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

NCT04248829 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 1 other identifier: YH25448-301
• Study Type: interventional
• Target: 393
• Locations: 13 countries
• Sites: 80

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

Conditions

Non-Small Cell Lung Cancer

Keywords

Locally Advanced EGFR Sensitizing Mutation; Metastatic EGFR Sensitizing Mutation; EGFR TKI; Ex19del; L858R; First-line; YH25448; Advanced Non-Small Cell Lung Cancer; Adenocarcinoma of lung; Non-squamous carcinoma of lung; Phase III; Lazertinib

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• 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.

• 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.

• 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.

• Depth 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.

• 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.

Study Arms (2)

Lazertinib + Gefitinib-matching placebo

EXPERIMENTAL

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

Drug: Lazertinib 240 mg/160 mg; Drug: Gefitinib-matching placebo 250 mg

Gefitinib + Lazertinib-matching placebo

ACTIVE COMPARATOR

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

Drug: Gefitinib 250 mg; Drug: Lazertinib-matching placebo 240 mg/160 mg

Interventions

Lazertinib 240 mg/160 mg DRUG

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

Also known as: YH25448 240 mg/160 mg

Lazertinib + Gefitinib-matching placebo

Gefitinib 250 mg DRUG

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

Also known as: Iressa 250 mg

Gefitinib + Lazertinib-matching placebo

Lazertinib-matching placebo 240 mg/160 mg DRUG

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

Also known as: YH25448-matching placebo 240 mg/160 mg

Gefitinib + Lazertinib-matching placebo

Gefitinib-matching placebo 250 mg DRUG

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

Also known as: Iressa-matching placebo 250 mg

Lazertinib + Gefitinib-matching placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yuhan Corporation: lead

Study Sites (80)

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Eugenideio Therapeutirio - Ongcology Department

Athens, 11528, Greece

Location

Attikon Hospital

Athens, 12462, Greece

Location

Theageneio Anticancer Hospital of Thessaloniki

Thessaloniki, 54007, Greece

Location

Debreceni Egyetem

Debrecen, H-4012, Hungary

Location

Törökbálinti Tüdőgyógyintézet

Törökbálint, 2045, Hungary

Location

Hospital Sultan Ismail

Johor Bahru, Johor, 81100, Malaysia

Location

Hospital Raja Perempuan Zainab Ii

Kota Bharu, Kelantan, 15586, Malaysia

Location

Hospital Tengku Ampuan Afzan

Kuantan, Pahang, 25100, Malaysia

Location

Hospital Pulau Pinang

George Town, Pulau Pinang, 10400, Malaysia

Location

Hospital Umum Sarawak

Kuching, Sarawak, 10450, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, Selangor, 59100, Malaysia

Location

Manila Doctors Hospital - Clinical Trial Office

Manila, Quezon, 1000, Philippines

Location

Perpetual Succour Hospital

Cebu, 6000, Philippines

Location

Philippine General Hospital

Manila, 1000, Philippines

Location

Arkhangelsk Regional Clinical Oncological Dispensary

Arkhangelsk, Arkhangelskaya oblast, 163045, Russia

Location

GBUZ of Nizhny Novgorod region Clinical diagnostic center

Nizhny Novgorod, Nizhny Novgorod Oblast, 603006, Russia

Location

GAUZ Republican clinical oncology dispensary of the Ministry

Kazan', 420029, Russia

Location

Republic Clinical Oncology Despensary

Kazan', 420029, Russia

Location

Medincentre (GLAVUPDK)

Moscow, 119034, Russia

Location

VitaMed LLC

Moscow, 121309, Russia

Location

MBUZ City Clinical Hospital #1

Novosibirsk, Russia

Location

Budgetary Healthcare Institution of Omsk Region "Clinical Oncology Dispensary"

Omsk, 644013, Russia

Location

Private medical institution "Euromedservice"

