Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
The main purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of Lazertinib when given orally to participants with epidermal growth factor receptor single activating mutation positive (EGFRm+) locally advanced or metastatic Non Small Cell Lung Cancer (NSCLC).
Detailed description
One-third of all cancer deaths worldwide are still caused by lung cancer and non-small-cell lung cancer (NSCLC). Lazertinib is an oral, highly potent, mutant-selective and irreversible epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKIs) targets both the T790M mutation and activating EGFR mutations while sparing wild type-EGFR. The study will be conducted in participants with EGFR mutation positive advanced non-small cell lung cancer (NSCLC). Study Parts A, B, and C are sponsored by Yuhan Corporation under protocol identifier YH25448-201 (ClinicalTrials.gov Identifier: NCT03046992), and Study Part D is sponsored by Janssen Research and Development, LLC under protocol identifier 73841937NSC2001. In Part D, Lazertinib will be given to participants outside Korea, including Caucasians, in order to evaluate safety, tolerability, efficacy (including tumor response) and Pharmacokinetics (PK) in participants outside of Korea. The duration of this study will be up to 2 years. Study treatment should be held in all participants with suspected (symptomatic) or documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive disease, until recovery from all infection related symptoms, and documented to be negative for SARS-CoV-2.
Interventions
DRUGLazertinib
Participants will receive Lazertinib tablets once daily.
Sponsors
Yuhan Corporation
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Females should agree to use adequate contraceptive measure, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of following criteria at screening; Post-menopausal defined as aged more than 50 years and ameorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments; Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation; Women under 50 years old would be considered postmenopausal if they have been ameorrhoeic for at least 12 months following cessation of exogenous hormonal treatment, and have serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in postmenopausal range for the institution * Male participants who have not undergone a vasectomy must agree to use barrier contraception that is, condoms, and refrain from donating sperm until 3 months after last drug is taken * During the study, and for 3 months after receiving the last dose of study drug, female participants must agree not to donate eggs (ova, oocytes) and male participants must agree not to donate sperm for the purposes of assisted reproduction * In Part D: Participants outside Korea with histologically or cytologically (that is, using pleural effusion, ascites) confirmed Non-Small Cell Lung Cancer (NSCLC) with previously diagnosed epidermal growth factor receptor single activating mutation positive (EGFRm+), and who have had progressive disease on prior epidermal growth factor receptor- Tyrosine kinase inhibitor (EGFR-TKI) therapy * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 3 months
Exclusion criteria
* An unapproved investigational product from another clinical study within 30 days of the first dose of study treatment * Treatment with an EGFR TKIs (example: erlotinib or gefitinib) within 8 days or approximately 5x half-life, whichever is the longer, of the first dose of study treatment or other investigational products within approved indication of marketed product (if sufficient wash-out time has not occurred due to schedule or PK properties, an alternative appropriate wash-out time based on known duration of time to reversibility of drug related adverse events could be agreed upon by sponsor and the Investigator) * Any cytotoxic chemotherapy or other anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen within 14 days of the first dose of study treatment * Symptomatic spinal cord compression (if steroid treatment is not required within at least 2 weeks prior to the start of the study treatment then the participant may be enrolled) * Brain metastases with symptomatic and/or requiring emergency treatment (example; Steroid for at least 2 weeks prior to start of study treatment)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 15 | Pre-dose on Day 15 of Cycle 1 | Ctrough was defined as pre-dose plasma concentration. Ctrough for multiple dose of lazertinib at Cycle 1 Day 15 was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From Day 1 up to 14 months | An adverse event (AE) is any untoward medical occurrence in a clinical study participant 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 outcome measure. |
| Part D: Number of Participants With Clinically Significant Abnormalities in Physical Examination | From Day 1 up to 14 months | Number of participants with clinically significant abnormalities in physical examination were 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. |
| Part D: Number of Participants 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 (v) 4.03 | From Day 1 up to 14 months | Safety laboratory assessments included clinical chemistry, hematology and urinalysis. Grading was done 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. |
| Part D: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Tests | From Day 1 up to 14 months | Number of participants with clinically significant abnormalities in electrocardiogram (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. |
