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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04248829




Registration number
NCT04248829
Ethics application status
Date submitted
14/01/2020
Date registered
30/01/2020
Date last updated
3/05/2021

Titles & IDs
Public title
Clinical Trial of YH25448(Lazertinib) as the First-line Treatment in Patients With EGFR Mutation Positive Locally Advanced or Metastatic NSCLC (LASER301)
Scientific title
A Phase III, Randomized, Double-blind Study to Assess the Efficacy and Safety of Lazertinib Versus Gefitinib as the First-line Treatment in Patients With Epidermal Growth Factor Receptor Sensitizing Mutation Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Secondary ID [1] 0 0
YH25448-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lazertinib 240 mg/160 mg
Treatment: Drugs - Gefitinib 250 mg
Treatment: Drugs - Lazertinib-matching placebo 240 mg/160 mg
Treatment: Drugs - Gefitinib-matching placebo 250 mg

Experimental: Lazertinib + Gefitinib-matching placebo - Lazertinib (240 mg or 160 mg orally, once daily) plus Gefitinib-matching placebo (250 mg orally, once daily) in accordance with the randomization schedule

Active Comparator: Gefitinib + Lazertinib-matching placebo - Gefitinib (250 mg orally, once daily) plus Lazertinib-matching placebo (240 mg or 160 mg orally, once daily) in accordance with the randomization schedule


Treatment: Drugs: Lazertinib 240 mg/160 mg
The initial dose of lazertinib 240 mg (3 tablets of 80 mg lazertinib) once daily can be reduced to 160 mg once daily (2 tablets of 80 mg lazertinib) under specific circumstances

Treatment: Drugs: Gefitinib 250 mg
The initial dose for Gefitinib (250 mg once daily) cannot be reduced to a lower dose

Treatment: Drugs: Lazertinib-matching placebo 240 mg/160 mg
The initial dose of lazertinib-matching placebo 240 mg (3 tablets of 80 mg lazertinib-matching placebo) once daily can be reduced to 160 mg once daily (2 tablets of 80 mg lazertinib-matching placebo) under specific circumstances

Treatment: Drugs: Gefitinib-matching placebo 250 mg
The initial dose for Gefitinib-matching placebo (250 mg once daily) cannot be reduced to a lower dose

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS) according to RECIST v1.1 by Investigator assessment - To assess the efficacy of lazertinib compared with gefitinib as measured by PFS
Timepoint [1] 0 0
The primary analysis of PFS based on investigator assessment will occur when PFS maturity is observed at approximately 27 months after the first patient is randomized
Secondary outcome [1] 0 0
Objective Response Rate (ORR) according to RECIST v1.1 by Investigator assessments - To further assess the efficacy of lazertinib compared with gefitinib
Timepoint [1] 0 0
ORR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized
Secondary outcome [2] 0 0
Duration of Response (DoR) according to RECIST v1.1 by Investigator assessments - To further assess the efficacy of lazertinib compared with gefitinib
Timepoint [2] 0 0
DoR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized
Secondary outcome [3] 0 0
Disease Control Rate (DCR) according to RECIST v1.1 by Investigator assessments - To further assess the efficacy of lazertinib compared with gefitinib
Timepoint [3] 0 0
DCR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized
Secondary outcome [4] 0 0
Depth of Response according to RECIST v1.1 by Investigator assessments - To further assess the efficacy of lazertinib compared with gefitinib
Timepoint [4] 0 0
Depth of Response analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized
Secondary outcome [5] 0 0
Time to Response according to RECIST v1.1 by Investigator assessments - To further assess the efficacy of lazertinib compared with gefitinib
Timepoint [5] 0 0
Time to Response analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized
Secondary outcome [6] 0 0
Overall survival (OS) - To assess OS of lazertinib compared with gefitinib
Timepoint [6] 0 0
OS will be analyzed at 2 time points: when PFS maturity is observed at approximately 27 months after the first patient is randomized, and when OS maturity is observed at approximately 45 months after the first patient is randomized
Secondary outcome [7] 0 0
Plasma concentrations of lazertinib - To characterize the pharmacokinetics (PK) of lazertinib
Timepoint [7] 0 0
Plasma concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized
Secondary outcome [8] 0 0
Plasma concentrations of Metabolite YH26334 - To characterize the PK of lazertinib metabolite YH26334
Timepoint [8] 0 0
Plasma concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized
Secondary outcome [9] 0 0
Ratio of YH26334 to lazertinib plasma concentration - To characterize the PK of lazertinib and YH26334
Timepoint [9] 0 0
Ratio of YH26334 to lazertinib plasma concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized
Secondary outcome [10] 0 0
Cerebrospinal fluid (CSF) concentrations of lazertinib - To characterize the PK of lazertinib
Timepoint [10] 0 0
CSF concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized
Secondary outcome [11] 0 0
CSF concentrations of Metabolite YH26334 - To characterize the PK of lazertinib metabolite YH26334
Timepoint [11] 0 0
CSF concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized
Secondary outcome [12] 0 0
Ratio of CSF to plasma concentration of lazertinib and YH26334 - To characterize the PK of lazertinib and YH26334
Timepoint [12] 0 0
Ratio of CSF to plasma concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized
Secondary outcome [13] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 items (QLQ-C30) - The EORTC QLQ-C30 consists of 30 items and measures cancer patients' functioning (health related quality of life (HRQoL)) and symptoms for all cancer types. Questions can be grouped into 5 multi item functional scales (physical, role, emotional, cognitive, and social); 3 multi item symptom scales (fatigue, pain, nausea/vomiting); a 2 item global HRQoL scale; 5 single items assessing additional symptoms commonly reported by cancer patients (dyspnea, loss of appetite, insomnia, constipation, diarrhea) and 1 item on the financial impact of the disease.
All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
a high score for a functional scale represents a high / healthy level of functioning
a high score for the global health status / QoL represents a high QoL
but a high score for a symptom scale / item represents a high level of symptomatology / problems
Timepoint [13] 0 0
EORTC-QLQ-C30 analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized
Secondary outcome [14] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Lung Cancer 13 items (EORTC QLQ-LC13) - The EORTC QLQ-LC13 includes questions assessing cough, hemoptysis, dyspnea, site specific pain (symptoms), sore mouth, dysphagia, peripheral neuropathy, and alopecia (treatment related side effects), and pain medication.
The items on both measures were scaled and scored using the recommended EORTC procedures. Raw scores were transformed to a linear scale ranging from 0 to 100, with a higher score representing a higher level of functioning or higher level of symptoms. Provided at least half of the items in the scale were completed, the scale score was calculated using only those items for which values existed.
Timepoint [14] 0 0
EORTC QLQ-LC13 analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized
Secondary outcome [15] 0 0
Change From Baseline in Euro-Quality of Life-5 Dimension-5 level (EQ-5D-5L) - The EQ-5D comprises the following two questionnaires:
The EQ-5D comprises 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension comprises five levels (no problems, slight problems, moderate problem, severe problem, unable/extreme problems).
The EQ VAS records the patients self-rated health status on a vertical graduated (0-100) visual analogue scale. The patient's self-rated health is assessed on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) by the EQ-VAS.
Timepoint [15] 0 0
EQ-5D-5L analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized

Eligibility
Key inclusion criteria
- Pathologically confirmed adenocarcinoma of the lung

- Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy

- At least 1 of the 2 common EGFR mutations known to be associated with EGFR TKI
sensitivity (Ex19del or L858R), either alone or in combination with other EGFR
mutations

- Treatment-naïve for locally advanced or metastatic NSCLC

- WHO performance status score of 0 to 1 with no clinically significant deterioration
over the previous 2 weeks before randomization

- At least 1 measurable lesion, not previously irradiated and not chosen for biopsy
during the study Screening period
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Symptomatic and unstable brain metastases

- Leptomeningeal metastases

- Symptomatic spinal cord compression

- History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis
which required steroid treatment, or any evidence of clinically active ILD

- Any medical conditions requiring chronic continuous oxygen therapy

- History of any malignancy other than the disease under study within 3 years before
randomization

- Any cardiovascular disease as follows:

- History of symptomatic chronic heart failure or serious cardiac arrhythmia
requiring active treatment

- History of myocardial infarction or unstable angina within 24 weeks of
randomization

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Calvary Mater Newcastle - Newcastle
Recruitment hospital [2] 0 0
The Townsville Hospital - Douglas
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [4] 0 0
Peninsula & South Eastern Haematology and Oncology Group - Frankston
Recruitment postcode(s) [1] 0 0
2298 - Newcastle
Recruitment postcode(s) [2] 0 0
4814 - Douglas
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
3199 - Frankston
Recruitment outside Australia
Country [1] 0 0
Greece
State/province [1] 0 0
Athens
Country [2] 0 0
Greece
State/province [2] 0 0
Larissa
Country [3] 0 0
Greece
State/province [3] 0 0
Patras
Country [4] 0 0
Greece
State/province [4] 0 0
Thessaloníki
Country [5] 0 0
Hungary
State/province [5] 0 0
Budapest
Country [6] 0 0
Hungary
State/province [6] 0 0
Debrecen
Country [7] 0 0
Hungary
State/province [7] 0 0
Székesfehérvár
Country [8] 0 0
Hungary
State/province [8] 0 0
Tatabánya
Country [9] 0 0
Hungary
State/province [9] 0 0
Törökbálint
Country [10] 0 0
Korea, Republic of
State/province [10] 0 0
Chungcheongbuk-do
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Gangwon-do
Country [12] 0 0
Korea, Republic of
State/province [12] 0 0
Gyeonggi-do
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Gyeongsangnam-do
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Busan
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Daegu
Country [16] 0 0
Korea, Republic of
State/province [16] 0 0
Incheon
Country [17] 0 0
Korea, Republic of
State/province [17] 0 0
Seoul
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Ulsan
Country [19] 0 0
Malaysia
State/province [19] 0 0
Johor
Country [20] 0 0
Malaysia
State/province [20] 0 0
Kelantan
Country [21] 0 0
Malaysia
State/province [21] 0 0
Pahang
Country [22] 0 0
Malaysia
State/province [22] 0 0
Pulau Pinang
Country [23] 0 0
Malaysia
State/province [23] 0 0
Sarawak
Country [24] 0 0
Malaysia
State/province [24] 0 0
Selangor
Country [25] 0 0
Philippines
State/province [25] 0 0
Quezon
Country [26] 0 0
Philippines
State/province [26] 0 0
Bacolod City
Country [27] 0 0
Philippines
State/province [27] 0 0
Cebu
Country [28] 0 0
Philippines
