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

• Sponsor: Yuhan Corporation (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04248829
• Collaborator: (none)
• Enrollment: 393
• Locations: 80
• Arms: 2
• Anticipated Duration (Months): 51.6
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: Lazertinib 240 mg/160 mg; Drug: Gefitinib 250 mg; Drug: Lazertinib-matching placebo 240 mg/160 mg; Drug: Gefitinib-matching placebo 250 mg	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 393 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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 lazertinibApproximately 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
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Feb 13, 2020
• Anticipated Primary Completion Date: Dec 1, 2022
• Anticipated Study Completion Date: Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lazertinib + Gefitinib-matching placebo 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; 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; Other Names: YH25448 240 mg/160 mg ; Drug: Gefitinib-matching placebo 250 mg; The initial dose for Gefitinib-matching placebo (250 mg once daily) cannot be reduced to a lower dose; Other Names: Iressa-matching placebo 250 mg
Active Comparator: Gefitinib + Lazertinib-matching placebo 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; The initial dose for Gefitinib (250 mg once daily) cannot be reduced to a lower dose; Other Names: Iressa 250 mg ; Drug: 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; Other Names: YH25448-matching placebo 240 mg/160 mg

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) according to RECIST v1.1 by Investigator assessment [The primary analysis of PFS based on investigator assessment will occur when PFS maturity is observed at approximately 27 months after the first patient is randomized]

   To assess the efficacy of lazertinib compared with gefitinib as measured by PFS

Secondary Outcome Measures

1. Objective Response Rate (ORR) according to RECIST v1.1 by Investigator assessments [ORR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized]

   To further assess the efficacy of lazertinib compared with gefitinib

2. Duration of Response (DoR) according to RECIST v1.1 by Investigator assessments [DoR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized]

   To further assess the efficacy of lazertinib compared with gefitinib

3. Disease Control Rate (DCR) according to RECIST v1.1 by Investigator assessments [DCR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized]

   To further assess the efficacy of lazertinib compared with gefitinib

4. Depth of Response according to RECIST v1.1 by Investigator assessments [Depth of Response analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized]

   To further assess the efficacy of lazertinib compared with gefitinib

5. Time to Response according to RECIST v1.1 by Investigator assessments [Time to Response analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized]

   To further assess the efficacy of lazertinib compared with gefitinib

6. Overall survival (OS) [OS will be analyzed at 2 time points: when PFS maturity is observed at approximately 27 months after the first patient is randomized, and when OS maturity is observed at approximately 45 months after the first patient is randomized]

   To assess OS of lazertinib compared with gefitinib

7. Plasma concentrations of lazertinib [Plasma concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized]

   To characterize the pharmacokinetics (PK) of lazertinib

8. Cerebrospinal fluid (CSF) concentrations of lazertinib [CSF concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized]

   To characterize the PK of lazertinib

9. Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 items (QLQ-C30) [EORTC-QLQ-C30 analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized]

   The EORTC QLQ-C30 consists of 30 items and measures cancer patients' 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 patients (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

10. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Lung Cancer 13 items (EORTC QLQ-LC13) [EORTC QLQ-LC13 analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized]

    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.

11. Change From Baseline in Euro-Quality of Life-5 Dimension-5 level (EQ-5D-5L) [EQ-5D-5L analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized]

    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 patients 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.

Other Outcome Measures

1. Intracranial PFS according to RECIST v1.1 by Investigator assessment and blinded independent central review (BICR) [Intracranial PFS based on Investigator assessment and BICR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized]

   To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with brain metastases (BM) at baseline

2. Intracranial ORR according to RECIST v1.1 by Investigator assessments and BICR [Intracranial ORR based on Investigator assessment and BICR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized]

   To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with BM at baseline

3. Intracranial DoR according to RECIST v1.1 by Investigator assessment and BICR [Intracranial DoR based on Investigator assessment and BICR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized]

   To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with BM at baseline

4. Intracranial DCR according to RECIST v1.1 by Investigator assessment and BICR [Intracranial DCR based on Investigator assessment and BICR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized]

   To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with BM at baseline

5. Depth of intracranial response according to RECIST v1.1 by Investigator assessment and BICR [Depth of intracranial response based on Investigator assessment and BICR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized]

   To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with BM at baseline

6. Time to intracranial response according to RECIST v1.1 by Investigator assessment and BICR [Time to intracranial response analysis based on Investigator assessment and BICR will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized]

   To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with BM at baseline

7. PFS according to RECIST v1.1 by Investigator assessment [PFS analysis will occur when OS maturity is observed at approximately 45 months from the first dosing date of lazertinib]