| 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 | Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0 | 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 outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method. |
| Part D: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) for Single Dose of Lazertinib | Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0 | 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 outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC[0-24]) for Single Dose of Lazertinib | Pre-dose, 1, 2, 4, 10 and 24 hours post-dose on Day 1 of Cycle 0 | 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 outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Maximum Observed Plasma Concentration (Cmax) for Single Dose of Lazertinib | Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0 | Cmax was defined as maximum observed plasma concentration. Cmax for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Single Dose of Lazertinib | Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0 | Tmax was defined as time to reach the maximum observed plasma concentration. Tmax for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Apparent Terminal Half-Life (t1/2) for Single Dose of Lazertinib | Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0 | 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 outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Apparent Terminal Elimination Rate Constant (Lambda[z]) for Single Dose of Lazertinib | Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0 | Lambda(z) was defined as terminal elimination rate constant. Lambda(z) for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Apparent Plasma Clearance (CL/F) for Single Dose of Lazertinib | Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0 | CL/F was defined as apparent plasma clearance. CL/F for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Apparent Volume of Distribution (Vd/F) for Single Dose of Lazertinib | Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0 | Vd/F was defined as apparent volume of distribution. Vd/F for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| 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 | Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2 | AUCss(0-last) was defined as area under the plasma concentration time curve from time zero to end of dosing interval at steady state. AUCss(0-last) for multiple dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Multiple Dose of Lazertinib | Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2 | Cmax,ss was defined as maximum observed plasma concentration at steady state. Cmax,ss for multiple dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) for Multiple Dose of Lazertinib | Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2 | 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 outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Accumulation Ratio (Rac) for Multiple Dose of Lazertinib | Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2 | 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 outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Apparent Plasma Clearance at Steady State (CLss/F) for Multiple Dose of Lazertinib | Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2 | CLss/F was defined as apparent plasma clearance at steady state. CLss/F for multiple dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 1 | Pre-dose on Day 1 of Cycle 1 | Ctrough was defined as pre-dose plasma concentration. Ctrough for multiple dose of lazertinib at Cycle 1 Day 1 was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 8 | Pre-dose on Day 8 of Cycle 1 | Ctrough was defined as pre-dose plasma concentration. Ctrough for multiple dose of lazertinib at Cycle 1 Day 8 was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Number of Participants With Clinically Significant Abnormalities in Vital Signs | From Day 1 up to 14 months | Number of participants 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0 | 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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method. |
| 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 | Pre-dose, 1, 2, 4, 10 and 24 hours post-dose on Day 1 of Cycle 0 | 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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Maximum Observed Plasma Concentration (Cmax) of Metabolite M7 After Single Dose of Lazertinib | Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0 | Cmax was defined as maximum observed plasma concentration. Cmax of metabolite M7 after single dose of lazertinib was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolite M7 After Single Dose of Lazertinib | Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0 | 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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Apparent Terminal Half-Life (t1/2) of Metabolite M7 After Single Dose of Lazertinib | Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0 | 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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Apparent Terminal Elimination Rate Constant (Lambda [z]) of Metabolite M7 After Single Dose of Lazertinib | Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0 | Lambda(z) was defined as terminal elimination rate constant. Lambda(z) of metabolite M7 after single dose of lazertinib was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Metabolic Ratio (MR) of Metabolite M7 and Lazertinib After Single Dose of Lazertinib | Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0 | 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. The