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    Clinical Trial Results:
    A Phase I/II, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of YH25448 in Patients with EGFR Mutation Positive Advanced Non-Small Cell Lung Cancer (NSCLC)

    Summary
    EudraCT number
    2019-003106-28
    Trial protocol
    GB   ES  
    Global end of trial date
    14 Nov 2022

    Results information
    Results version number
    v1(current)
    This version publication date
    26 Nov 2023
    First version publication date
    26 Nov 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    73841937NSC2001
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT04075396
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Janssen Research & Development, LLC
    Sponsor organisation address
    920 Route 202, South Raritan, New Jersey, United States, 08869
    Public contact
    Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
    Scientific contact
    Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 Nov 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Nov 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this trial was to evaluate the safety, tolerability, and pharmacokinetics (PK) of YH25448 when given orally to subjects with epidermal growth factor receptor single activating mutation positive (EGFRm+) locally advanced or metastatic non-small cell lung cancer (NSCLC).
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    06 Nov 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 18
    Country: Number of subjects enrolled
    United Kingdom: 1
    Country: Number of subjects enrolled
    United States: 9
    Worldwide total number of subjects
    28
    EEA total number of subjects
    18
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    16
    From 65 to 84 years
    12
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 29 subjects from outside Korea were enrolled in the study, out of which 28 subjects received study treatment and none completed the study.

    Period 1
    Period 1 title
    Overall Period
    Is this the baseline period?
    Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Lazertinib 240 mg
    Arm description
    Subjects with epidermal growth factor receptor single activating mutation positive (EGFRm+) advanced non-small cell lung cancer (NSCLC) with or without asymptomatic brain metastasis received lazertinib tablet at a dose of 240 milligrams (mg) orally on Day 1 of Cycle 0, which spans 7 days, followed by a once daily dose in each subsequent 21-day treatment cycle, for a maximum duration of up to 32.7 months. Subjects were then followed up for safety for 28 days after the last dose of study treatment.
    Arm type
    Experimental

    Investigational medicinal product name
    Lazertinib
    Investigational medicinal product code
    Other name
    YH25448
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received lazertinib 240 mg tablet once daily.

    Arm title
    Lazertinib 320 mg
    Arm description
    Subjects with EGFRm+ advanced NSCLC with or without asymptomatic brain metastasis received lazertinib tablet at a dose of 320 mg orally on Day 1 of Cycle 0, which spans 7 days, followed by a once daily dose in each subsequent 21-day treatment cycle, for a maximum duration of up to 8.3 months. Subjects were then followed up for safety for 28 days after the last dose of study treatment.
    Arm type
    Experimental

    Investigational medicinal product name
    Lazertinib
    Investigational medicinal product code
    Other name
    YH25448
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received lazertinib 320 mg tablet once daily.

    Number of subjects in period 1
    Lazertinib 240 mg Lazertinib 320 mg
    Started
    15
    13
    Completed
    0
    0
    Not completed
    15
    13
         Adverse event, serious fatal
    11
    9
         Consent withdrawn by subject
    1
    2
         Protocol v 11.0 implementation
    3
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Lazertinib 240 mg
    Reporting group description
    Subjects with epidermal growth factor receptor single activating mutation positive (EGFRm+) advanced non-small cell lung cancer (NSCLC) with or without asymptomatic brain metastasis received lazertinib tablet at a dose of 240 milligrams (mg) orally on Day 1 of Cycle 0, which spans 7 days, followed by a once daily dose in each subsequent 21-day treatment cycle, for a maximum duration of up to 32.7 months. Subjects were then followed up for safety for 28 days after the last dose of study treatment.

    Reporting group title
    Lazertinib 320 mg
    Reporting group description
    Subjects with EGFRm+ advanced NSCLC with or without asymptomatic brain metastasis received lazertinib tablet at a dose of 320 mg orally on Day 1 of Cycle 0, which spans 7 days, followed by a once daily dose in each subsequent 21-day treatment cycle, for a maximum duration of up to 8.3 months. Subjects were then followed up for safety for 28 days after the last dose of study treatment.

    Reporting group values
    Lazertinib 240 mg Lazertinib 320 mg Total
    Number of subjects
    15 13 28
    Title for AgeCategorical
    Units: subjects
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    9 7 16
        From 65 to 84 years
    6 6 12
        85 years and over
    0 0 0
    Title for AgeContinuous
    Units: years
        arithmetic mean (standard deviation)
    60.6 ( 11.35 ) 63 ( 12.48 ) -
    Title for Gender
    Units: subjects
        Female
    9 8 17
        Male
    6 5 11

    End points

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    End points reporting groups
    Reporting group title
    Lazertinib 240 mg
    Reporting group description
    Subjects with epidermal growth factor receptor single activating mutation positive (EGFRm+) advanced non-small cell lung cancer (NSCLC) with or without asymptomatic brain metastasis received lazertinib tablet at a dose of 240 milligrams (mg) orally on Day 1 of Cycle 0, which spans 7 days, followed by a once daily dose in each subsequent 21-day treatment cycle, for a maximum duration of up to 32.7 months. Subjects were then followed up for safety for 28 days after the last dose of study treatment.