   To assess the efficacy of lazertinib in the cross-over arm

8. ORR according to RECIST v1.1 by Investigator assessments [ORR analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized]

   To assess the efficacy of lazertinib in the cross-over arm

9. DoR according to RECIST v1.1 by Investigator assessments [DoR analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized]

   To assess the efficacy of lazertinib in the cross-over arm

10. DCR according to RECIST v1.1 by Investigator assessments [DCR analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized]

    To assess the efficacy of lazertinib in the cross-over arm

11. Depth of Response according to RECIST v1.1 by Investigator assessments [Depth of Response analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized]

    To assess the efficacy of lazertinib in the cross-over arm

12. Time to Response according to RECIST v1.1 by Investigator assessments [Time to Response analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized]

    To assess the efficacy of lazertinib in the cross-over arm

13. Change from baseline for EGFR mutation status in plasma samples [EGFR mutation status in plasma samples analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized]

    To compare plasma-derived cfDNA EGFR mutation status at baseline and at progression

14. Change from baseline for EGFR mutation status in tumor samples [EGFR mutation status in tumor samples analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized]

    To compare the tumor sample EGFR mutation status at baseline and from an optional tumor sample taken at progression

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
2	Eugenideio Therapeutirio - Ongcology Department	Athens		Greece	11528
3	Attikon Hospital	Athens		Greece	12462
4	Theageneio Anticancer Hospital of Thessaloniki	Thessaloníki		Greece	54007
5	Debreceni Egyetem	Debrecen		Hungary	H-4012
6	Törökbálinti Tüdőgyógyintézet	Törökbálint		Hungary	2045
7	Chungbuk National University Hospital	Cheongju-si	Chungcheongbuk-do	Korea, Republic of	28644
8	The Catholic University of Korea, Bucheon St. Mary's Hospital	Bucheon-si	Gyeonggi-do	Korea, Republic of	14647
9	National Cancer Center	Goyang-si	Gyeonggi-do	Korea, Republic of	10408
10	CHA Bundang Medical Center, CHA University	Seongnam-si	Gyeonggi-do	Korea, Republic of	13496
11	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
12	The Catholic University of Korea, St. Vincent's Hospital	Suwon-si	Gyeonggi-do	Korea, Republic of	16247
13	Ajou University Hospital	Suwon-si	Gyeonggi-do	Korea, Republic of	16499
14	Gyeongsang National University Hospital	Jinju-si	Gyeongsangnam-do	Korea, Republic of	52727
15	Inje University Haeundae Paik Hospital	Busan		Korea, Republic of	48108
16	Yeungnam University Medical Center	Daegu		Korea, Republic of	42415
17	Keimyung University Dongsan Medical Center	Daegu		Korea, Republic of	42601
18	Gachon University Gil Medical Center	Incheon		Korea, Republic of	21565
19	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
20	Seoul National University Hospital	Seoul		Korea, Republic of	03080
21	Kangbuk Samsung Hospital	Seoul		Korea, Republic of	03181
22	The Catholic University of Korea, Eunpyeong St.Mary's Hospital	Seoul		Korea, Republic of	03312
23	Severance Hospital	Seoul		Korea, Republic of	03722
24	Asan Medical Center	Seoul		Korea, Republic of	05505
25	Samsung Medical Center	Seoul		Korea, Republic of	06351
26	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06591
27	SMG-SNU Boramae Medical Center	Seoul		Korea, Republic of	07061
28	Ulsan University Hospital	Ulsan		Korea, Republic of	44033
29	Hospital Sultan Ismail	Johor Bahru	Johor	Malaysia	81100
30	Hospital Raja Perempuan Zainab Ii	Kota Bahru	Kelantan	Malaysia	15586
31	Hospital Tengku Ampuan Afzan	Kuantan	Pahang	Malaysia	25100
32	Hospital Pulau Pinang	George Town	Pulau Pinang	Malaysia	10400
33	Hospital Umum Sarawak	Kuching	Sarawak	Malaysia	10450
34	University Malaya Medical Centre	Kuala Lumpur	Selangor	Malaysia	59100
35	Manila Doctors Hospital - Clinical Trial Office	Manila	Quezon	Philippines	1000
36	Perpetual Succour Hospital	Cebu		Philippines	6000