concentrations of metabolite M7 and lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| 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 | Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2 | 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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib | Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2 | 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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib | Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2 | 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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Accumulation Ratio (Rac) of Metabolite M7 After Multiple Dose of Lazertinib | Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2 | 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. Rac of metabolite M7 after multiple dose of lazertinib was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Trough Concentrations (Ctrough) of Metabolite M7 After Multiple Dose of Lazertinib at Days 1, 8 and 15 of Cycle 1 | Pre-dose on Days 1, 8 and 15 of Cycle 1 | 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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Part D: Metabolic Ratio at Steady State (MRss) of Metabolite M7 and Lazertinib After Multiple Dose of Lazertinib | Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2 | 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. The concentrations of metabolite M7 and lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method. |
| Objective Response Rate (ORR) | Up to 33.7 months | ORR was defined as percentage of participants who had at least 1 confirmed partial or complete response (PR or CR) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 prior to disease progression or recurrence. CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (\<) 10 millimeter (mm). PR was defined as greater than or equal to (\>=) 30 percent (%) decrease in sum of measures (longest diameter for tumor 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 was defined as \>=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 \>=5 mm. Appearance of one or more new lesions was considered progression. |
| Duration of Response (DoR) | Up to 33.7 months | DOR was defined as time between date of first documented confirmed response (PR/CR) and date of first documented progression or death, whichever occurred first. CR was defined as disappearance of target and non-target lesions and normalization of tumour markers. Pathological lymph nodes short axis measures \<10 mm. PR was defined as \>=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 was defined as \>=20% increase in sum of diameters of measured lesions taking as references smallest sum of diameters recorded on study(including baseline), absolute increase of \>=5 mm/appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions. |
| Disease Control Rate (DCR) | Up to 33.7 months | DCR was defined as percentage of participants with a best overall response (BOR), extracranial and intracranial response of CR, PR or stable disease (SD). As per RECIST version 1.1 CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures \<10 mm. PR was defined as \>=30% decrease in sum of measures (longest diameter for tumor 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 was defined as \>=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 \>=5 mm absolute increase. Appearance of one or more new lesions was considered progression. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. |
| Percentage Change From Baseline in Tumor Size | Baseline up to 33.7 months | Tumor size was defined as the sum lengths of the longest diameters of the target lesion. Percentage change in tumor size was determined for participants with measurable disease at baseline. Baseline for RECIST version 1.1 was defined as the last evaluable assessment prior to starting treatment. |
| Progression Free Survival (PFS) | Up to 33.7 months | 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 was defined as at least 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. |
| Overall Survival (OS) | Up to 33.7 months | OS was defined as the time from the date of first dose to date of death due to any cause. |
| 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 | Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0 | 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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method. |
Countries
Spain, United Kingdom, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Lazertinib 240 mg Participants with EGFRm+ advanced NSCLC with or without asymptomatic brain metastasis received lazertinib tablet at a dose of 240 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. Participants were then followed up for safety for 28 days after the last dose of study treatment. | 15 |
| Lazertinib 320 mg Participants 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. Participants were then followed up for safety for 28 days after the last dose of study treatment. | 13 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 11 | 9 |
| Overall Study | Enrolled but not-treated | 0 | 1 |
| Overall Study | Participants did not complete the 28 days follow-up after implementation of protocol amendment 11 | 3 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Lazertinib 320 mg | Total | Lazertinib 240 mg |
|---|---|---|---|
| Age, Continuous | 63 years STANDARD_DEVIATION 12.48 | 61.7 years STANDARD_DEVIATION 11.72 | 60.6 years STANDARD_DEVIATION 11.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 25 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Number of prior lines of therapy <= 4 Lines | 4 Participants | 12 Participants | 8 Participants |