    Reporting group title
    Lazertinib 320 mg
    Reporting group description
    Subjects with EGFRm+ advanced NSCLC with or without asymptomatic brain metastasis received lazertinib tablet at a dose of 320 mg orally on Day 1 of Cycle 0, which spans 7 days, followed by a once daily dose in each subsequent 21-day treatment cycle, for a maximum duration of up to 8.3 months. Subjects were then followed up for safety for 28 days after the last dose of study treatment.

    Primary: Part D: Number of Subjects With Treatment-emergent Adverse Events (TEAEs)

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    End point title
    Part D: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) [1]
    End point description
    An adverse event (AE) is any untoward medical occurrence in a clinical study subject administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs were defined as AEs that started on or after the first dose of study medication and prior to 28-day follow-up period. All TEAEs including serious and non-serious events are reported in this endpoint. The safety analysis population included all subjects who received at least 1 dose of investigational product (IP).
    End point type
    Primary
    End point timeframe
    From Day 1 up to 32.7 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    15
    13
    Units: Subjects
    15
    13
    No statistical analyses for this end point

    Primary: Part D: Number of Subjects With Clinically Significant Abnormalities in Vital Signs

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    End point title
    Part D: Number of Subjects With Clinically Significant Abnormalities in Vital Signs [2]
    End point description
    Number of subjects with clinically significant abnormalities in vital signs were reported. Vital signs included pulse rate, systolic blood pressure, diastolic blood pressure, body temperature, height, weight, and body mass index (BMI). Baseline was defined as last non-missing measurement taken prior to reference start date. The safety analysis population included all subjects who received at least 1 dose of IP.
    End point type
    Primary
    End point timeframe
    Baseline up to 32.7 months
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    15
    13
    Units: Subjects
    0
    0
    No statistical analyses for this end point

    Primary: Part D: Number of Subjects With Clinically Significant Abnormalities in Physical Examination

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    End point title
    Part D: Number of Subjects With Clinically Significant Abnormalities in Physical Examination [3]
    End point description
    Number of subjects with clinically significant abnormalities in physical examination was reported. Physical examination included general appearance, skin, head and neck (including ears, eyes, nose and throat), respiratory, cardiovascular, abdomen, lymph nodes, thyroid, muscular-skeletal (including spine and extremities) and neurological systems. Baseline was defined as last non-missing measurement taken prior to reference start date. Safety analysis population: all subjects who received at least 1 dose of IP.
    End point type
    Primary
    End point timeframe
    Baseline up to 32.7 months
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    15
    13
    Units: Subjects
    11
    5
    No statistical analyses for this end point

    Primary: Part D: Number of Subjects With Greater Than or Equal to (>=) Grade 4 Toxicity in Laboratory Tests Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.03

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    End point title
    Part D: Number of Subjects With Greater Than or Equal to (>=) Grade 4 Toxicity in Laboratory Tests Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.03 [4]
    End point description
    Number of subjects with >=Grade 4 toxicity in laboratory tests based on NCI-CTCAE version 4.03 were reported. Safety laboratory assessments included clinical chemistry, hematology and urinalysis. As per NCI-CTCAE version 4.03: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. Baseline was defined as last non-missing measurement taken prior to reference start date. The safety analysis population included all subjects who received at least 1 dose of IP.
    End point type
    Primary
    End point timeframe
    Baseline up to 32.7 months
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    15
    13
    Units: Subjects
    2
    0
    No statistical analyses for this end point

    Primary: Part D: Number of Subjects With Clinically Significant Abnormalities in Electrocardiogram (ECG) Tests

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    End point title
    Part D: Number of Subjects With Clinically Significant Abnormalities in Electrocardiogram (ECG) Tests [5]
    End point description
    Number of subjects with clinically significant abnormalities in ECG tests were reported. ECG variables included heart rate, PR interval, RR interval, QRS interval, QT interval and Fridericia-corrected QT interval (QTcF). Baseline was defined as last non-missing measurement taken prior to reference start date. The safety analysis population included all subjects who received at least 1 dose of IP.
    End point type
    Primary
    End point timeframe
    Baseline up to 32.7 months
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    15
    13
    Units: Subjects
    1
    1
    No statistical analyses for this end point

    Primary: Part D: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-last]) for Single Dose of Lazertinib

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    End point title
    Part D: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-last]) for Single Dose of Lazertinib [6]
    End point description
    AUC(0-last) was defined as area under the plasma concentration-time curve from time zero to time of last quantifiable concentration. AUC(0-last) for single dose of lazertinib was reported in this endpoint. Pharmacokinetic (PK) analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    9
    Units: Hour*nanograms per millilitre(h*ng/mL)
        arithmetic mean (standard deviation)
    5907.56 ( 2218.84 )
    7664.99 ( 2057.13 )
    No statistical analyses for this end point

    Primary: Part D: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) for Single Dose of Lazertinib

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    End point title
    Part D: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) for Single Dose of Lazertinib [7]
    End point description
    AUC(0-infinity) was defined as area under the plasma concentration time curve from time zero to infinite time. AUC(0-infinity) for single dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    9
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    6504.88 ( 2542.12 )
    8869.21 ( 2642.17 )
    No statistical analyses for this end point

    Primary: Part D: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC[0-24]) for Single Dose of Lazertinib

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    End point title
    Part D: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC[0-24]) for Single Dose of Lazertinib [8]
    End point description
    AUC(0-24) was defined as area under the plasma concentration time curve from time zero to 24 hours. AUC(0-24) for single dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Pre-dose, 1, 2, 4, 10 and 24 hours post-dose on Day 1 of Cycle 0
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    9
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    3253.58 ( 916.67 )
    4097.34 ( 1261.96 )
    No statistical analyses for this end point

    Primary: Part D: Maximum Observed Plasma Concentration (Cmax) for Single Dose of Lazertinib

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    End point title
    Part D: Maximum Observed Plasma Concentration (Cmax) for Single Dose of Lazertinib [9]
    End point description
    Cmax was defined as maximum observed plasma concentration. Cmax for single dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    9
    Units: Nanograms per millilitre (ng/mL)
        arithmetic mean (standard deviation)
    441.04 ( 135.45 )
    524.13 ( 271.58 )
    No statistical analyses for this end point

    Primary: Part D: Apparent Terminal Elimination Rate Constant (lambda[z]) for Single Dose of Lazertinib

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    End point title
    Part D: Apparent Terminal Elimination Rate Constant (lambda[z]) for Single Dose of Lazertinib [10]
    End point description
    Lambda(z) was defined as terminal elimination rate constant. Lambda(z) for single dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    9
    Units: Per hour (1/h)
        arithmetic mean (standard deviation)
    0.02 ( 0.01 )
    0.01 ( 0.00 )
    No statistical analyses for this end point

    Primary: Part D: Apparent Terminal Half-Life (t1/2) for Single Dose of Lazertinib

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    End point title
    Part D: Apparent Terminal Half-Life (t1/2) for Single Dose of Lazertinib [11]
    End point description
    T1/2 was defined the time measured for the plasma concentration of a drug to decrease by half of its initial concentration. T1/2 for single dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    9
    Units: Hours
        median (full range (min-max))
    51.12 (18.75 to 70.71)
    63.98 (52.30 to 97.74)
    No statistical analyses for this end point

    Primary: Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Single Dose of Lazertinib

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    End point title
    Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Single Dose of Lazertinib [12]
    End point description
    Tmax was defined as time to reach the maximum observed plasma concentration. Tmax for single dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    9
    Units: Hours
        median (full range (min-max))
    2.00 (0.92 to 4.15)
    2.50 (1.07 to 4.00)
    No statistical analyses for this end point

    Primary: Part D: Apparent Plasma Clearance (CL/F) for Single Dose of Lazertinib

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    End point title
    Part D: Apparent Plasma Clearance (CL/F) for Single Dose of Lazertinib [13]
    End point description
    CL/F was defined as apparent plasma clearance. CL/F for single dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    9
    Units: Litres per hour (L/h)
        arithmetic mean (standard deviation)
    41.92 ( 15.56 )
    39.38 ( 12.96 )
    No statistical analyses for this end point

    Primary: Part D: Apparent Volume of Distribution (Vd/F) for Single Dose of Lazertinib

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    End point title
    Part D: Apparent Volume of Distribution (Vd/F) for Single Dose of Lazertinib [14]
    End point description
    Vd/F was defined as apparent volume of distribution. Vd/F for single dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    9
    Units: Litres
        arithmetic mean (standard deviation)
    2990.36 ( 1188.45 )
    3822.19 ( 984.29 )
    No statistical analyses for this end point

    Primary: Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Multiple Dose of Lazertinib

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    End point title
    Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Multiple Dose of Lazertinib [15]
    End point description
    Cmax,ss was defined as maximum observed plasma concentration at steady state. Cmax,ss for multiple dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Pre-dose on Day 1 of Cycle 1 up to pre-dose on Day 1 of Cycle 47
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    6
    Units: ng/mL
        arithmetic mean (standard deviation)
    509.92 ( 236.66 )
    632.00 ( 279.88 )
    No statistical analyses for this end point

    Primary: Part D: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the end of Dosing Interval at Steady State (AUCss[0-last]) for Multiple Dose of Lazertinib

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    End point title
    Part D: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the end of Dosing Interval at Steady State (AUCss[0-last]) for Multiple Dose of Lazertinib [16]
    End point description
    AUCss(0-last) was defined as area under the plasma concentration time curve from time zero to time of the end of dosing interval at steady state. AUCss(0-last) for multiple dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Pre-dose on Day 1 of Cycle 1 up to pre-dose on Day 1 of Cycle 47
    Notes
    [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    6
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    7025.10 ( 4181.22 )
    9249.58 ( 4924.51 )
    No statistical analyses for this end point

    Primary: Part D: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) for Multiple Dose of Lazertinib