State/province [28] 0 0
Manila
Country [29] 0 0
Philippines
State/province [29] 0 0
Quezon City
Country [30] 0 0
Russian Federation
State/province [30] 0 0
Arkhangel'skaya Oblast'
Country [31] 0 0
Russian Federation
State/province [31] 0 0
Kursk Oblast
Country [32] 0 0
Russian Federation
State/province [32] 0 0
Nizhegorodskaya Oblast'
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Stavropol'skiy Kray
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Kazan
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Moscow
Country [36] 0 0
Russian Federation
State/province [36] 0 0
Novosibirsk
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Omsk
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Pushkin
Country [39] 0 0
Russian Federation
State/province [39] 0 0
Saint Petersburg
Country [40] 0 0
Russian Federation
State/province [40] 0 0
Tomsk
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Volgograd
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Yaroslavl
Country [43] 0 0
Serbia
State/province [43] 0 0
Vojvodina
Country [44] 0 0
Serbia
State/province [44] 0 0
Belgrade
Country [45] 0 0
Serbia
State/province [45] 0 0
Kragujevac
Country [46] 0 0
Serbia
State/province [46] 0 0
Niš
Country [47] 0 0
Singapore
State/province [47] 0 0
Singapore
Country [48] 0 0
Taiwan
State/province [48] 0 0
Kaohsiung
Country [49] 0 0
Taiwan
State/province [49] 0 0
Taichung
Country [50] 0 0
Taiwan
State/province [50] 0 0
Tainan
Country [51] 0 0
Taiwan
State/province [51] 0 0
Taipei
Country [52] 0 0
Taiwan
State/province [52] 0 0
Taoyuan
Country [53] 0 0
Thailand
State/province [53] 0 0
Bangkok
Country [54] 0 0
Thailand
State/province [54] 0 0
Chiang Mai
Country [55] 0 0
Thailand
State/province [55] 0 0
Hat Yai
Country [56] 0 0
Thailand
State/province [56] 0 0
Khon Kaen
Country [57] 0 0
Turkey
State/province [57] 0 0
Adana
Country [58] 0 0
Turkey
State/province [58] 0 0
Ankara
Country [59] 0 0
Turkey
State/province [59] 0 0
Edirne
Country [60] 0 0
Turkey
State/province [60] 0 0
Istanbul
Country [61] 0 0
Turkey
State/province [61] 0 0
Izmir
Country [62] 0 0
Turkey
State/province [62] 0 0
Kocaeli
Country [63] 0 0
Turkey
State/province [63] 0 0
Konya
Country [64] 0 0
Turkey
State/province [64] 0 0
Malatya
Country [65] 0 0
Ukraine
State/province [65] 0 0
Kharkivs'ka Oblast'
Country [66] 0 0
Ukraine
State/province [66] 0 0
Volyns'ka Oblast'
Country [67] 0 0
Ukraine
State/province [67] 0 0
Zakarpats'ka Oblast'
Country [68] 0 0
Ukraine
State/province [68] 0 0
Chernivtsi
Country [69] 0 0
Ukraine
State/province [69] 0 0
Dnipro
Country [70] 0 0
Ukraine
State/province [70] 0 0
Kharkiv
Country [71] 0 0
Ukraine
State/province [71] 0 0
Kyiv
Country [72] 0 0
Ukraine
State/province [72] 0 0
Sumy
Country [73] 0 0
Ukraine
State/province [73] 0 0
Uzhhorod
Country [74] 0 0
Ukraine
State/province [74] 0 0
Vinnytsia
Country [75] 0 0
Ukraine
State/province [75] 0 0
Zaporizhzhia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Yuhan Corporation
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This Phase III study will be conducted to evaluate the efficacy and safety of YH25448 as
first-line treatment in locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC)
patients with EGFR mutations
Trial website
https://clinicaltrials.gov/show/NCT04248829
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Dongmin Kim
Address 0 0
Country 0 0
Phone 0 0
+82-2-828-0523
Fax 0 0
Email 0 0
kdm27@yuhan.co.kr
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04248829