Clinical trial NCT04075396: A Study of Lazertinib in Participants With Epidermal Growth Factor Receptor (EGFR) Mutation Positive Advanced Non-Small Cell Lung Cancer (NSCLC)
Official title: A Phase I/II, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of YH25448 in Patients With EGFR Mutation Positive Advanced Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: Yuhan Corporation
First posted: 2019-08-30
Enrollment: 29
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Part D: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From Day 1 up to 14 months
measure: Part D: Number of Participants With Clinically Significant Abnormalities in Vital Signs
timeFrame: From Day 1 up to 14 months
measure: Part D: Number of Participants With Clinically Significant Abnormalities in Physical Examination
timeFrame: From Day 1 up to 14 months
measure: 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
timeFrame: From Day 1 up to 14 months
measure: Part D: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Tests
timeFrame: From Day 1 up to 14 months
measure: 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
timeFrame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
measure: Part D: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) for Single Dose of Lazertinib
timeFrame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
measure: Part D: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC[0-24]) for Single Dose of Lazertinib
timeFrame: Pre-dose, 1, 2, 4, 10 and 24 hours post-dose on Day 1 of Cycle 0
measure: Part D: Maximum Observed Plasma Concentration (Cmax) for Single Dose of Lazertinib
timeFrame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
measure: Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Single Dose of Lazertinib
timeFrame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
measure: Part D: Apparent Terminal Half-Life (t1/2) for Single Dose of Lazertinib
timeFrame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
measure: Part D: Apparent Terminal Elimination Rate Constant (Lambda[z]) for Single Dose of Lazertinib
timeFrame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
measure: Part D: Apparent Plasma Clearance (CL/F) for Single Dose of Lazertinib
timeFrame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
measure: Part D: Apparent Volume of Distribution (Vd/F) for Single Dose of Lazertinib
timeFrame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
measure: 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
timeFrame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
measure: Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Multiple Dose of Lazertinib
timeFrame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
measure: Part D: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) for Multiple Dose of Lazertinib
timeFrame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
measure: Part D: Accumulation Ratio (Rac) for Multiple Dose of Lazertinib
timeFrame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
measure: Part D: Apparent Plasma Clearance at Steady State (CLss/F) for Multiple Dose of Lazertinib
timeFrame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
measure: Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 1
timeFrame: Pre-dose on Day 1 of Cycle 1
measure: Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 8
timeFrame: Pre-dose on Day 8 of Cycle 1
measure: Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 15
timeFrame: Pre-dose on Day 15 of Cycle 1
Secondary outcomes:
measure: 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
timeFrame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
measure: 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
timeFrame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
measure: 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
timeFrame: Pre-dose, 1, 2, 4, 10 and 24 hours post-dose on Day 1 of Cycle 0
measure: Part D: Maximum Observed Plasma Concentration (Cmax) of Metabolite M7 After Single Dose of Lazertinib
timeFrame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
measure: Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolite M7 After Single Dose of Lazertinib
timeFrame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
measure: Part D: Apparent Terminal Half-Life (t1/2) of Metabolite M7 After Single Dose of Lazertinib
timeFrame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
measure: Part D: Apparent Terminal Elimination Rate Constant (Lambda [z]) of Metabolite M7 After Single Dose of Lazertinib
timeFrame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
measure: Part D: Metabolic Ratio (MR) of Metabolite M7 and Lazertinib After Single Dose of Lazertinib
timeFrame: Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0
measure: 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
timeFrame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
measure: Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib
timeFrame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
measure: Part D: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib
timeFrame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
measure: Part D: Accumulation Ratio (Rac) of Metabolite M7 After Multiple Dose of Lazertinib
timeFrame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
measure: Part D: Trough Concentrations (Ctrough) of Metabolite M7 After Multiple Dose of Lazertinib at Days 1, 8 and 15 of Cycle 1
timeFrame: Pre-dose on Days 1, 8 and 15 of Cycle 1
measure: Part D: Metabolic Ratio at Steady State (MRss) of Metabolite M7 and Lazertinib After Multiple Dose of Lazertinib
timeFrame: Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2
measure: Objective Response Rate (ORR)
timeFrame: Up to 33.7 months
measure: Duration of Response (DoR)
timeFrame: Up to 33.7 months
measure: Disease Control Rate (DCR)
timeFrame: Up to 33.7 months
measure: Percentage Change From Baseline in Tumor Size
timeFrame: Baseline up to 33.7 months
measure: Progression Free Survival (PFS)
timeFrame: Up to 33.7 months
measure: Overall Survival (OS)
timeFrame: Up to 33.7 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Orlando
country: United States
facility: Advent Health Orlando
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Maranon
city: Malaga
country: Spain
facility: Hosp Virgen de La Victoria
city: Manchester
country: United Kingdom
facility: The Christie Nhs Foundation Trust
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.