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    End point title
    Part D: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) for Multiple Dose of Lazertinib [17]
    End point description
    Tmax,ss was defined as time to reach maximum observed plasma concentration at steady state. Tmax,ss for multiple dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Pre-dose on Day 1 of Cycle 1 up to pre-dose on Day 1 of Cycle 47
    Notes
    [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    6
    Units: Hours
        median (full range (min-max))
    3.15 (1.75 to 9.00)
    3.97 (2.22 to 9.00)
    No statistical analyses for this end point

    Primary: Part D: Accumulation Ratio (Rac) for Multiple Dose of Lazertinib

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    End point title
    Part D: Accumulation Ratio (Rac) for Multiple Dose of Lazertinib [18]
    End point description
    Accumulation ratio was calculated as AUCss(0-last) divided by AUC(0-24), where AUCss(0-last) was defined as area under the plasma concentration time curve from time zero to end of dosing interval at steady state and AUC(0-24) was defined area under the plasma concentration time curve from time zero to 24 hours time. Rac for multiple dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Pre-dose, 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 0 and Cycle 2
    Notes
    [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    11
    4
    Units: Ratio
        arithmetic mean (standard deviation)
    2.26 ( 0.61 )
    2.36 ( 1.08 )
    No statistical analyses for this end point

    Primary: Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 1

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    End point title
    Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 1 [19]
    End point description
    Ctrough was defined as pre-dose plasma concentration. Ctrough for multiple dose of lazertinib at Cycle 1 Day 1 was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Pre-dose on Day 1 of Cycle 1
    Notes
    [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    9
    Units: ng/mL
        arithmetic mean (standard deviation)
    6.41 ( 4.55 )
    10.91 ( 5.99 )
    No statistical analyses for this end point

    Primary: Part D: Apparent Plasma Clearance at Steady State (CLss/F) for Multiple Dose of Lazertinib

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    End point title
    Part D: Apparent Plasma Clearance at Steady State (CLss/F) for Multiple Dose of Lazertinib [20]
    End point description
    CLss/F was defined as apparent plasma clearance at steady state. CLss/F for multiple dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Pre-dose on Day 1 of Cycle 1 up to pre-dose on Day 1 of Cycle 47
    Notes
    [20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    6
    Units: Litres per hour (L/h)
        arithmetic mean (standard deviation)
    44.25 ( 21.39 )
    50.10 ( 37.21 )
    No statistical analyses for this end point

    Primary: Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 8

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    End point title
    Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 8 [21]
    End point description
    Ctrough was defined as pre-dose plasma concentration. Ctrough for multiple dose of lazertinib at Cycle 1 Day 8 was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Pre-dose on Day 8 of Cycle 1
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    14
    10
    Units: ng/mL
        arithmetic mean (standard deviation)
    154.62 ( 87.60 )
    225.47 ( 168.22 )
    No statistical analyses for this end point

    Primary: Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 15

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    End point title
    Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 15 [22]
    End point description
    Ctrough was defined as pre-dose plasma concentration. Ctrough for multiple dose of lazertinib at Cycle 1 Day 15 was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Pre-dose on Day 15 of Cycle 1
    Notes
    [22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    9
    Units: ng/mL
        arithmetic mean (standard deviation)
    177.40 ( 99.23 )
    263.74 ( 145.61 )
    No statistical analyses for this end point

    Secondary: Part D: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-last]) of Metabolite M7 After Single Dose of Lazertinib

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    End point title
    Part D: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-last]) of Metabolite M7 After Single Dose of Lazertinib
    End point description
    AUC(0-last) was defined as area under the plasma concentration-time curve from time zero to time of last quantifiable concentration. AUC(0-last) of metabolite M7 after single dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    9
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    216.350 ( 126.357 )
    208.908 ( 128.968 )
    No statistical analyses for this end point

    Secondary: Part D: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of Metabolite M7 After Single Dose of Lazertinib

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    End point title
    Part D: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of Metabolite M7 After Single Dose of Lazertinib
    End point description
    AUC(0-infinity) was defined as area under the plasma concentration time curve from time zero to infinite time. AUC(0-infinity) of metabolite M7 after single dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    12
    7
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    281.172 ( 144.163 )
    263.373 ( 166.254 )
    No statistical analyses for this end point

    Secondary: Part D: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Metabolite M7 After Single Dose of Lazertinib

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    End point title
    Part D: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Metabolite M7 After Single Dose of Lazertinib
    End point description
    AUC(0-24) was defined as area under the plasma concentration time curve from time zero to 24 hours. AUC(0-24) of metabolite M7 after single dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 1, 2, 4, 10 and 24 hours post-dose on Day 1 of Cycle 0
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    9
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    86.692 ( 52.492 )
    74.523 ( 33.137 )
    No statistical analyses for this end point

    Secondary: Part D: Maximum Observed Plasma Concentration (Cmax) of Metabolite M7 After Single Dose of Lazertinib

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    End point title
    Part D: Maximum Observed Plasma Concentration (Cmax) of Metabolite M7 After Single Dose of Lazertinib
    End point description
    Cmax was defined as maximum observed plasma concentration. Cmax of metabolite M7 after single dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    9
    Units: ng/mL
        arithmetic mean (standard deviation)
    5.838 ( 3.946 )
    4.774 ( 2.257 )
    No statistical analyses for this end point

