BICR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized ]
    To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with BM at baseline

  4. Intracranial DCR according to RECIST v1.1 by Investigator assessment and BICR [ Time Frame: Intracranial DCR based on Investigator assessment and BICR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized ]
    To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with BM at baseline

  5. Depth of intracranial response according to RECIST v1.1 by Investigator assessment and BICR [ Time Frame: Depth of intracranial response based on Investigator assessment and BICR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized ]
    To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with BM at baseline

  6. Time to intracranial response according to RECIST v1.1 by Investigator assessment and BICR [ Time Frame: Time to intracranial response analysis based on Investigator assessment and BICR will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized ]
    To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with BM at baseline

  7. PFS according to RECIST v1.1 by Investigator assessment [ Time Frame: PFS analysis will occur when OS maturity is observed at approximately 45 months from the first dosing date of lazertinib ]
    To assess the efficacy of lazertinib in the cross-over arm

  8. ORR according to RECIST v1.1 by Investigator assessments [ Time Frame: ORR analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized ]
    To assess the efficacy of lazertinib in the cross-over arm

  9. DoR according to RECIST v1.1 by Investigator assessments [ Time Frame: DoR analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized ]
    To assess the efficacy of lazertinib in the cross-over arm

  10. DCR according to RECIST v1.1 by Investigator assessments [ Time Frame: DCR analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized ]
    To assess the efficacy of lazertinib in the cross-over arm

  11. Depth of Response according to RECIST v1.1 by Investigator assessments [ Time Frame: Depth of Response analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized ]
    To assess the efficacy of lazertinib in the cross-over arm

  12. Time to Response according to RECIST v1.1 by Investigator assessments [ Time Frame: Time to Response analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized ]
    To assess the efficacy of lazertinib in the cross-over arm

  13. Change from baseline for EGFR mutation status in plasma samples [ Time Frame: EGFR mutation status in plasma samples analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized ]
    To compare plasma-derived cfDNA EGFR mutation status at baseline and at progression

  14. Change from baseline for EGFR mutation status in tumor samples [ Time Frame: EGFR mutation status in tumor samples analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized ]
    To compare the tumor sample EGFR mutation status at baseline and from an optional tumor sample taken at progression



Information from the National Library of Medicine

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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  • 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

Information from the National Library of Medicine

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


Contacts
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Contact: Dongmin Kim +82-2-828-0523 kdm27@yuhan.co.kr
Contact: Taewon An +82-2-828-0395 twan@yuhan.co.kr

Locations
Show Show 71 study locations
Sponsors and Collaborators
Yuhan Corporation
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Responsible Party: Yuhan Corporation
ClinicalTrials.gov Identifier: NCT04248829    
Other Study ID Numbers: YH25448-301
First Posted: January 30, 2020    Key Record Dates
Last Update Posted: October 9, 2020
Last Verified: October 2020
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.

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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
Keywords provided by Yuhan Corporation:
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
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Gefitinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action