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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
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

73841937NSC2001

ISRCTN number

US NCT number

NCT04075396

WHO universal trial number (UTN)

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

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

14 Nov 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

14 Nov 2022

Was the trial ended prematurely?

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

Independent data monitoring committee (IDMC) involvement?

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

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

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 title

Overall Period

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

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.

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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Reporting group title

Lazertinib 240 mg

Reporting group description

Reporting group title

Lazertinib 320 mg

Reporting group description

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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Reporting group title

Lazertinib 240 mg

Reporting group description

Reporting group title

Lazertinib 320 mg

Reporting group description

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 Electrocardiogram (ECG) Tests

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End point title

Part D: Number of Subjects With Clinically Significant Abnormalities in Electrocardiogram (ECG) Tests ^[3]

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
[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	1	1

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 Physical Examination

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End point title

Part D: Number of Subjects With Clinically Significant Abnormalities in Physical Examination ^[5]

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
[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	11	5

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 ^[6]

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
[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: 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: 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 ^[7]

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
[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: Hournanograms per millilitre(hng/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 ^[8]

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
[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)	6504.88 ± 2542.12	8869.21 ± 2642.17

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 ^[9]

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
[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: 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: 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 ^[10]

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
[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: 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 ^[11]

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
[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: 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 ^[12]

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
[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))	51.12 (18.75 to 70.71)	63.98 (52.30 to 97.74)

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 ^[13]

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
[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	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 ^[14]

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
[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	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: 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 ^[15]

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
[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	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 ^[16]

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
[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	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: 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: 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 ^[19]

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
[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	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 1

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End point title

Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 1 ^[20]

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
[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	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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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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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 name

MedDRA

Dictionary version

26.0

Reporting group title

Lazertinib 320 mg

Reporting group description

Reporting group title

Lazertinib 240 mg

Reporting group description

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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Were there any global substantial amendments to the protocol? Yes

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.

Were there any global interruptions to the trial? No

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.

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Clinical trials

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)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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)