Pushkin, 196603, Russia

Location

First St. Petersburg State Medical University n. a. Pavlov

Saint Petersburg, 197022, Russia

Location

LLC "Eurocityclinic"

Saint Petersburg, 197022, Russia

Location

Limited Liability Company "AV Medical Group" - Oncology

Saint Petersburg, 197082, Russia

Location

Saint-Petersburg City Clinical Oncology Dispensary

Saint Petersburg, 198255, Russia

Location

GBUZ "Regional clinical oncologic dispensary of Volgograd"

Volgograd, 400138, Russia

Location

Yaroslavl regional oncology hospital

Yaroslavl, 150054, Russia

Location

Institute for Pulmonary Diseases of Vojvodina

Kamenitz, Vojvodina, 21204, Serbia

Location

Clinical Hospital Center "Bezanijska Kosa"

Belgrade, 11080, Serbia

Location

Clinical Center Kragujevac

Kragujevac, 34000, Serbia

Location

National University Hospital

Singapore, 119074, Singapore

Location

The Catholic University of Korea, Bucheon St. Mary's Hospital

Bucheon-si, Gyeonggi-do, 14647, South Korea

Location

National Cancer Center

Goyang-si, Gyeonggi-do, 10408, South Korea

Location

CHA Bundang Medical Center, CHA University

Seongnam-si, Gyeonggi-do, 13496, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

The Catholic University of Korea, St. Vincent's Hospital

Suwon, Gyeonggi-do, 16247, South Korea

Location

Ajou University Hospital

Suwon, Gyeonggi-do, 16499, South Korea

Location

Gyeongsang National University Hospital

Jinju, Gyeongsangnam-do, 52727, South Korea

Location

Chungbuk National University Hospital

Cheongju-si, North Chungcheong, 28644, South Korea

Location

Inje University Haeundae Paik Hospital

Busan, 48108, South Korea

Location

Yeungnam University Medical Center

Daegu, 42415, South Korea

Location

Keimyung University Dongsan Medical Center

Daegu, 42601, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Kangbuk Samsung Hospital

Seoul, 03181, South Korea

Location

The Catholic University of Korea, Eunpyeong St.Mary's Hospital

Seoul, 03312, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

Location

SMG-SNU Boramae Medical Center

Seoul, 07061, South Korea

Location

Ulsan University Hospital

Ulsan, 44033, South Korea

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Ramathibodi Hospital, Mahidol University

Bangkok, 10400, Thailand

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Chiang Mai University - Faculty of Medicine

Chiang Mai, 50200, Thailand

Location

Prince of Songkla University

Hat Yai, 90110, Thailand

Location

Srinagarind Hospital, Khon Kaen University

Khon Kaen, 40002, Thailand

Location

Adana Baskent Practice and Research Hospital

Adana, 1120, Turkey (Türkiye)

Location

Cukurova University Medical Faculty

Adana, 1330, Turkey (Türkiye)

Location

Ankara Liv Hospital

Ankara, 06680, Turkey (Türkiye)

Location

Hacettepe University Medical Faculty - Medical Oncology

Ankara, 6230, Turkey (Türkiye)

Location

Trakya University Medical Faculty

Edirne, 22030, Turkey (Türkiye)

Location

Istanbul Medeniyet University Goztepe Training and Research Hospital - Medical Oncology

Istanbul, 34722, Turkey (Türkiye)

Location

Medical Point İzmir Hospital

Izmir, 35560, Turkey (Türkiye)

Location

Kocaeli University Medical Faculty

Kocaeli, 41380, Turkey (Türkiye)

Location

Inonu University Turgut Ozal Medical Center

Malatya, 44280, Turkey (Türkiye)

Location

Komunalne nekomertsiine pidpryiemstvo Kharkivskoi oblasnoi rady "Oblasnyi klinichnyi spetsializovanyi dyspanser radiatsiinoho zakhystu naselennia" - khirurhichne viddilennia