37	Philippine General Hospital	Manila		Philippines	1000
38	Arkhangelsk Regional Clinical Oncological Dispensary	Arkhangel'sk	Arkhangel'skaya Oblast'	Russian Federation	163045
39	GBUZ of Nizhny Novgorod region Clinical diagnostic center	Nizhny Novgorod	Nizhegorodskaya Oblast'	Russian Federation	603006
40	GAUZ Republican clinical oncology dispensary of the Ministry	Kazan		Russian Federation	420029
41	Republic Clinical Oncology Despensary	Kazan		Russian Federation	420029
42	Medincentre (GLAVUPDK)	Moscow		Russian Federation	119034
43	VitaMed LLC	Moscow		Russian Federation	121309
44	MBUZ City Clinical Hospital #1	Novosibirsk		Russian Federation
45	Budgetary Healthcare Institution of Omsk Region "Clinical Oncology Dispensary"	Omsk		Russian Federation	644013
46	Private medical institution "Euromedservice"	Pushkin		Russian Federation	196603
47	First St. Petersburg State Medical University n. a. Pavlov	Saint Petersburg		Russian Federation	197022
48	LLC "Eurocityclinic"	Saint Petersburg		Russian Federation	197022
49	Limited Liability Company "AV Medical Group" - Oncology	Saint Petersburg		Russian Federation	197082
50	Saint-Petersburg City Clinical Oncology Dispensary	Saint Petersburg		Russian Federation	198255
51	GBUZ "Regional clinical oncologic dispensary of Volgograd"	Volgograd		Russian Federation	400138
52	Yaroslavl regional oncology hospital	Yaroslavl		Russian Federation	150054
53	Institute for Pulmonary Diseases of Vojvodina	Sremska Kamenica	Vojvodina	Serbia	21204
54	Institute for Oncology and Radiology of Serbia	Belgrade		Serbia	11000
55	Clinical Hospital Center "Bezanijska Kosa"	Belgrade		Serbia	11080
56	National University Hospital	Singapore		Singapore	119074
57	National Taiwan University Hospital	Taipei		Taiwan	10002
58	Taipei Veterans General Hospital	Taipei		Taiwan	11217
59	Ramathibodi Hospital, Mahidol University	Bangkok		Thailand	10400
60	Siriraj Hospital	Bangkok		Thailand	10700
61	Chiang Mai University - Faculty of Medicine	Chiang Mai		Thailand	50200
62	Prince of Songkla University	Hat Yai		Thailand	90110
63	Srinagarind Hospital, Khon Kaen University	Khon Kaen		Thailand	40002
64	Adana Baskent Practice and Research Hospital	Adana		Turkey	1120
65	Cukurova University Medical Faculty	Adana		Turkey	1330
66	Ankara Liv Hospital	Ankara		Turkey	06680
67	Hacettepe University Medical Faculty - Medical Oncology	Ankara		Turkey	6230
68	Trakya University Medical Faculty	Edirne		Turkey	22030
69	Istanbul Medeniyet University Goztepe Training and Research Hospital - Medical Oncology	Istanbul		Turkey	34722
70	Izmir Medical Park Hospital - Medical Oncology	İzmir		Turkey	35575
71	Kocaeli University Medical Faculty	Kocaeli		Turkey	41380
72	Inonu University Turgut Ozal Medical Center	Malatya		Turkey	44280
73	Komunalne nekomertsiine pidpryiemstvo Kharkivskoi oblasnoi rady "Oblasnyi klinichnyi spetsializovanyi dyspanser radiatsiinoho zakhystu naselennia" - khirurhichne viddilennia	Kharkiv	Kharkivs'ka Oblast'	Ukraine	61166
74	Tsentralna miska klinichna likarnia	Úzhgorod	Zakarpats'ka Oblast'	Ukraine	88000
75	Oblasne komunalne nekomertsiine pidpryiemstvo "Bukovynskyi klinichnyi onkolohichnyi tsentr"	Chernivtsi		Ukraine	58013
76	Komunalne nekomertsiine pidpryiemstvo "Miska klinichna likarnia №4" Dniprovskoi miskoi rady"	Dnipro		Ukraine	49102
77	Kyiv City Clinical Oncology Center - Department of Chemotherapy	Kyiv		Ukraine	3115
78	Sumskyi oblasnyi klinichnyi onkolohichnyi dyspanser	Sumy		Ukraine	40022
79	Podilskyi rehionalnyi tsentr onkolohii, viddilennia khimioterapii	Vinnytsia		Ukraine	21029
80	Medychnyi tsentr Tovarystva z obmezhenoiu vidpovidalnistiu "Onkolaif"	Zaporizhzhia		Ukraine	69059

Sponsors and Collaborators

• Yuhan Corporation

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yuhan Corporation
• ClinicalTrials.gov Identifier: NCT04248829
• Other Study ID Numbers: YH25448-301
• First Posted: Jan 30, 2020
• Last Update Posted: Jun 30, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Yuhan Corporation: 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
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Gefitinib; Lazertinib

Study Results

No Results Posted as of Jun 30, 2022