| Number of prior lines of therapy > 4 Lines | 9 Participants | 16 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 9 Participants | 20 Participants | 11 Participants |
| Region of Enrollment SPAIN | 8 Participants | 18 Participants | 10 Participants |
| Region of Enrollment UNITED KINGDOM | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment UNITED STATES | 4 Participants | 9 Participants | 5 Participants |
| Sex: Female, Male Female | 8 Participants | 17 Participants | 9 Participants |
| Sex: Female, Male Male | 5 Participants | 11 Participants | 6 Participants |
| Weight group >= 80 kg | 2 Participants | 4 Participants | 2 Participants |
| Weight group < 80 kilograms (kg) | 10 Participants | 23 Participants | 13 Participants |
| Weight group Not Reported | 1 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 15 | 9 / 13 |
| other Total, other adverse events | 15 / 15 | 11 / 13 |
| serious Total, serious adverse events | 10 / 15 | 6 / 13 |
Outcome results
Primary
Part D: Accumulation Ratio (Rac) for Multiple Dose of Lazertinib
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 outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Accumulation Ratio (Rac) for Multiple Dose of Lazertinib | 2.26 Ratio | Standard Deviation 0.61 |
| Lazertinib 320 mg | Part D: Accumulation Ratio (Rac) for Multiple Dose of Lazertinib | 2.36 Ratio | Standard Deviation 1.08 |
Primary
Part D: Apparent Plasma Clearance at Steady State (CLss/F) for Multiple Dose of Lazertinib
CLss/F was defined as apparent plasma clearance at steady state. CLss/F for multiple dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Apparent Plasma Clearance at Steady State (CLss/F) for Multiple Dose of Lazertinib | 44.25 Liters per hour (L/h) | Standard Deviation 21.39 |
| Lazertinib 320 mg | Part D: Apparent Plasma Clearance at Steady State (CLss/F) for Multiple Dose of Lazertinib | 50.10 Liters per hour (L/h) | Standard Deviation 37.21 |
Primary
Part D: Apparent Plasma Clearance (CL/F) for Single Dose of Lazertinib
CL/F was defined as apparent plasma clearance. CL/F for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Apparent Plasma Clearance (CL/F) for Single Dose of Lazertinib | 41.92 Liters per hour (L/h) | Standard Deviation 15.56 |
| Lazertinib 320 mg | Part D: Apparent Plasma Clearance (CL/F) for Single Dose of Lazertinib | 39.38 Liters per hour (L/h) | Standard Deviation 12.96 |
Primary
Part D: Apparent Terminal Elimination Rate Constant (Lambda[z]) for Single Dose of Lazertinib
Lambda(z) was defined as terminal elimination rate constant. Lambda(z) for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Apparent Terminal Elimination Rate Constant (Lambda[z]) for Single Dose of Lazertinib | 0.02 Per hour (1/h) | Standard Deviation 0.01 |
| Lazertinib 320 mg | Part D: Apparent Terminal Elimination Rate Constant (Lambda[z]) for Single Dose of Lazertinib | 0.01 Per hour (1/h) | Standard Deviation 0 |
Primary
Part D: Apparent Terminal Half-Life (t1/2) for Single Dose of Lazertinib
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 outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Apparent Terminal Half-Life (t1/2) for Single Dose of Lazertinib | 51.12 Hours | Full Range 18.75 |
| Lazertinib 320 mg | Part D: Apparent Terminal Half-Life (t1/2) for Single Dose of Lazertinib | 63.98 Hours | Full Range 52.3 |
Primary
Part D: Apparent Volume of Distribution (Vd/F) for Single Dose of Lazertinib
Vd/F was defined as apparent volume of distribution. Vd/F for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Apparent Volume of Distribution (Vd/F) for Single Dose of Lazertinib | 2990.36 Liters | Standard Deviation 1188.45 |
| Lazertinib 320 mg | Part D: Apparent Volume of Distribution (Vd/F) for Single Dose of Lazertinib | 3822.19 Liters | Standard Deviation 984.29 |
Primary
Part D: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC[0-24]) for Single Dose of Lazertinib
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 outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose, 1, 2, 4, 10 and 24 hours post-dose on Day 1 of Cycle 0
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC[0-24]) for Single Dose of Lazertinib | 3253.58 h*ng/mL | Standard Deviation 916.67 |
| Lazertinib 320 mg | Part D: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC[0-24]) for Single Dose of Lazertinib | 4097.34 h*ng/mL | Standard Deviation 1261.96 |
Primary
Part D: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) for Single Dose of Lazertinib
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 outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) for Single Dose of Lazertinib | 6504.88 h*ng/mL | Standard Deviation 2542.12 |
| Lazertinib 320 mg | Part D: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) for Single Dose of Lazertinib | 8869.21 h*ng/mL | Standard Deviation 2642.17 |
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
AUCss(0-last) was defined as area under the plasma concentration time curve from time zero to end of dosing interval at steady state. AUCss(0-last) for multiple dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | 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 | 7025.10 h*ng/mL | Standard Deviation 4181.22 |
| Lazertinib 320 mg | 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 | 9249.58 h*ng/mL | Standard Deviation 4924.51 |
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
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 outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method.
