Clinical trial NCT04248829: Clinical Trial of YH25448(Lazertinib) as the First-line Treatment in Patients With EGFR Mutation Positive Locally Advanced or Metastatic NSCLC (LASER301)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
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
Lead sponsor: Yuhan Corporation
Sponsor class: INDUSTRY
First posted: 2020-01-30
Enrollment: 393
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-Free Survival (PFS) According to RECIST v1.1 by Investigator Assessment
timeFrame: 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:
measure: Objective Response Rate (ORR) According to RECIST v1.1 by Investigator Assessments
timeFrame: 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.
measure: Duration of Response (DoR) According to RECIST v1.1 by Investigator Assessments
timeFrame: 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.
measure: Disease Control Rate (DCR) According to RECIST v1.1 by Investigator Assessments
timeFrame: 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.
measure: Depth of Response According to RECIST v1.1 by Investigator Assessments
timeFrame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression.
measure: Time to Response According to RECIST v1.1 by Investigator Assessments
timeFrame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression.
measure: Overall Survival (OS)
timeFrame: 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.)
measure: Plasma Concentrations of Lazertinib
timeFrame: 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.
measure: Cerebrospinal Fluid (CSF) Concentrations of Lazertinib
timeFrame: A cerebrospinal fluid (CSF) sample once collected from participants with brain metastases, at Cycle 5 Day 1 or afterward.
measure: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 Items (QLQ-C30)
timeFrame: 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).
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Lung Cancer 13 Items (EORTC QLQ-LC13)
timeFrame: 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).
measure: Change From Baseline in Euro-Quality of Life-5 Dimension-5 Level (EQ-5D-5L)
timeFrame: 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).
Other outcomes:
Locations:
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Athens
country: Greece
facility: Eugenideio Therapeutirio - Ongcology Department
city: Athens
country: Greece
facility: Attikon Hospital
city: Thessaloníki
country: Greece
facility: Theageneio Anticancer Hospital of Thessaloniki
city: Debrecen
country: Hungary
facility: Debreceni Egyetem
city: Törökbálint
country: Hungary
facility: Törökbálinti Tüdőgyógyintézet
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
state: Chungcheongbuk-do
city: Bucheon-si
country: Korea, Republic of
facility: The Catholic University of Korea, Bucheon St. Mary's Hospital
state: Gyeonggi-do
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: CHA Bundang Medical Center, CHA University
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent's Hospital
state: Gyeonggi-do
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital
state: Gyeonggi-do
city: Jinju-si
country: Korea, Republic of
facility: Gyeongsang National University Hospital
state: Gyeongsangnam-do
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Medical Center
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Eunpyeong St.Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: SMG-SNU Boramae Medical Center
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Johor Bahru
country: Malaysia
facility: Hospital Sultan Ismail
state: Johor
city: Kota Bahru
country: Malaysia
facility: Hospital Raja Perempuan Zainab Ii
state: Kelantan
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan
state: Pahang
city: George Town
country: Malaysia
facility: Hospital Pulau Pinang
state: Pulau Pinang
city: Kuching
country: Malaysia
facility: Hospital Umum Sarawak
state: Sarawak
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
state: Selangor
city: Manila
country: Philippines
facility: Manila Doctors Hospital - Clinical Trial Office
state: Quezon
city: Cebu
country: Philippines
facility: Perpetual Succour Hospital
city: Manila
country: Philippines
facility: Philippine General Hospital
city: Arkhangel'sk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Oncological Dispensary
state: Arkhangel'skaya Oblast'
city: Nizhny Novgorod
country: Russian Federation
facility: GBUZ of Nizhny Novgorod region Clinical diagnostic center
state: Nizhegorodskaya Oblast'
city: Kazan
country: Russian Federation
facility: GAUZ Republican clinical oncology dispensary of the Ministry
city: Kazan
country: Russian Federation
facility: Republic Clinical Oncology Despensary
city: Moscow
country: Russian Federation
facility: Medincentre (GLAVUPDK)
city: Moscow
country: Russian Federation
facility: VitaMed LLC
city: Novosibirsk
country: Russian Federation
facility: MBUZ City Clinical Hospital #1
city: Omsk
country: Russian Federation
facility: Budgetary Healthcare Institution of Omsk Region "Clinical Oncology Dispensary"
city: Pushkin
country: Russian Federation
facility: Private medical institution "Euromedservice"
city: Saint Petersburg
country: Russian Federation
facility: First St. Petersburg State Medical University n. a. Pavlov
city: Saint Petersburg
country: Russian Federation
facility: LLC "Eurocityclinic"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "AV Medical Group" - Oncology
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg City Clinical Oncology Dispensary
city: Volgograd
country: Russian Federation
facility: GBUZ "Regional clinical oncologic dispensary of Volgograd"
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl regional oncology hospital
city: Sremska Kamenica
country: Serbia
facility: Institute for Pulmonary Diseases of Vojvodina
state: Vojvodina
city: Belgrade
country: Serbia
facility: Clinical Hospital Center "Bezanijska Kosa"
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
city: Singapore
country: Singapore
facility: National University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital, Mahidol University
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Chiang Mai
country: Thailand
facility: Chiang Mai University - Faculty of Medicine
city: Hat Yai
country: Thailand
facility: Prince of Songkla University
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital, Khon Kaen University
city: Adana
country: Turkey
facility: Adana Baskent Practice and Research Hospital
city: Adana
country: Turkey
facility: Cukurova University Medical Faculty
city: Ankara
country: Turkey
facility: Ankara Liv Hospital
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty - Medical Oncology
city: Edirne
country: Turkey
facility: Trakya University Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul Medeniyet University Goztepe Training and Research Hospital - Medical Oncology
city: İzmir
country: Turkey
facility: Medical Point İzmir Hospital
city: Kocaeli
country: Turkey
facility: Kocaeli University Medical Faculty
city: Malatya
country: Turkey
facility: Inonu University Turgut Ozal Medical Center
city: Kharkiv
country: Ukraine
facility: Komunalne nekomertsiine pidpryiemstvo Kharkivskoi oblasnoi rady "Oblasnyi klinichnyi spetsializovanyi dyspanser radiatsiinoho zakhystu naselennia" - khirurhichne viddilennia
state: Kharkivs'ka Oblast'
city: Úzhgorod
country: Ukraine
facility: Tsentralna miska klinichna likarnia
state: Zakarpats'ka Oblast'
city: Chernivtsi
country: Ukraine
facility: Oblasne komunalne nekomertsiine pidpryiemstvo "Bukovynskyi klinichnyi onkolohichnyi tsentr", strukturnyi pidrozdil klinichnoi onkolohii, m.Chernivtsi
city: Dnipro
country: Ukraine
facility: 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
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Oncology Center - Department of Chemotherapy
city: Sumy
country: Ukraine
facility: Komunalne nekomertsiine pidpryiemstvo Sumskoi oblasnoi rady "Sumskyi klinichnyi onkolohichnyi tsentr", onkotorakalne viddilennia, Sumskyi derzhavnyi universytet, kafedra onkolohii ta radiolohii, m. Sumy
city: Vinnytsia
country: Ukraine
facility: Podilskyi rehionalnyi tsentr onkolohii, viddilennia khimioterapii
city: Zaporizhzhia
country: Ukraine
facility: Medychnyi tsentr Tovarystva z obmezhenoiu vidpovidalnistiu "Onkolaif"
Study officials:
References: