Clinical Trial of YH25448(Lazertinib) as the First-line Treatment in Patients With EGFR Mutation Positive Locally Advanced or Metastatic NSCLC (LASER301)

Non-Small Cell Lung Cancer Clinical Trial

Official 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04248829
• Other study ID #: YH25448-301
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 13, 2020
• Est. completion date: June 2024

Study information

• Verified date: April 2024
• Source: Yuhan Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 393
• Est. completion date: June 2024
• Est. primary completion date: July 29, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

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

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Greece	Attikon Hospital	Athens
Greece	Eugenideio Therapeutirio - Ongcology Department	Athens
Greece	Theageneio Anticancer Hospital of Thessaloniki	Thessaloníki
Hungary	Debreceni Egyetem	Debrecen
Hungary	Törökbálinti Tüdogyógyintézet	Törökbálint
Korea, Republic of	The Catholic University of Korea, Bucheon St. Mary's Hospital	Bucheon-si	Gyeonggi-do
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si	Chungcheongbuk-do
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Yeungnam University Medical Center	Daegu
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Gyeongsang National University Hospital	Jinju-si	Gyeongsangnam-do
Korea, Republic of	CHA Bundang Medical Center, CHA University	Seongnam-si	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	SMG-SNU Boramae Medical Center	Seoul
Korea, Republic of	The Catholic University of Korea, Eunpyeong St.Mary's Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon-si	Gyeonggi-do
Korea, Republic of	The Catholic University of Korea, St. Vincent's Hospital	Suwon-si	Gyeonggi-do
Korea, Republic of	Ulsan University Hospital	Ulsan
Malaysia	Hospital Pulau Pinang	George Town	Pulau Pinang
Malaysia	Hospital Sultan Ismail	Johor Bahru	Johor
Malaysia	Hospital Raja Perempuan Zainab Ii	Kota Bahru	Kelantan
Malaysia	University Malaya Medical Centre	Kuala Lumpur	Selangor
Malaysia	Hospital Tengku Ampuan Afzan	Kuantan	Pahang
Malaysia	Hospital Umum Sarawak	Kuching	Sarawak
Philippines	Perpetual Succour Hospital	Cebu
Philippines	Manila Doctors Hospital - Clinical Trial Office	Manila	Quezon
Philippines	Philippine General Hospital	Manila
Russian Federation	Arkhangelsk Regional Clinical Oncological Dispensary	Arkhangel'sk	Arkhangel'skaya Oblast'
Russian Federation	GAUZ Republican clinical oncology dispensary of the Ministry	Kazan
Russian Federation	Republic Clinical Oncology Despensary	Kazan
Russian Federation	Medincentre (GLAVUPDK)	Moscow
Russian Federation	VitaMed LLC	Moscow
Russian Federation	GBUZ of Nizhny Novgorod region Clinical diagnostic center	Nizhny Novgorod	Nizhegorodskaya Oblast'
Russian Federation	MBUZ City Clinical Hospital #1	Novosibirsk
Russian Federation	Budgetary Healthcare Institution of Omsk Region "Clinical Oncology Dispensary"	Omsk
Russian Federation	Private medical institution "Euromedservice"	Pushkin
Russian Federation	First St. Petersburg State Medical University n. a. Pavlov	Saint Petersburg
Russian Federation	Limited Liability Company "AV Medical Group" - Oncology	Saint Petersburg
Russian Federation	LLC "Eurocityclinic"	Saint Petersburg
Russian Federation	Saint-Petersburg City Clinical Oncology Dispensary	Saint Petersburg
Russian Federation	GBUZ "Regional clinical oncologic dispensary of Volgograd"	Volgograd
Russian Federation	Yaroslavl regional oncology hospital	Yaroslavl
Serbia	Clinical Hospital Center "Bezanijska Kosa"	Belgrade
Serbia	Clinical Center Kragujevac	Kragujevac
Serbia	Institute for Pulmonary Diseases of Vojvodina	Sremska Kamenica	Vojvodina
Singapore	National University Hospital	Singapore
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Thailand	Ramathibodi Hospital, Mahidol University	Bangkok
Thailand	Siriraj Hospital	Bangkok
Thailand	Chiang Mai University - Faculty of Medicine	Chiang Mai
Thailand	Prince of Songkla University	Hat Yai
Thailand	Srinagarind Hospital, Khon Kaen University	Khon Kaen
Turkey	Adana Baskent Practice and Research Hospital	Adana
Turkey	Cukurova University Medical Faculty	Adana
Turkey	Ankara Liv Hospital	Ankara
Turkey	Hacettepe University Medical Faculty - Medical Oncology	Ankara
Turkey	Trakya University Medical Faculty	Edirne
Turkey	Istanbul Medeniyet University Goztepe Training and Research Hospital - Medical Oncology	Istanbul
Turkey	Medical Point Izmir Hospital	Izmir
Turkey	Kocaeli University Medical Faculty	Kocaeli
Turkey	Inonu University Turgut Ozal Medical Center	Malatya
Ukraine	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	Komunalne nekomertsiine pidpryiemstvo Kharkivskoi oblasnoi rady "Oblasnyi klinichnyi spetsializovanyi dyspanser radiatsiinoho zakhystu naselennia" - khirurhichne viddilennia	Kharkiv	Kharkivs'ka Oblast'
Ukraine	Kyiv City Clinical Oncology Center - Department of Chemotherapy	Kyiv
Ukraine	Komunalne nekomertsiine pidpryiemstvo Sumskoi oblasnoi rady "Sumskyi klinichnyi onkolohichnyi tsentr", onkotorakalne viddilennia, Sumskyi derzhavnyi universytet, kafedra onkolohii ta radiolohii, m. Sumy	Sumy
Ukraine	Tsentralna miska klinichna likarnia	Úzhgorod	Zakarpats'ka Oblast'
Ukraine	Podilskyi rehionalnyi tsentr onkolohii, viddilennia khimioterapii	Vinnytsia
Ukraine	Medychnyi tsentr Tovarystva z obmezhenoiu vidpovidalnistiu "Onkolaif"	Zaporizhzhia

Sponsors (1)

Lead Sponsor	Collaborator
Yuhan Corporation

Countries where clinical trial is conducted

Australia,  Greece,  Hungary,  Korea, Republic of,  Malaysia,  Philippines,  Russian Federation,  Serbia,  Singapore,  Taiwan,  Thailand,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	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.
Secondary	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.	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.
Secondary	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.	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.
Secondary	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.	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.
Secondary	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.	At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression.
Secondary	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.	At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression.
Secondary	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.	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.)
Secondary	Plasma Concentrations of Lazertinib	To characterize the pharmacokinetics (PK) 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.
Secondary	Cerebrospinal Fluid (CSF) Concentrations of Lazertinib	To characterize the pharmacokinetics (PK) of lazertinib.	A cerebrospinal fluid (CSF) sample once collected from participants with brain metastases, at Cycle 5 Day 1 or afterward.
Secondary	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	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).
Secondary	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.	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).
Secondary	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.	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).