Time frame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
Population: Pharmacokinetic (PK) analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | 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 | 5907.56 Hour*nanograms per milliliter (h*ng/mL) | Standard Deviation 2218.84 |
| Lazertinib 320 mg | 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 | 7664.99 Hour*nanograms per milliliter (h*ng/mL) | Standard Deviation 2057.13 |
Primary
Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Multiple Dose of Lazertinib
Cmax,ss was defined as maximum observed plasma concentration at steady state. Cmax,ss for multiple dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Multiple Dose of Lazertinib | 509.92 ng/mL | Standard Deviation 236.66 |
| Lazertinib 320 mg | Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Multiple Dose of Lazertinib | 632.00 ng/mL | Standard Deviation 279.88 |
Primary
Part D: Maximum Observed Plasma Concentration (Cmax) for Single Dose of Lazertinib
Cmax was defined as maximum observed plasma concentration. Cmax for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Maximum Observed Plasma Concentration (Cmax) for Single Dose of Lazertinib | 441.04 Nanograms per milliliter (ng/mL) | Standard Deviation 135.45 |
| Lazertinib 320 mg | Part D: Maximum Observed Plasma Concentration (Cmax) for Single Dose of Lazertinib | 524.13 Nanograms per milliliter (ng/mL) | Standard Deviation 271.58 |
Primary
Part D: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Tests
Number of participants with clinically significant abnormalities in electrocardiogram (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.
Time frame: From Day 1 up to 14 months
Population: The safety analysis population included all participants who received at least 1 dose of IP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lazertinib 240 mg | Part D: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Tests | 1 Participants |
| Lazertinib 320 mg | Part D: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Tests | 1 Participants |
Primary
Part D: Number of Participants With Clinically Significant Abnormalities in Physical Examination
Number of participants with clinically significant abnormalities in physical examination were 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.
Time frame: From Day 1 up to 14 months
Population: The safety analysis population included all participants who received at least 1 dose of IP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lazertinib 240 mg | Part D: Number of Participants With Clinically Significant Abnormalities in Physical Examination | 8 Participants |
| Lazertinib 320 mg | Part D: Number of Participants With Clinically Significant Abnormalities in Physical Examination | 2 Participants |
Primary
Part D: Number of Participants With Clinically Significant Abnormalities in Vital Signs
Number of participants 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.
Time frame: From Day 1 up to 14 months
Population: The safety analysis population included all participants who received at least 1 dose of IP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lazertinib 240 mg | Part D: Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Lazertinib 320 mg | Part D: Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
Primary
Part D: Number of Participants 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 (v) 4.03
Safety laboratory assessments included clinical chemistry, hematology and urinalysis. Grading was done 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.
Time frame: From Day 1 up to 14 months
Population: The safety analysis population included all participants who received at least 1 dose of IP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lazertinib 240 mg | Part D: Number of Participants 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 (v) 4.03 | 2 Participants |
| Lazertinib 320 mg | Part D: Number of Participants 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 (v) 4.03 | 0 Participants |
Primary
Part D: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a clinical study participant 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 outcome measure.