    Secondary: Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolite M7 After Single Dose of Lazertinib

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    End point title
    Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolite M7 After Single Dose of Lazertinib
    End point description
    Tmax was defined as time to reach the maximum observed plasma concentration. Tmax of metabolite M7 after single dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    9
    Units: Hours
        median (full range (min-max))
    4.020 (2.070 to 10.080)
    4.150 (3.080 to 22.350)
    No statistical analyses for this end point

    Secondary: Part D: Apparent Terminal Half-Life (t1/2) of Metabolite M7 After Single Dose of Lazertinib

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    End point title
    Part D: Apparent Terminal Half-Life (t1/2) of Metabolite M7 After Single Dose of Lazertinib
    End point description
    T1/2 was defined the time measured for the plasma concentration of a drug to decrease by half of its initial concentration. T1/2 of metabolite M7 after single dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    12
    7
    Units: Hours (h)
        median (full range (min-max))
    41.205 (18.042 to 86.989)
    50.019 (13.256 to 74.867)
    No statistical analyses for this end point

    Secondary: Part D: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the end of Dosing Interval at Steady State (AUCss[0-last]) of Metabolite M7 After Multiple Dose of Lazertinib

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    End point title
    Part D: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the end of Dosing Interval at Steady State (AUCss[0-last]) of Metabolite M7 After Multiple Dose of Lazertinib
    End point description
    AUCss(0-last) was defined as area under the plasma concentration-time curve from time zero to time of the end of dosing interval at steady state. AUCss(0-last) of metabolite M7 after multiple dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose on Day 1 of Cycle 1 up to pre-dose on Day 1 of Cycle 47
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    6
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    148.335 ( 89.794 )
    168.765 ( 159.476 )
    No statistical analyses for this end point

    Secondary: Part D: Metabolic Ratio (MR) of Metabolite M7 and Lazertinib After Single Dose of Lazertinib

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    End point title
    Part D: Metabolic Ratio (MR) of Metabolite M7 and Lazertinib After Single Dose of Lazertinib
    End point description
    MR was defined as ratio of the AUC(0-infinity) of metabolite M7 and AUC(0-infinity) of lazertinib, where AUC(0-infinity) was defined as area under the plasma concentration time curve from time zero to infinite time. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    12
    7
    Units: Ratio
        arithmetic mean (standard deviation)
    0.042 ( 0.022 )
    0.027 ( 0.015 )
    No statistical analyses for this end point

    Secondary: Part D: Apparent Terminal Elimination Rate Constant (lambda [z]) of Metabolite M7 After Single Dose of Lazertinib

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    End point title
    Part D: Apparent Terminal Elimination Rate Constant (lambda [z]) of Metabolite M7 After Single Dose of Lazertinib
    End point description
    Lambda(z) was defined as terminal elimination rate constant. Lambda(z) of metabolite M7 after single dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    12
    7
    Units: Per hour (1/h)
        arithmetic mean (standard deviation)
    0.017 ( 0.008 )
    0.021 ( 0.016 )
    No statistical analyses for this end point

    Secondary: Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib

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    End point title
    Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib
    End point description
    Cmax,ss was defined as maximum observed plasma concentration at steady state. Cmax,ss of metabolite M7 after multiple dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose on Day 1 of Cycle 1 up to pre-dose on Day 1 of Cycle 47
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    6
    Units: ng/mL
        arithmetic mean (standard deviation)
    7.866 ( 4.213 )
    8.319 ( 7.418 )
    No statistical analyses for this end point

    Secondary: Part D: Time for Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib

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    End point title
    Part D: Time for Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib
    End point description
    Tmax,ss was defined as time to reach the maximum observed plasma concentration at steady state. Tmax,ss of metabolite M7 after multiple dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose on Day 1 of Cycle 1 up to pre-dose on Day 1 of Cycle 47
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    6
    Units: Hours
        median (full range (min-max))
    6.330 (2.250 to 9.000)
    4.350 (3.930 to 24.070)
    No statistical analyses for this end point

    Secondary: Part D: Accumulation Ratio (Rac) of Metabolite M7 After Multiple Dose of Lazertinib

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    End point title
    Part D: Accumulation Ratio (Rac) of Metabolite M7 After Multiple Dose of Lazertinib
    End point description
    Accumulation ratio was calculated as AUCss(0-last) divided by AUC(0-24), where AUCss(0-last) was defined as area under the plasma concentration time curve from time zero to end of dosing interval and AUC(0-24) was defined area under the plasma concentration time curve from time zero to 24 hours. Rac of metabolite M7 after multiple dose of lazertinib was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 1, 2, 4, 10 and 24 hours post dose on Day 1 Cycle 0 and Cycle 2
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    11
    4
    Units: Ratio
        arithmetic mean (standard deviation)
    1.976 ( 0.617 )
    2.270 ( 1.300 )
    No statistical analyses for this end point

    Secondary: Part D: Trough Concentrations (Ctrough) of Metabolite M7 After Multiple Dose of Lazertinib at Days 1, 8, and 15 of Cycle 1

