A study to test the efficacy and safety of Lazertinib in the treatment of patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer

2024-514771-18-00 Protocol YH25448-301 Therapeutic confirmatory (Phase III) Ended

Start 15 Dec 2020 · End 22 Apr 2026 · Status Ended · 2 EU/EEA countries · 4 sites · Protocol YH25448-301

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ended
Participants planned 71
Countries 2
Sites 4

Adenocarcinoma of the lung (non-small cell lung cancer); locally advanced or metastatic, not amenable to curative surgery or radiotherapy

To assess the efficacy of lazertinib compared with gefitinib as measured by progression-free survival

Key facts

Sponsor
Yuhan Corp.
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Neoplasms [C04]
Trial duration
15 Dec 2020 → 22 Apr 2026
Decision date (initial)
2024-11-13
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
Yuhan Corporation

External identifiers

EU CT number
2024-514771-18-00
EudraCT number
2019-004814-32
ClinicalTrials.gov
NCT04248829

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenetic, Safety, Pharmacokinetic, Pharmacoeconomic

To assess the efficacy of lazertinib compared with gefitinib as measured by progression-free survival

Secondary objectives 4

  1. To further assess the efficacy of lazertinib compared with gefitinib
  2. To assess overall survival of lazertinib compared with gefitinib
  3. To characterize the pharmacokinetics of lazertinib
  4. To assess the impact of lazertinib compared with gefitinib on patient's disease-related symptoms and Health Related Quality of Life

Conditions and MedDRA coding

Adenocarcinoma of the lung (non-small cell lung cancer); locally advanced or metastatic, not amenable to curative surgery or radiotherapy

VersionLevelCodeTermSystem organ class
27.0 PT 10059515 Non-small cell lung cancer metastatic 100000004864
21.0 LLT 10001164 Adenocarcinoma lung stage III 10029104
21.0 LLT 10001165 Adenocarcinoma lung stage IV 10029104

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. Pathologically confirmed adenocarcinoma of the lung
  2. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy
  3. 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
  4. Treatment-naïve for locally advanced or metastatic NSCLC
  5. WHO performance status score of 0 to 1 with no clinically significant deterioration over the previous 2 weeks before randomization
  6. At least 1 measurable lesion, not previously irradiated and not chosen for biopsy during the study Screening period

Exclusion criteria 7

  1. Symptomatic and unstable brain metastases
  2. Leptomeningeal metastases
  3. Symptomatic spinal cord compression
  4. History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
  5. Any medical conditions requiring chronic continuous oxygen therapy
  6. History of any malignancy other than the disease under study within 3 years before randomization
  7. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Progression-free survival according to RECIST v1.1 by Investigator assessment

Secondary endpoints 4

  1. • Objective Response Rate (ORR) • Duration of Response (DoR) • Disease Control Rate (DCR) • Depth of Response • Time to Response All according to RECIST v1.1 by Investigator assessments
  2. Overall survival (OS)
  3. • Plasma concentrations of lazertinib • Cerebrospinal fluid (CSF) concentrations of lazertinib
  4. Change from baseline in : • European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 items (EORTC QLQ-C30) • European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Lung Cancer 13 items (EORTC QLQ-LC13) • Euro-Quality of Life-5 Dimension-5 level (EQ-5D-5L)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Lazertinib

PRD8032964 · Product

Active substance
Lazertinib
Pharmaceutical form
TABLET
Route of administration
ORAL USE
Max daily dose
240 mg milligram(s)
Max total dose
512.4 g gram(s)
Max treatment duration
70 Month(s)
Authorisation status
Not Authorised
MA holder
YUHAN CORPORATION
Paediatric formulation
No
Orphan designation
No

Comparator 1

Gefitinib-ratiopharm 250 mg Filmtabletten

PRD7229804 · Product

Active substance
Gefitinib
Substance synonyms
ZD-1839, N-(3-CHLORO-4-FLUOROPHENYL)-7-METHOXY-6-(3-4-MORPHOLIN)PROPOXY)-4-QUINAZOLINAMINE
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Max daily dose
250 mg milligram(s)
Max total dose
533.75 g gram(s)
Max treatment duration
70 Month(s)
Authorisation status
Authorised
ATC code
L01EB01 — -
Marketing authorisation
2200163.00.00
MA holder
RATIOPHARM GMBH
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Relabeling of the inner and outer package according to EU-CTR requirements

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Yuhan Corp.

2 Total trials 1 Recruiting 1 Ended
Commercial
Sponsor organisation
Yuhan Corp.
Address
Dongjak Gu, 74 Noryangjin Ro 74 Noryangjin Ro
City
Dongjak
Postcode
06927
Country
Korea, Republic of

Scientific contact point

Organisation
Yuhan Corp.
Contact name
Clinical Operation Team

Public contact point

Organisation
Yuhan Corp.
Contact name
Clinical Operation Team

Third parties 2

OrganisationCity, countryDuties
Parexel International (IRL) Limited
ORG-100022780
 Dublin 2, Ireland On site monitoring, Code 10, Code 12, Code 13, Code 14, Code 5, Code 8, Code 9
Excelya Greece CRO Single Member S.A.
ORG-100009224
 Nea Filadelfia, Greece On site monitoring, Code 12