Time frame: From Day 1 up to 14 months
Population: The safety analysis population included all participants who received at least 1 dose of investigational product (IP).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lazertinib 240 mg | Part D: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 15 Participants |
| Lazertinib 320 mg | Part D: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 13 Participants |
Primary
Part D: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) for Multiple Dose of Lazertinib
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 outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) for Multiple Dose of Lazertinib | 3.15 Hours | Full Range 1.75 |
| Lazertinib 320 mg | Part D: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) for Multiple Dose of Lazertinib | 3.97 Hours | Full Range 2.22 |
Primary
Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Single Dose of Lazertinib
Tmax was defined as time to reach the maximum observed plasma concentration. Tmax for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Single Dose of Lazertinib | 2.00 Hours | Full Range 0.92 |
| Lazertinib 320 mg | Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Single Dose of Lazertinib | 2.50 Hours | Full Range 1.07 |
Primary
Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 1
Ctrough was defined as pre-dose plasma concentration. Ctrough for multiple dose of lazertinib at Cycle 1 Day 1 was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose on Day 1 of Cycle 1
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 1 | 6.41 ng/mL | Standard Deviation 4.55 |
| Lazertinib 320 mg | Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 1 | 10.91 ng/mL | Standard Deviation 5.99 |
Primary
Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 15
Ctrough was defined as pre-dose plasma concentration. Ctrough for multiple dose of lazertinib at Cycle 1 Day 15 was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose on Day 15 of Cycle 1
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 15 | 177.40 ng/mL | Standard Deviation 99.23 |
| Lazertinib 320 mg | Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 15 | 263.74 ng/mL | Standard Deviation 145.61 |
Primary
Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 8
Ctrough was defined as pre-dose plasma concentration. Ctrough for multiple dose of lazertinib at Cycle 1 Day 8 was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose on Day 8 of Cycle 1
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 8 | 154.62 ng/mL | Standard Deviation 87.6 |
| Lazertinib 320 mg | Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 8 | 225.47 ng/mL | Standard Deviation 168.22 |
Secondary
Disease Control Rate (DCR)
DCR was defined as percentage of participants with a best overall response (BOR), extracranial and intracranial response of CR, PR or stable disease (SD). As per RECIST version 1.1 CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures \<10 mm. PR was defined as \>=30% decrease in sum of measures (longest diameter for tumor 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 was defined as \>=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 \>=5 mm absolute increase. Appearance of one or more new lesions was considered progression. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: Up to 33.7 months
Population: Evaluable for response population included all participants in safety analysis population who had a baseline RECIST version 1.1 assessment.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Disease Control Rate (DCR) | 60.0 Percentage of participants | 95% Confidence Interval 35.2 |
| Lazertinib 320 mg | Disease Control Rate (DCR) | 53.8 Percentage of participants | 95% Confidence Interval 26.7 |
Secondary
Duration of Response (DoR)
DOR was defined as time between date of first documented confirmed response (PR/CR) and date of first documented progression or death, whichever occurred first. CR was defined as disappearance of target and non-target lesions and normalization of tumour markers. Pathological lymph nodes short axis measures \<10 mm. PR was defined as \>=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 was defined as \>=20% increase in sum of diameters of measured lesions taking as references smallest sum of diameters recorded on study(including baseline), absolute increase of \>=5 mm/appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions.
Time frame: Up to 33.7 months
Population: Evaluable for response population included all participants in safety analysis population who had a baseline RECIST version 1.1 assessment. Here 'N' (number of participants analyzed) refers to number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lazertinib 240 mg | Duration of Response (DoR) | NA Months |
| Lazertinib 320 mg | Duration of Response (DoR) | 2.8 Months |
Secondary
Objective Response Rate (ORR)
ORR was defined as percentage of participants who had at least 1 confirmed partial or complete response (PR or CR) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 prior to disease progression or recurrence. CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (\<) 10 millimeter (mm). PR was defined as greater than or equal to (\>=) 30 percent (%) decrease in sum of measures (longest diameter for tumor 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 was defined as \>=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 \>=5 mm. Appearance of one or more new lesions was considered progression.
Time frame: Up to 33.7 months
Population: Evaluable for response population included all participants in safety analysis population who had a baseline RECIST version 1.1 assessment.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Objective Response Rate (ORR) | 26.7 Percentage of participants | 95% Confidence Interval 4.3 |
| Lazertinib 320 mg | Objective Response Rate (ORR) | 7.7 Percentage of participants | 95% Confidence Interval 0 |
Secondary
Overall Survival (OS)
OS was defined as the time from the date of first dose to date of death due to any cause.