Kharkiv, Kharkivs’ka Oblast’, 61166, Ukraine

Location

Tsentralna miska klinichna likarnia

Uzhhorod, Zakarpattia Oblast, 88000, Ukraine

Location

Oblasne komunalne nekomertsiine pidpryiemstvo "Bukovynskyi klinichnyi onkolohichnyi tsentr", strukturnyi pidrozdil klinichnoi onkolohii, m.Chernivtsi

Chernivtsi, 58013, Ukraine

Location

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, 49102, Ukraine

Location

Kyiv City Clinical Oncology Center - Department of Chemotherapy

Kyiv, 3115, Ukraine

Location

Komunalne nekomertsiine pidpryiemstvo Sumskoi oblasnoi rady "Sumskyi klinichnyi onkolohichnyi tsentr", onkotorakalne viddilennia, Sumskyi derzhavnyi universytet, kafedra onkolohii ta radiolohii, m. Sumy

Sumy, 40022, Ukraine

Location

Podilskyi rehionalnyi tsentr onkolohii, viddilennia khimioterapii

Vinnytsia, 21029, Ukraine

Location

Medychnyi tsentr Tovarystva z obmezhenoiu vidpovidalnistiu "Onkolaif"

Zaporizhzhia, 69059, Ukraine

Location

Related Publications (2)

• Soo RA, Cho BC, Kim JH, Ahn MJ, Lee KH, Zimina A, Orlov S, Bondarenko I, Lee YG, Lim YN, Lee SS, Lee KH, Pang YK, Fong CH, Kang JH, Lim CS, Danchaivijitr P, Kilickap S, Yang JC, Arslan C, Lee H, Park SN, Cicin I. Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset Analysis. J Thorac Oncol. 2023 Dec;18(12):1756-1766. doi: 10.1016/j.jtho.2023.08.017. Epub 2023 Oct 22.

  PMID: 37865896 DERIVED

• Cho BC, Ahn MJ, Kang JH, Soo RA, Reungwetwattana T, Yang JC, Cicin I, Kim DW, Wu YL, Lu S, Lee KH, Pang YK, Zimina A, Fong CH, Poddubskaya E, Sezer A, How SH, Danchaivijitr P, Kim Y, Lim Y, An T, Lee H, Byun HM, Zaric B. Lazertinib Versus Gefitinib as First-Line Treatment in Patients With EGFR-Mutated Advanced Non-Small-Cell Lung Cancer: Results From LASER301. J Clin Oncol. 2023 Sep 10;41(26):4208-4217. doi: 10.1200/JCO.23.00515. Epub 2023 Jun 28.

  PMID: 37379502 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung

Interventions

lazertinib; Gefitinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dongmin Kim
• Organization: Yuhan Corporation

clinicaltrials@yuhan.co.kr

+82-2-828-0523

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Approximately 380 patients will be randomized in a 1:1 ratio to either lazertinib (n=190) or gefitinib (n= 190). Following objective disease progression according to RECIST v1.1, as per investigator assessment, patients who were randomized to gefitinib arm may have the option to receive open-label lazertinib

Study Record Dates

• First Submitted: January 14, 2020
• First Posted: January 30, 2020
• Study Start: February 13, 2020
• Primary Completion: July 29, 2022
• Study Completion (Estimated): June 1, 2026
• Last Updated: December 3, 2024
• Results First Posted: March 22, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 1 year and ending 5 years after all trial primary and secondary endpoints were assessed.
• Access Criteria: Only requests from researchers who provide a methodologically sound proposal will be reviewed and approved by the sponsor. The analysis type should be in accordance with aims in the proposal approved by the sponsor. Proposals should be directed to hmbyun@yuhan.co.kr.

Locations

SE (3); HU (2); KR (22); TU (9); TH (5); UA (8); TW (2); RU (15); MY (6); AU (1); PH (3); SG (1); GR (3)