Locations

2 EU/EEA countries · 4 investigational sites

By country

CountryMS statusPlanned subjectsSites
Greece Ended 2 2
Hungary Ended 3 2
Rest of world
Russian Federation, Ukraine, Thailand, Philippines, Australia, Malaysia, Turkey, Singapore, Serbia, Korea, Republic of
 — 66 —

Investigational sites

Greece

2 sites · Ended
Theageneio Cancer Hospital
30007: Pulmonary-Oncology Clinic, Simeonidi Alex 2, 546 39, Thessaloniki
University General Hospital Attikon
30003: 2nd Propaedeutic Internal Medicine Clinic-Oncology Unit, Rimini Street 1, 124 62, Athens

Hungary

2 sites · Ended
Reformatus Pulmonologiai Centrum
36001: Onkológiai Osztály, Munkacsy Mihaly Utca 70, 2045, Torokbalint
University Of Debrecen
36004, Nagyerdei Korut 98, 4032, Debrecen

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Greece 2020-12-15 2026-04-01 2021-02-12 2021-08-13
Hungary 2020-12-16 2026-04-21 2021-02-09 2021-08-13

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 30 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_GRC Protocol Main Greek YH25448-301 Public 3.2
Protocol (for publication) D1_Protocol Main English YH25448-301 Public 3.2
Recruitment arrangements (for publication) K1_HUN Recruitment Procedure Description English YH25448-301 Public 1.0
Recruitment arrangements (for publication) K1_Recruitment arrangements Transition Filenote YH25448-301 NA
Subject information and informed consent form (for publication) L1_GRC Country ICF Addendum English YH25448-301 Public 3.0
Subject information and informed consent form (for publication) L1_GRC Country ICF Addendum Greek YH25448-301 Public 3.0
Subject information and informed consent form (for publication) L1_GRC Country ICF Future Biomedical Research English YH25448-301 Public 1.0
Subject information and informed consent form (for publication) L1_GRC Country ICF Future Biomedical Research Greek YH25448-301 Public 1.0
Subject information and informed consent form (for publication) L1_GRC Country ICF Main English YH25448-301 Public 7.0
Subject information and informed consent form (for publication) L1_GRC Country ICF Main Greek YH25448-301 Public 7.0
Subject information and informed consent form (for publication) L1_GRC Country ICF Other Cross-over English YH25448-301 Public 7.0
Subject information and informed consent form (for publication) L1_GRC Country ICF Other Cross-over Greek YH25448-301 Public 7.0
Subject information and informed consent form (for publication) L1_GRC Country ICF Other Pregnant Partner English YH25448-301 Public 1.0
Subject information and informed consent form (for publication) L1_GRC Country ICF Other Pregnant Partner Greek YH25448-301 Public 1.0
Subject information and informed consent form (for publication) L1_HUN Country ICF Addendum Hungarian YH25448-301 Public 3.0
Subject information and informed consent form (for publication) L1_HUN Country ICF Extension Hungarian YH25448-301 Public 7.0
Subject information and informed consent form (for publication) L1_HUN Country ICF Extension PIS Hungarian YH25448-301 Public 7.0
Subject information and informed consent form (for publication) L1_HUN Country ICF Main Hungarian YH25448-301 Public 7.0
Subject information and informed consent form (for publication) L1_HUN Country ICF Main PIS Hungarian YH25448-301 Public 7.0
Subject information and informed consent form (for publication) L1_HUN Country ICF Pregnant Partner Concent Form Hungarian YH25448-301 Public 1.0
Subject information and informed consent form (for publication) L1_HUN Country ICF Pregnant Partner Information Sheet Hungarian YH25448-301 Public 1.0
Subject information and informed consent form (for publication) L1_HUN Country ICF Sub Study Hungarian YH25448-301 Public 1.0
Subject information and informed consent form (for publication) L1_HUN Country ICF Sub Study PIS Hungarian YH25448-301 Public 1.0
Subject information and informed consent form (for publication) L1_HUN Subject Participation Card Hungarian YH25448-301 Public 2.1
Subject information and informed consent form (for publication) L1_HUN Subject Participation Card Justification letter English YH25448-301 Public 1.0
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC Gefitinib-ratiopharm English YH25448-301 Public NA
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC Gefitinib-ratiopharm German YH25448-301 Public NA
Synopsis of the protocol (for publication) D1_GRC Lay Protocol Synopsis Main Greek YH25448-301 Public 1.1
Synopsis of the protocol (for publication) D1_HUN Lay Protocol Synopsis Main Hungarian YH25448-301 Public 1.1
Synopsis of the protocol (for publication) D1_Lay Protocol Synopsis Main English YH25448-301 Public 1.1

Application history

4 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-07-26 Hungary Acceptable
2024-08-21
 2024-08-21
2 SUBSTANTIAL MODIFICATION SM-1 2025-03-28 Hungary Acceptable
2025-05-06
 2025-05-15
3 SUBSTANTIAL MODIFICATION SM-2 2025-09-22 Hungary Acceptable
2025-11-24
 2025-11-24
4 SUBSTANTIAL MODIFICATION SM-3 2026-01-09 Hungary Acceptable
2026-02-23
 2026-02-25

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