Time frame: Up to 33.7 months
Population: The safety analysis population included all participants who received at least 1 dose of IP. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Overall Survival (OS) | 9.1 Months | Full Range 2.6 |
| Lazertinib 320 mg | Overall Survival (OS) | 7.7 Months | Full Range 3.4 |
Secondary
Part D: Accumulation Ratio (Rac) of Metabolite M7 After Multiple Dose of Lazertinib
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. Rac of metabolite M7 after multiple dose of lazertinib was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Accumulation Ratio (Rac) of Metabolite M7 After Multiple Dose of Lazertinib | 1.976 Ratio | Standard Deviation 0.617 |
| Lazertinib 320 mg | Part D: Accumulation Ratio (Rac) of Metabolite M7 After Multiple Dose of Lazertinib | 2.270 Ratio | Standard Deviation 1.3 |
Secondary
Part D: Apparent Terminal Elimination Rate Constant (Lambda [z]) of Metabolite M7 After Single Dose of Lazertinib
Lambda(z) was defined as terminal elimination rate constant. Lambda(z) of metabolite M7 after single dose of lazertinib was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Apparent Terminal Elimination Rate Constant (Lambda [z]) of Metabolite M7 After Single Dose of Lazertinib | 0.017 Per hour (1/h) | Standard Deviation 0.008 |
| Lazertinib 320 mg | Part D: Apparent Terminal Elimination Rate Constant (Lambda [z]) of Metabolite M7 After Single Dose of Lazertinib | 0.021 Per hour (1/h) | Standard Deviation 0.016 |
Secondary
Part D: Apparent Terminal Half-Life (t1/2) of Metabolite M7 After Single Dose of Lazertinib
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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Apparent Terminal Half-Life (t1/2) of Metabolite M7 After Single Dose of Lazertinib | 41.205 Hours | Full Range 18.042 |
| Lazertinib 320 mg | Part D: Apparent Terminal Half-Life (t1/2) of Metabolite M7 After Single Dose of Lazertinib | 50.019 Hours | Full Range 13.256 |
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
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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose, 1, 2, 4, 10 and 24 hours post-dose on Day 1 of Cycle 0
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | 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 | 86.692 h*ng/mL | Standard Deviation 52.492 |
| Lazertinib 320 mg | 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 | 74.523 h*ng/mL | Standard Deviation 33.137 |
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
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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | 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 | 281.172 h*ng/mL | Standard Deviation 144.163 |
| Lazertinib 320 mg | 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 | 263.373 h*ng/mL | Standard Deviation 166.254 |
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
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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | 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 | 148.335 h*ng/mL | Standard Deviation 89.794 |
| Lazertinib 320 mg | 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 | 168.765 h*ng/mL | Standard Deviation 159.476 |
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
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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | 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 | 216.350 h*ng/mL | Standard Deviation 126.357 |
| Lazertinib 320 mg | 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 | 208.908 h*ng/mL | Standard Deviation 128.968 |
Secondary
Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib
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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib | 7.866 ng/mL | Standard Deviation 4.213 |
| Lazertinib 320 mg | Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib | 8.319 ng/mL | Standard Deviation 7.418 |
Secondary
Part D: Maximum Observed Plasma Concentration (Cmax) of Metabolite M7 After Single Dose of Lazertinib
Cmax was defined as maximum observed plasma concentration. Cmax of metabolite M7 after single dose of lazertinib was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Maximum Observed Plasma Concentration (Cmax) of Metabolite M7 After Single Dose of Lazertinib | 5.838 ng/mL | Standard Deviation 3.946 |
| Lazertinib 320 mg | Part D: Maximum Observed Plasma Concentration (Cmax) of Metabolite M7 After Single Dose of Lazertinib | 4.774 ng/mL | Standard Deviation 2.257 |
Secondary
Part D: Metabolic Ratio at Steady State (MRss) of Metabolite M7 and Lazertinib After Multiple Dose of Lazertinib