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    End point title
    Part D: Trough Concentrations (Ctrough) of Metabolite M7 After Multiple Dose of Lazertinib at Days 1, 8, and 15 of Cycle 1
    End point description
    Ctrough was defined as pre-dose plasma concentration. Ctrough of Metabolite M7 after multiple dose of lazertinib at Days 1, 8 and 15 of Cycle 1 was reported in this endpoint. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint and 'n' (number analysed) refers to all subjects evaluable at time points.
    End point type
    Secondary
    End point timeframe
    Pre-dose on Days 1, 8 and 15 of Cycle 1
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    14
    10
    Units: ng/mL
    arithmetic mean (standard deviation)
        Day 1 Cycle 1 (n = 13, 9)
    0.257 ( 0.237 )
    0.358 ( 0.321 )
        Day 8 Cycle 1 (n = 14, 10)
    4.928 ( 3.005 )
    5.791 ( 4.650 )
        Day 15 Cycle 1 (n = 13, 9)
    5.356 ( 3.604 )
    6.340 ( 4.741 )
    No statistical analyses for this end point

    Secondary: Part D: Metabolic Ratio at Steady State (MRss) of Metabolite M7 and Lazertinib After Multiple Dose of Lazertinib

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    End point title
    Part D: Metabolic Ratio at Steady State (MRss) of Metabolite M7 and Lazertinib After Multiple Dose of Lazertinib
    End point description
    MRss was defined as ratio of the AUCss(0-last) of metabolite M7 and AUCss(0-last) of lazertinib, where AUCss(0-last) was defined as area under the plasma concentration time curve from time zero to time of end of dosing interval at steady state. PK analysis population included all subjects who had at least 1 measurable concentration collected post dose. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose on Day 1 of Cycle 1 up to pre-dose on Day 1 of Cycle 47
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    13
    6
    Units: Ratio
        arithmetic mean (standard deviation)
    0.021 ( 0.006 )
    0.016 ( 0.009 )
    No statistical analyses for this end point

    Secondary: Objective Response Rate (ORR)

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    End point title
    Objective Response Rate (ORR)
    End point description
    ORR: percentage of subjects who had at least 1 confirmed partial or complete response (PR/CR) as per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 prior to disease progression/recurrence. CR: disappearance of target and non-target lesions and normalization of tumour markers. Pathological lymph nodes must have short axis measures <10 millimetre (mm). PR: >=30% decrease in sum of measures (longest diameter for tumour lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-progressive disease (PD). PD: >=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative 20% increase, sum must also demonstrate an absolute increase of >=5mm. Appearance of one/more new lesions was considered progression. Evaluable for response population: all subjects in safety analysis population who had a baseline RECIST version 1.1 assessment.
    End point type
    Secondary
    End point timeframe
    Up to 33.7 months
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    15
    13
    Units: Percentage of subjects
        number (confidence interval 95%)
    26.7 (4.3 to 49.0)
    7.7 (0.0 to 22.2)
    No statistical analyses for this end point

    Secondary: Duration of Response (DoR)

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    End point title
    Duration of Response (DoR)
    End point description
    DOR: time between date of first documented confirmed response (PR/CR) and date of first documented progression or death, whichever occurred first. CR: disappearance of target and non-target lesions and normalization of tumour markers. Pathological lymph nodes short axis measures <10mm. PR: >=30% decrease in sum of measures (tumour lesions-longest diameter and nodes-short axis)of target lesions, taking as reference baseline sum of diameters. PD: >=20% increase in sum of diameters of measured lesions taking as references smallest sum of diameters recorded on study(including baseline),absolute increase of >=5mm/appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions. Evaluable for response population: all subjects in safety analysis population who had baseline RECIST version 1.1 assessment. N=number of subjects evaluable for this endpoint. 99999=median is not reached; lower and upper limit of confidence interval could not be calculated for 1 subject.
    End point type
    Secondary
    End point timeframe
    Up to 33.7 months
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    4
    1
    Units: Months
        median (confidence interval 95%)
    99999 (5.6 to 99999)
    2.8 (-99999 to 99999)
    No statistical analyses for this end point

    Secondary: Disease Control Rate (DCR)

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    End point title
    Disease Control Rate (DCR)
    End point description
    DCR: percentage of subjects with a best overall response (BOR), extracranial and intracranial response of CR, PR or stable disease(SD). As per RECIST version 1.1 CR: disappearance of target and non-target lesions and normalization of tumour markers. Pathological lymph nodes must have short axis measures <10mm. PR: >=30% decrease in sum of measures (longest diameter for tumour lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD: >=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative 20% increase, sum must also demonstrate >=5mm absolute increase. Appearance of one/more new lesions was considered progression. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Evaluable for response population: all subjects in safety analysis population who had baseline RECIST version 1.1 assessment.
    End point type
    Secondary
    End point timeframe
    Up to 33.7 months
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    15
    13
    Units: Percentage of subjects
        number (confidence interval 95%)
    60.0 (35.2 to 84.8)
    53.8 (26.7 to 80.9)
    No statistical analyses for this end point

