A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Carcinoma, Non-Small-Cell Lung Clinical Trial

— MARIPOSA  

Official title:

A Phase 3, Randomized Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib Versus Lazertinib as First-Line Treatment in Patients With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04487080
• Other study ID #: CR108856
• Secondary ID: 2020-000743-3173
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 30, 2020
• Est. completion date: June 9, 2027

Study information

• Verified date: April 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy of the amivantamab and lazertinib combination, compared with osimertinib, in participants with epidermal growth factor receptor (EGFR) mutation (Exon 19 deletions [Exon 19del] or Exon 21 L858R substitution) positive, locally advanced or metastatic non-small cell lung cancer (NSCLC).

Description:

Worldwide, lung cancer is the most commonly diagnosed cancer. In NSCLC the most prevalent actionable driver mutations result in the activation of epidermal growth factor receptor (EGFR). Osimertinib and Lazertinib are EGFR tyrosine kinase inhibitors (TKIs). Amivantamab is a novel bispecific antibody that targets the extracellular domain of both EGFR and MET and can inhibit tumor growth driven by EGFR and mesenchymal-epithelial transition (MET) receptors. Lazertinib inhibits primary activating Exon 19dell and Exon 21 L858R substitution EGFR mutations, and the EGFR T790M+ resistance mutation. The hypothesis is that the amivantamab and lazertinib combination (Arm A) will demonstrate superior PFS compared with single-agent osimertinib (Arm B). The study consists of 3 phases: Screening Phase, Treatment Phase and Follow-up Phase. Participants will undergo response evaluation criteria in solid tumors (RECIST 1.1), pharmacokinetics, and safety evaluations (adverse events, laboratory tests, vital sign measurements, physical examinations).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1074
• Est. completion date: June 9, 2027
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant must have newly diagnosed histologically or cytologically confirmed, locally advanced or metastatic non-small cell lung cancer (NSCLC) that is treatment naive and not amenable to curative therapy including surgical resection or chemoradiation

• The tumor harbors exon 19 deletions (Exon 19del) or Exon 21 L858R substitution, as detected by an food and drug administration (FDA)-approved or other validated test in a clinical laboratory improvement amendments (CLIA) certified laboratory (sites in the United states [US]) or an accredited local laboratory (sites outside of the US) in accordance with site standard of care

• Mandatory submission of unstained tissue from tumor (in a quantity sufficient to allow for central analysis of EGFR mutation status and blood (for circulating tumor deoxyribonucleic acid [ctDNA], digital droplet polymerase chain reaction [ddPCR], and pharmacogenomic analysis)

• Any toxicities from prior anticancer therapy must have resolved to common terminology criteria for adverse events (CTCAE) Grade 1 or baseline level

• Participant must have at least 1 measurable lesion, according to response evaluation criteria in solid tumors (RECIST) v1.1 that has not been previously irradiated. Measurable lesions should not have been biopsied during screening, but if only 1 non-irradiated measurable lesion exists, it may undergo a diagnostic biopsy and be acceptable as a target lesion, provided the baseline tumor assessment scans are performed at least 14 days after the biopsy

Exclusion Criteria:

• Participant has received any prior systemic treatment at any time for locally advanced Stage III or metastatic Stage IV disease (adjuvant or neoadjuvant therapy for Stage I or II disease is allowed, if administered more than 12 months prior to the development of locally advanced or metastatic disease)

• Participant has an active or past medical history of leptomeningeal disease

• Participant with untreated spinal cord compression. A participant that has been definitively treated with surgery or radiation and has a stable neurological status for at least 2 weeks prior to randomization is eligible provided they are off corticosteroid treatment or receiving low-dose corticosteroid treatment less than or equal to (<=) 10 milligrams per day (mg/day) prednisone or equivalent

• Participant has an active or past medical history of interstitial lung disease (ILD)/pneumonitis, including drug-induced or radiation ILD/pneumonitis

• Participant has known allergy, hypersensitivity, or intolerance to the excipients used in formulation of amivantamab, lazertinib, or osimertinib, or any contraindication to the use of osimertinib

• Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Amivantamab
Participants will receive amivantamab intravenously.
• Osimertinib
Participants will receive osimertinib capsules orally.
• Lazertinib
Participants will receive lazertinib tablets orally.
• Placebo
Participants will receive matching placebo orally.

