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
YH25448 is an oral, highly potent, mutant-selective and irreversible EGFR Tyrosine-kinase inhibitors (TKIs) that targets both the T790M mutation and activating EGFR mutations while sparing wild type EGFR. This is a Phase III, Randomized, Double-blind study evaluating the efficacy and safety of YH25448 (240 mg orally, once daily) versus Gefitinib (250 mg orally, once daily) in patients with locally advanced or metastatic NSCLC that is known to be EGFR sensitizing mutation (EGFRm) positive, treatment-naïve and eligible for first-line treatment with an EGFR-TKI.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
393
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
The initial dose for Gefitinib (250 mg once daily) cannot be reduced to a lower dose
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
Progression-Free Survival (PFS) According to RECIST v1.1 by Investigator Assessment
PFS was defined as the time from randomization until the date of objective progression or death(by any cause whichever comes first based on investigator assessment using RECIST v1.1 and was used to assess the efficacy of lazertinib compared to the gefitinib).
Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression, assessed up to 29 months per participant.
Objective Response Rate (ORR) According to RECIST v1.1 by Investigator Assessments
ORR was defined as the percentage of participants with measurable disease with at least on visit response of complete response(CR) or Partial response(PR) and it was used to further assess the efficacy of lazertinib compared with gefitinib.
Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression, assessed up to 29 months per participant.
Duration of Response (DoR) According to RECIST v1.1 by Investigator Assessments
DoR was defined as the time from the date of first documented response(CR or PR) until the date of documented progression or death, whichever comes first and was used to further assess the efficacy of lazertinib compared with gefitinib.
Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression, assessed up to 29 months per participant.
Disease Control Rate (DCR) According to RECIST v1.1 by Investigator Assessments
DCR was defined as the percentage of participants who have a best overall response of CR or PR or SD(SD at \>= 6weeks prior to any PD event) and was used to further assess the efficacy of lazertinib compared with gefitinib.
Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression, assessed up to 29 months per participant.
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The initial dose for Gefitinib-matching placebo (250 mg once daily) cannot be reduced to a lower dose
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
Eugenideio Therapeutirio - Ongcology Department
Athens, Greece
Attikon Hospital
Athens, Greece
Theageneio Anticancer Hospital of Thessaloniki
Thessaloniki, Greece
Debreceni Egyetem
Debrecen, Hungary
Törökbálinti Tüdőgyógyintézet
Törökbálint, Hungary
Hospital Sultan Ismail
Johor Bahru, Johor, Malaysia
Hospital Raja Perempuan Zainab Ii
Kota Bharu, Kelantan, Malaysia
Hospital Tengku Ampuan Afzan
Kuantan, Pahang, Malaysia
Hospital Pulau Pinang
George Town, Pulau Pinang, Malaysia
...and 70 more locations
Depth of Response According to RECIST v1.1 by Investigator Assessments
The depth of response was defined as the best percent change in the sum of diameters of target lesions in the absense of new lesions or progression of non-target lesions compared to the baseline and was used to further assess the efficacy of lazertinib compared with gefitinib.
Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression.
Time to Response According to RECIST v1.1 by Investigator Assessments
Time to Response was defined as the time from the date of randomization until the date of first documented response and was used to further assess the efficacy of lazertinib compared with gefitinib.
Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression.
Overall Survival (OS)
OS was defined as the time from the date of randomization until the date of death due to any cause and was used to further assess the efficacy of lazertinib compared with gefitinib.
Time frame: From the randomization to end of study or date of death from any cause, whichever comes first, assessed every 6 weeks. (Up to 29 months per participant.)
Plasma Concentrations of Lazertinib
To characterize the pharmacokinetics (PK) of lazertinib.
Time frame: Blood samples collected from each participant at pre-dose, 1 to 3 hours, and 4 to 6 hours post-dose on Day 1 Cycle 1, Day 1 Cycle 2, Day 1 Cycle 5, Day 1 Cycle 9, and Day 1 Cycle 13.
Cerebrospinal Fluid (CSF) Concentrations of Lazertinib
To characterize the pharmacokinetics (PK) of lazertinib.
Time frame: A cerebrospinal fluid (CSF) sample once collected from participants with brain metastases, at Cycle 5 Day 1 or afterward.
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 participants' 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 participants (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
Time frame: Questionnaires completed at Cycle 1 Day1 , Cycle2 Day 1 and then every 6 weeks relative to the randomization date until 28d safety f/u or progression f/u visit(whichever is later).
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.
Time frame: Questionnaires completed at Cycle 1 Day1 , Cycle2 Day 1 and then every 6 weeks relative to the randomization date until 28d safety f/u or progression f/u visit(whichever is later).
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 participants 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.
Time frame: Questionnaires completed at Cycle 1 Day1 , Cycle2 Day 1 and then every 6 weeks relative to the randomization date until 28d safety f/u or progression f/u visit(whichever is later).