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. The concentrations of metabolite M7 and lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Metabolic Ratio at Steady State (MRss) of Metabolite M7 and Lazertinib After Multiple Dose of Lazertinib | 0.021 Ratio | Standard Deviation 0.006 |
| Lazertinib 320 mg | Part D: Metabolic Ratio at Steady State (MRss) of Metabolite M7 and Lazertinib After Multiple Dose of Lazertinib | 0.016 Ratio | Standard Deviation 0.009 |
Secondary
Part D: Metabolic Ratio (MR) of Metabolite M7 and Lazertinib After Single Dose of Lazertinib
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. The concentrations of metabolite M7 and lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Metabolic Ratio (MR) of Metabolite M7 and Lazertinib After Single Dose of Lazertinib | 0.042 Ratio | Standard Deviation 0.022 |
| Lazertinib 320 mg | Part D: Metabolic Ratio (MR) of Metabolite M7 and Lazertinib After Single Dose of Lazertinib | 0.027 Ratio | Standard Deviation 0.015 |
Secondary
Part D: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib
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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib | 6.330 Hours | Full Range 2.25 |
| Lazertinib 320 mg | Part D: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib | 4.350 Hours | Full Range 3.93 |
Secondary
Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolite M7 After Single Dose of Lazertinib
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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolite M7 After Single Dose of Lazertinib | 4.020 Hours | Full Range 2.07 |
| Lazertinib 320 mg | Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolite M7 After Single Dose of Lazertinib | 4.150 Hours | Full Range 3.08 |
Secondary
Part D: Trough Concentrations (Ctrough) of Metabolite M7 After Multiple Dose of Lazertinib at Days 1, 8 and 15 of Cycle 1
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 outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Time frame: Pre-dose on Days 1, 8 and 15 of Cycle 1
Population: PK analysis population included all participants who had at least 1 measurable concentration collected post dose. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure. Here 'n' (number analyzed) refers to all participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lazertinib 240 mg | Part D: Trough Concentrations (Ctrough) of Metabolite M7 After Multiple Dose of Lazertinib at Days 1, 8 and 15 of Cycle 1 | Day 1 Cycle 1 | 0.257 ng/mL | Standard Deviation 0.237 |
| Lazertinib 240 mg | Part D: Trough Concentrations (Ctrough) of Metabolite M7 After Multiple Dose of Lazertinib at Days 1, 8 and 15 of Cycle 1 | Day 8 Cycle 1 | 4.928 ng/mL | Standard Deviation 3.005 |
| Lazertinib 240 mg | Part D: Trough Concentrations (Ctrough) of Metabolite M7 After Multiple Dose of Lazertinib at Days 1, 8 and 15 of Cycle 1 | Day 15 Cycle 1 | 5.356 ng/mL | Standard Deviation 3.604 |
| Lazertinib 320 mg | Part D: Trough Concentrations (Ctrough) of Metabolite M7 After Multiple Dose of Lazertinib at Days 1, 8 and 15 of Cycle 1 | Day 1 Cycle 1 | 0.358 ng/mL | Standard Deviation 0.321 |
| Lazertinib 320 mg | Part D: Trough Concentrations (Ctrough) of Metabolite M7 After Multiple Dose of Lazertinib at Days 1, 8 and 15 of Cycle 1 | Day 8 Cycle 1 | 5.791 ng/mL | Standard Deviation 4.65 |
| Lazertinib 320 mg | Part D: Trough Concentrations (Ctrough) of Metabolite M7 After Multiple Dose of Lazertinib at Days 1, 8 and 15 of Cycle 1 | Day 15 Cycle 1 | 6.340 ng/mL | Standard Deviation 4.741 |
Secondary
Percentage Change From Baseline in Tumor Size
Tumor size was defined as the sum lengths of the longest diameters of the target lesion. Percentage change in tumor size was determined for participants with measurable disease at baseline. Baseline for RECIST version 1.1 was defined as the last evaluable assessment prior to starting treatment.
Time frame: Baseline up to 33.7 months
Population: Evaluable for response population included all participants in safety analysis population who had a baseline RECIST version 1.1 assessment. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Percentage Change From Baseline in Tumor Size | -5.37 Percentage change in tumor size | Standard Deviation 37.68 |
| Lazertinib 320 mg | Percentage Change From Baseline in Tumor Size | 9.56 Percentage change in tumor size | Standard Deviation 42.89 |
Secondary
Progression Free Survival (PFS)
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 was defined as at least 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.
Time frame: Up to 33.7 months
Population: The safety analysis population included all participants who received at least 1 dose of IP. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Lazertinib 240 mg | Progression Free Survival (PFS) | 3.1 Months | Full Range 1.3 |
| Lazertinib 320 mg | Progression Free Survival (PFS) | 4.2 Months | Full Range 0 |