A Study of Lazertinib in Participants With Epidermal Growth Factor Receptor (EGFR) Mutation Positive Advanced Non-Small Cell Lung Cancer (NSCLC)

NCT04075396 | Completed Phase 1 Results FDA Drug

• 4 other identifiers: CR10868073841937NSC2001YH25448-2012019-003106-28
• Study Type: interventional
• Target: 29
• Locations: 3 countries
• Sites: 9

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).

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (22)

• 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.

  From Day 1 up to 14 months

• 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.

  From Day 1 up to 14 months

• 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.

  From Day 1 up to 14 months

• 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.

  From Day 1 up to 14 months

• 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.

  From Day 1 up to 14 months

• 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.

  Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0

• 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.

  Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0

• 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.

  Pre-dose, 1, 2, 4, 10 and 24 hours post-dose on Day 1 of Cycle 0

• 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.

  Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0

• 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.

  Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0

• 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.

  Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0

• 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.

  Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0

• 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.

  Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0

• 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.

  Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0

• 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.

  Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2

• 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.

  Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2

• 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.

  Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2

• 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.

  Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2

• 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.

  Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2

• 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.

  Pre-dose on Day 1 of Cycle 1

• 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.

  Pre-dose on Day 8 of Cycle 1

• 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.

  Pre-dose on Day 15 of Cycle 1

Secondary Outcomes (20)

• 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

• 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

• 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

• 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

• 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

Study Arms (1)

Part D: Outside of Korea

EXPERIMENTAL

Participants from outside of Korea with progressive disease and on prior epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKI) therapy will receive recommended phase 2 doses based on safety, tolerability, efficacy and pharmacokinetics (PK) of Lazertinib.

Drug: Lazertinib

Interventions

Lazertinib DRUG

Participants will receive Lazertinib tablets once daily.

Also known as: YH25448, JNJ-73841937

Part D: Outside of Korea

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead
• Yuhan Corporation: collaborator

Study Sites (9)

City of Hope

Duarte, California, 91010, United States

Location

Advent Health Orlando

Orlando, Florida, 32804, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37211, United States

Location

Hosp Univ Vall D Hebron

Barcelona, 8035, Spain

Location

Hosp. Gral. Univ. Gregorio Maranon

Madrid, 28009, Spain

Location

Hosp Virgen de La Victoria

Málaga, 29010, Spain

Location

The Christie Nhs Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

• Kim B, Lee J, Jang H, Lee N, Mehta J, Jang SB. Effects of Acid-Reducing Agents on the Pharmacokinetics of Lazertinib in Patients with EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer. Adv Ther. 2022 Oct;39(10):4757-4771. doi: 10.1007/s12325-022-02286-z. Epub 2022 Aug 13.

  PMID: 35962934 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

lazertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Executive Medical Director Oncology
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2019
• First Posted: August 30, 2019
• Study Start: October 16, 2019
• Primary Completion: January 8, 2021
• Study Completion: November 14, 2022
• Last Updated: April 29, 2025
• Results First Posted: February 28, 2024

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

ES (3); US (5); GB (1)