Locations

Country	Name	City	State
Argentina	Centro Oncológico Korben	Buenos Aires
Argentina	Instituto Alexander Fleming	Buenos Aires
Argentina	Hospital Privado Centro Medico de Cordoba	Cordoba
Argentina	Centro Oncologico Riojano Integral (Cori)	La Rioja
Argentina	Clínica Viedma	Viedma
Australia	Flinders Medical Centre	Bedford Park
Australia	Austin Hospital	Heidelberg
Australia	Cabrini Medical Centre	Malvern
Australia	St John of God Hospital Murdoch	Murdoch
Australia	Sir Charles Gairdner Hospital	Nedlands
Australia	Westmead Hospital	Westmead
Australia	Southern Medical Day Care Centre	Wollongong
Australia	Princess Alexandra Hospital	Woolloongabba
Belgium	Cliniques Universitaires Saint Luc	Bruxelles
Belgium	Grand Hopital de Charleroi, site Notre Dame	Charleroi
Belgium	UZ Leuven	Leuven
Belgium	Clinique Saint Pierre	Ottignies
Belgium	Algemeen Ziekenhuis Delta	Roeselare
Brazil	Fundacao Pio XII	Barretos
Brazil	Cetus Oncologia	Belo Horizonte
Brazil	Ynova Pesquisa Clinica	Florianopolis
Brazil	Oncosite - Centro de Pesquisa Clínica em Oncologia Ltda	Ijui
Brazil	Liga Norte Riograndense Contra O Cancer	Natal
Brazil	UPCO Unidade de Pesquisa Clinica em Oncologia	Pelotas
Brazil	Irmandade Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Brazil	Uniao Brasileira de Educaçao e Assistencia-Hospital Sao Lucas da PUCRS	Porto Alegre
Brazil	Instituto D Or de Pesquisa e Ensino (IDOR)	Rio de Janeiro
Brazil	Ministerio da Saude - Instituto Nacional do Cancer	Rio De Janeiro
Brazil	Oncoclinicas Rio de Janeiro S A	Rio de Janeiro
Brazil	Fundacao Antonio Prudente A C Camargo Cancer Center	Sao Paulo
Brazil	Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo	Sao Paulo
Brazil	Núcleo de Pesquisa São Camilo	Sao Paulo
Brazil	IOS - Instituto de Oncologia de Sorocaba Dr. Gilson Delgado	Sorocaba
Brazil	Hospital Evangélico de Cachoeiro de Itapemirim	Vitoria
Canada	William Osler Health System	Brampton	Ontario
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	McGill University Health Centre	Montreal	Quebec
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
China	Beijing Cancer Hospital	Beijing
China	Beijing Chest hospital, Capital medical university	Beijing
China	Beijing Friendship Hospital Capital Medical University	Beijing
China	Chinese PLA General Hospital	Beijing
China	Jilin cancer hospital	Changchun
China	Hunan Cancer hospital	Changsha
China	The First People's Hospital Of Changzhou	Changzhou
China	Sichuan Cancer Hospital	Chengdu
China	West China Hospital Sichuan University	Chengdu
China	Southwest Hospital	ChongQing
China	The First Affiliated Hospital, Sun Yat-sen University	Guang Zhou
China	Sun Yat-Sen Memorial Hospital Sun Yat-sen University	Guangzhou
China	Zhejiang Cancer Hospital	Hang Zhou
China	Second Affiliated Hospital, School of Medicine, Zhejiang University	Hangzhou
China	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou
China	The Second Affiliated Hospital of Zhejiang University College of Medicine	Hangzhou
China	Harbin medical university cancer hospital	Harbin