    Secondary: Percentage Change from Baseline in Tumour Size

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    End point title
    Percentage Change from Baseline in Tumour Size
    End point description
    Tumour size was defined as the sum lengths of the longest diameters of the target lesion. Percentage change in tumour size was determined for subjects with measurable disease at baseline. Baseline for RECIST was defined as the last evaluable assessment prior to starting treatment. Evaluable for response population: all subjects in safety analysis population who had a baseline RECIST version 1.1 assessment. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to 33.7 months
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    14
    12
    Units: Percentage change in tumour size
        arithmetic mean (standard deviation)
    -5.37 ( 37.68 )
    9.56 ( 42.89 )
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS)

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    End point title
    Progression Free Survival (PFS)
    End point description
    PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST version 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion. The safety analysis population included all subjects who received at least 1 dose of IP. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to 33.7 months
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    11
    11
    Units: Months
        median (full range (min-max))
    3.1 (1.3 to 11.2)
    4.2 (0.0 to 7.7)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    Overall Survival (OS)
    End point description
    OS was defined as the time from the date of first dose to date of death due to any cause. The safety analysis population included all subjects who received at least 1 dose of IP. Here 'N' (number of subjects analysed) refers to the number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to 33.7 months
    End point values
    Lazertinib 240 mg Lazertinib 320 mg
    Number of subjects analysed
    11
    9
    Units: Months
        median (full range (min-max))
    9.1 (2.6 to 24.3)
    7.7 (3.4 to 12.3)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All cause mortality: Day 1 up to 33.7 months; Serious and other adverse events: Day 1 up to 32.7 months
    Adverse event reporting additional description
    The safety analysis population included all subjects who received at least 1 dose of investigational product (IP).
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Lazertinib 320 mg
    Reporting group description
    Subjects with EGFRm+ advanced NSCLC with or without asymptomatic brain metastasis received lazertinib tablet at a dose of 320 mg orally on Day 1 of Cycle 0, which spans 7 days, followed by a once daily dose in each subsequent 21-day treatment cycle, for a maximum duration of up to 8.3 months. Subjects were then followed up for safety for 28 days after the last dose of study treatment

    Reporting group title
    Lazertinib 240 mg
    Reporting group description
    Subjects with epidermal growth factor receptor single activating mutation positive (EGFRm+) advanced non-small cell lung cancer (NSCLC) with or without asymptomatic brain metastasis received lazertinib tablet at a dose of 240 milligrams (mg) orally on Day 1 of Cycle 0, which spans 7 days, followed by a once daily dose in each subsequent 21-day treatment cycle, for a maximum duration of up to 32.7 months. Subjects were then followed up for safety for 28 days after the last dose of study treatment.

