Clinical Trial of YH25448(Lazertinib) as the First-line Treatment in Patients With EGFR Mutation Positive Locally Advanced or Metastatic NSCLC (LASER301)
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Drug: Gefitinib 250 mgDrug: Lazertinib 240 mg/160 mgDrug: Lazertinib-matching placebo 240 mg/160 mgDrug: Gefitinib-matching placebo 250 mg
- Registration Number
- NCT04248829
- Lead Sponsor
- Yuhan Corporation
- 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
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 393
- 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
-
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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Gefitinib + Lazertinib-matching placebo Gefitinib 250 mg Gefitinib (250 mg orally, once daily) plus Lazertinib-matching placebo (240 mg or 160 mg orally, once daily) in accordance with the randomization schedule Gefitinib + Lazertinib-matching placebo Lazertinib-matching placebo 240 mg/160 mg Gefitinib (250 mg orally, once daily) plus Lazertinib-matching placebo (240 mg or 160 mg orally, once daily) in accordance with the randomization schedule Lazertinib + Gefitinib-matching placebo Lazertinib 240 mg/160 mg Lazertinib (240 mg or 160 mg orally, once daily) plus Gefitinib-matching placebo (250 mg orally, once daily) in accordance with the randomization schedule Lazertinib + Gefitinib-matching placebo Gefitinib-matching placebo 250 mg Lazertinib (240 mg or 160 mg orally, once daily) plus Gefitinib-matching placebo (250 mg orally, once daily) in accordance with the randomization schedule
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) According to RECIST v1.1 by Investigator Assessment 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. 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).
- Secondary Outcome Measures
Name Time Method Disease Control Rate (DCR) According to RECIST v1.1 by Investigator Assessments 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. 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.
Change From Baseline in Euro-Quality of Life-5 Dimension-5 Level (EQ-5D-5L) 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). 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 to Response According to RECIST v1.1 by Investigator Assessments At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression. 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.
Cerebrospinal Fluid (CSF) Concentrations of Lazertinib A cerebrospinal fluid (CSF) sample once collected from participants with brain metastases, at Cycle 5 Day 1 or afterward. To characterize the pharmacokinetics (PK) of lazertinib.
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 Items (QLQ-C30) 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). 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 / problemsDepth of Response According to RECIST v1.1 by Investigator Assessments At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression. 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.
Overall Survival (OS) 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.) 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.
Plasma Concentrations of Lazertinib 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. To characterize the pharmacokinetics (PK) of lazertinib.
Objective Response Rate (ORR) According to RECIST v1.1 by Investigator Assessments 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. 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.
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Lung Cancer 13 Items (EORTC QLQ-LC13) 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). 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.Duration of Response (DoR) According to RECIST v1.1 by Investigator Assessments 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. 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.
Trial Locations
- Locations (80)
Perpetual Succour Hospital
🇵🇭Cebu, Philippines
Prince of Songkla University
🇹🇭Hat Yai, Thailand
Tsentralna miska klinichna likarnia
🇺🇦Úzhgorod, Zakarpats'ka Oblast', Ukraine
Komunalne nekomertsiine pidpryiemstvo Sumskoi oblasnoi rady "Sumskyi klinichnyi onkolohichnyi tsentr", onkotorakalne viddilennia, Sumskyi derzhavnyi universytet, kafedra onkolohii ta radiolohii, m. Sumy
🇺🇦Sumy, Ukraine
Hospital Tengku Ampuan Afzan
🇲🇾Kuantan, Pahang, Malaysia
Arkhangelsk Regional Clinical Oncological Dispensary
🇷🇺Arkhangel'sk, Arkhangel'skaya Oblast', Russian Federation
LLC "Eurocityclinic"
🇷🇺Saint Petersburg, Russian Federation
Chiang Mai University - Faculty of Medicine
🇹🇭Chiang Mai, Thailand
VitaMed LLC
🇷🇺Moscow, Russian Federation
Budgetary Healthcare Institution of Omsk Region "Clinical Oncology Dispensary"
🇷🇺Omsk, Russian Federation
Theageneio Anticancer Hospital of Thessaloniki
🇬🇷Thessaloníki, Greece