    Serious adverse events
    Lazertinib 320 mg Lazertinib 240 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 13 (46.15%)
    10 / 15 (66.67%)
         number of deaths (all causes)
    9
    11
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant Neoplasm Progression
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep Vein Thrombosis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Adrenalectomy
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cognitive Disorder
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular Accident
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    2 / 13 (15.38%)
    3 / 15 (20.00%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary Embolism
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 15 (13.33%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Musculoskeletal and connective tissue disorders
    Bone Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular Weakness
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in Extremity
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pathological Fracture
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Covid-19
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper Respiratory Tract Infection
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Lazertinib 320 mg Lazertinib 240 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 13 (84.62%)
    15 / 15 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Vascular disorders
    Deep Vein Thrombosis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Hot Flush
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Oedema Peripheral
         subjects affected / exposed
    2 / 13 (15.38%)
    3 / 15 (20.00%)
         occurrences all number
    2
    3
    Medical Device Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Induration
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Gait Disturbance
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
         occurrences all number
    1
    2
    Fatigue
         subjects affected / exposed
    3 / 13 (23.08%)
    1 / 15 (6.67%)
         occurrences all number
    4
    1
    Chest Pain
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    Asthenia
         subjects affected / exposed
    2 / 13 (15.38%)
    3 / 15 (20.00%)
         occurrences all number
    2
    4
    Reproductive system and breast disorders
    Benign Prostatic Hyperplasia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
         occurrences all number
    0
    3
    Dysphonia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Dyspnoea
         subjects affected / exposed
    3 / 13 (23.08%)
    4 / 15 (26.67%)
         occurrences all number
    3
    4
    Epistaxis
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    Pleural Effusion
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Pulmonary Embolism
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    2
    Psychiatric disorders
    Affect Lability
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Confusional State
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Depressed Mood
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Disorientation
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Insomnia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Sleep Disorder
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Alanine Aminotransferase Increased
         subjects affected / exposed
    2 / 13 (15.38%)
    3 / 15 (20.00%)
         occurrences all number
    2
    8
    Amylase Increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    1 / 13 (7.69%)
    4 / 15 (26.67%)
         occurrences all number
    1
    11
    Blood Alkaline Phosphatase Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    3 / 15 (20.00%)
         occurrences all number
    0
    3
    Blood Bilirubin Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    3
    Blood Creatinine Increased
         subjects affected / exposed
    3 / 13 (23.08%)
    2 / 15 (13.33%)
         occurrences all number
    3
    2
    Blood Magnesium Decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    2
    Blood Sodium Decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Lymphocyte Count Decreased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Neutrophil Count Decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    3 / 15 (20.00%)
         occurrences all number
    0
    3
    Platelet Count Decreased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Troponin I Increased
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    Troponin Increased
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    Weight Decreased
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    White Blood Cell Count Decreased
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    Cardiac disorders
    Angina Pectoris
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Nervous system disorders
    Amnesia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Dysarthria
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Epilepsy
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    3 / 13 (23.08%)
    1 / 15 (6.67%)
         occurrences all number
    3
    1
    Hypoaesthesia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Memory Impairment
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Neuropathy Peripheral
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Neurotoxicity
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Paraesthesia
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 15 (13.33%)
         occurrences all number
    2
    2
    Peripheral Sensory Neuropathy
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Sciatica
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Taste Disorder
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Tremor
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Dizziness
         subjects affected / exposed
    0 / 13 (0.00%)
    3 / 15 (20.00%)
         occurrences all number
    0
    3
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 15 (13.33%)
         occurrences all number
    2
    2
    Thrombocytopenia
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    Leukopenia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Anaemia
         subjects affected / exposed
    2 / 13 (15.38%)
    7 / 15 (46.67%)
         occurrences all number
    5
    12
    Lymphopenia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    2
    Ear and labyrinth disorders
    Hypoacusis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Vertigo Positional
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Eye disorders
    Vision Blurred
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    Dry Eye
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
         occurrences all number
    1
    2
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
         occurrences all number
    0
    2
    Abdominal Pain
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Dysphagia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Diarrhoea
         subjects affected / exposed
    7 / 13 (53.85%)
    7 / 15 (46.67%)
         occurrences all number
    12
    11
    Dry Mouth
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Dyspepsia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Vomiting
         subjects affected / exposed
    3 / 13 (23.08%)
    2 / 15 (13.33%)
         occurrences all number
    4
    2
    Glossitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Gingival Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Nausea
         subjects affected / exposed
    8 / 13 (61.54%)
    4 / 15 (26.67%)
         occurrences all number
    9
    5
    Skin and subcutaneous tissue disorders
    Skin Lesion
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Skin Hyperpigmentation
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Dermatitis Acneiform
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Dry Skin
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    Erythema
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Folliculitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Onychoclasis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Onychomadesis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Papule
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Paronychia
         subjects affected / exposed
    0 / 13 (0.00%)
    3 / 15 (20.00%)
         occurrences all number
    0
    6
    Pruritus
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    Rash
         subjects affected / exposed
    3 / 13 (23.08%)
    4 / 15 (26.67%)
         occurrences all number
    4
    4
    Rash Macular
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Rash Maculo-Papular
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    2
    Solar Dermatitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Chromaturia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Pollakiuria
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Polyuria
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 13 (23.08%)
    2 / 15 (13.33%)
         occurrences all number
    3
    2
    Back Pain
         subjects affected / exposed
    3 / 13 (23.08%)
    3 / 15 (20.00%)
         occurrences all number
    3
    3
    Muscle Rigidity
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Muscular Weakness
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 15 (13.33%)
         occurrences all number
    1
    2
    Musculoskeletal Chest Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Myalgia
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    Pain in Extremity
         subjects affected / exposed
    2 / 13 (15.38%)
    3 / 15 (20.00%)
         occurrences all number
    2
    3
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Hordeolum
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Covid-19
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Conjunctivitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Bronchitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Appetite Disorder
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Decreased Appetite
         subjects affected / exposed
    3 / 13 (23.08%)
    2 / 15 (13.33%)
         occurrences all number
    5
    2
    Hypercalcaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
         occurrences all number
    0
    2
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
         occurrences all number
    0
    2
    Hyperkalaemia
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 15 (20.00%)
         occurrences all number
    1
    4
    Hypermagnesaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
         occurrences all number
    0
    2
    Hyponatraemia
         subjects affected / exposed
    0 / 13 (0.00%)
    3 / 15 (20.00%)
         occurrences all number
    0
    3
    Polydipsia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    30 Jul 2019
    The overall reason for this amendment was to change the standard for causality assessment, time schedule for vital sign and electrocardiogram (ECG) assessment for Part D, and reflect other changes to unify protocol for Korea and outside Korea. Sponsor name for Part D was changed from Yuhan to Janssen.
    13 Apr 2021
    The overall reason for amendment was to re-insert safety assessments for Part D after primary database lock (DBL) (19 Apr 2021) to allow protocol consistency across part D countries following a request from the Medicines and Healthcare Products Regulatory Agency (MHRA).
    19 Nov 2021
    The overall reason for this amendment was to removed requirement for long-term follow-up of subjects in Part D.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Study Parts A, B, and C were sponsored by Yuhan Corporation under protocol identifier (ID) YH25448-201 and Part D was sponsored by Janssen Research and Development, LLC under protocol ID 73841937NSC2001. Therefore, only Part D results are reported.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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