Attikon Hospital
🇬🇷Athens, Greece
Debreceni Egyetem
🇭🇺Debrecen, Hungary
National Cancer Center
🇰🇷Goyang-si, Gyeonggi-do, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Gyeongsang National University Hospital
🇰🇷Jinju-si, Gyeongsangnam-do, Korea, Republic of
Ajou University Hospital
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
Yeungnam University Medical Center
🇰🇷Daegu, Korea, Republic of
Kangbuk Samsung Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
SMG-SNU Boramae Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Sultan Ismail
🇲🇾Johor Bahru, Johor, Malaysia
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Selangor, Malaysia
Hospital Umum Sarawak
🇲🇾Kuching, Sarawak, Malaysia
Philippine General Hospital
🇵🇭Manila, Philippines
GBUZ of Nizhny Novgorod region Clinical diagnostic center
🇷🇺Nizhny Novgorod, Nizhegorodskaya Oblast', Russian Federation
Republic Clinical Oncology Despensary
🇷🇺Kazan, Russian Federation
MBUZ City Clinical Hospital #1
🇷🇺Novosibirsk, Russian Federation
Medincentre (GLAVUPDK)
🇷🇺Moscow, Russian Federation
First St. Petersburg State Medical University n. a. Pavlov
🇷🇺Saint Petersburg, Russian Federation
GBUZ "Regional clinical oncologic dispensary of Volgograd"
🇷🇺Volgograd, Russian Federation
Institute for Pulmonary Diseases of Vojvodina
🇷🇸Sremska Kamenica, Vojvodina, Serbia
Yaroslavl regional oncology hospital
🇷🇺Yaroslavl, Russian Federation
Clinical Hospital Center "Bezanijska Kosa"
🇷🇸Belgrade, Serbia
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Ramathibodi Hospital, Mahidol University
🇹🇭Bangkok, Thailand
Siriraj Hospital
🇹🇭Bangkok, Thailand
Adana Baskent Practice and Research Hospital
🇹🇷Adana, Turkey
Srinagarind Hospital, Khon Kaen University
🇹🇭Khon Kaen, Thailand
Cukurova University Medical Faculty
🇹🇷Adana, Turkey
Medical Point İzmir Hospital
🇹🇷İzmir, Turkey
Komunalne nekomertsiine pidpryiemstvo Kharkivskoi oblasnoi rady "Oblasnyi klinichnyi spetsializovanyi dyspanser radiatsiinoho zakhystu naselennia" - khirurhichne viddilennia
🇺🇦Kharkiv, Kharkivs'ka Oblast', Ukraine
Hacettepe University Medical Faculty - Medical Oncology
🇹🇷Ankara, Turkey
Istanbul Medeniyet University Goztepe Training and Research Hospital - Medical Oncology
🇹🇷Istanbul, Turkey
Ankara Liv Hospital
🇹🇷Ankara, Turkey
Trakya University Medical Faculty
🇹🇷Edirne, Turkey
Inonu University Turgut Ozal Medical Center
🇹🇷Malatya, Turkey
Kocaeli University Medical Faculty
🇹🇷Kocaeli, Turkey
Kyiv City Clinical Oncology Center - Department of Chemotherapy
🇺🇦Kyiv, Ukraine
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Eugenideio Therapeutirio - Ongcology Department
🇬🇷Athens, Greece
Törökbálinti Tüdőgyógyintézet
🇭🇺Törökbálint, Hungary
Chungbuk National University Hospital
🇰🇷Cheongju-si, Chungcheongbuk-do, Korea, Republic of
The Catholic University of Korea, Bucheon St. Mary's Hospital
🇰🇷Bucheon-si, Gyeonggi-do, Korea, Republic of
CHA Bundang Medical Center, CHA University
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
The Catholic University of Korea, St. Vincent's Hospital
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
Inje University Haeundae Paik Hospital
🇰🇷Busan, Korea, Republic of
Keimyung University Dongsan Medical Center
🇰🇷Daegu, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, Eunpyeong St.Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Raja Perempuan Zainab Ii
🇲🇾Kota Bahru, Kelantan, Malaysia
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
Hospital Pulau Pinang
🇲🇾George Town, Pulau Pinang, Malaysia
Manila Doctors Hospital - Clinical Trial Office
🇵🇭Manila, Quezon, Philippines
GAUZ Republican clinical oncology dispensary of the Ministry
🇷🇺Kazan, Russian Federation
Limited Liability Company "AV Medical Group" - Oncology
🇷🇺Saint Petersburg, Russian Federation
Private medical institution "Euromedservice"
🇷🇺Pushkin, Russian Federation
Saint-Petersburg City Clinical Oncology Dispensary
🇷🇺Saint Petersburg, Russian Federation
Clinical Center Kragujevac
🇷🇸Kragujevac, Serbia
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
National University Hospital
🇸🇬Singapore, Singapore
Oblasne komunalne nekomertsiine pidpryiemstvo "Bukovynskyi klinichnyi onkolohichnyi tsentr", strukturnyi pidrozdil klinichnoi onkolohii, m.Chernivtsi
🇺🇦Chernivtsi, Ukraine
Komunalne nekomertsiine pidpryiemstvo "Miska klinichna likarnia №4" Dniprovskoi miskoi rady", khimioterapevtychne viddilennia z dennym statsionarom, Derzhavnyi zaklad "Dnipropetrovskyi derzhavnyi medychnyi universitet", kafedra onkolohii i medychnoi radio
🇺🇦Dnipro, Ukraine
Podilskyi rehionalnyi tsentr onkolohii, viddilennia khimioterapii
🇺🇦Vinnytsia, Ukraine
Medychnyi tsentr Tovarystva z obmezhenoiu vidpovidalnistiu "Onkolaif"
🇺🇦Zaporizhzhia, Ukraine
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
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