China	Huizhou Municipal Central Hospital	Huizhou
China	Taizhou Hospital of Zhejiang Province	Linhai
China	Nantong Tumor Hospital	Nantong
China	Fudan University Shanghai Cancer Center	Shanghai
China	Ruijin Hospital, Shanghai Jiao Tong University	Shanghai
China	Shanghai Chest Hospital	Shanghai
China	Shanghai East Hospital	Shanghai
China	Shengjing Hospital of China Medical University	Shenyang
China	Tianjin Medical University General Hospital	Tianjin
China	Cancer Hospital of Xinjiang Medical University	Urumchi
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou
China	TongJi Hospital of TongJi Medical College of Huazhong University of Science & Technology	Wuhan
China	The First Affiliated Hospital of Xian Jiaotong University	XI An
China	Yantai Yuhuangding Hospital	Yantai
China	Henan Cancer Hospital	Zhengzhou
France	Institut Bergonié	Bordeaux
France	Hospices Civils de Lyon HCL	Bron
France	CHU de Grenoble Hopital Albert Michallon	La Tronche
France	Institute Coeur Poumon	Lille
France	CHU de Limoges	Limoges
France	Hopital Nord	Marseille Cedex 20
France	Hopital Tenon	Paris
France	Institut Curie	Paris
France	CHU Bordeaux	Pessac
France	CHU Nantes	Sain-Herblain
France	HIA Begin	Saint Mande
France	CHU Bretonneau	Tours
France	Institut Gustave Roussy	Villejuif Cedex
Germany	Zentralklinik Bad Berka GmbH	Bad Berka
Germany	Helios Klinikum Emil von Behring GmbH	Berlin
Germany	Universitaetsklinikum Essen	Essen
Germany	Asklepios Klinik Gauting GmbH - Asklepios Fachkliniken Munchen-Gauting	Gauting
Germany	Städtisches Krankenhaus Martha-Maria Halle-Dölau gGmbH	Halle (Saale)
Germany	Thoraxklinik am Universitatsklinikum Heidelberg	Heidelberg
Germany	Onkologische Schwerpunktpraxis	Heilbronn
Germany	Kliniken der Stadt Koeln gGmbH	Koeln
Germany	POIS Leipzig GbR	Leipzig
Germany	Pius-Hospital Oldenburg	Oldenburg
Germany	Robert-Bosch-Krankenhaus - Klinik Schillerhoehe	Stuttgart
Hungary	Orszagos Koranyi Tbc es Pulmonologiai Intezet	Budapest
Hungary	Veszprém Megyei Tudogyógyintézet	Farkasgyepü
Hungary	Mátrai Gyógyintézet-Bronchológia	Gyöngyös
Hungary	Fejer Varmegyei Szent Gyorgy Egyetemi Oktatokorhaz	Szekesfehervar
Hungary	Markusovszky Egyetemi Oktatokorhaz	Szombathely
Hungary	Tudogyogyintezet Torokbalint	Torokbalint
India	Basavatarakam Indo-American Hospital	Hyderabad
India	Tata Medical Center	Kolkata
India	Tata Memorial Hospital	Mumbai
India	HCG Manavta Cancer Centre	Nasik
India	Noble Hospital Pvt Ltd	Pune
Israel	Rambam Health Corporation	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Meir Medical Center	Kfar Saba
Israel	Rabin Medical Center	Petah Tikva
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	Tel-Aviv Sourasky Medical Center	Tel-Aviv
Italy	Ospedale San Giuseppe Moscati di Avellino	Avellino
Italy	Azienda Ospedaliero Univ. Policlinico Gaspare Rodolico	Catania
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola
Italy	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	Milano
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	Istituto Europeo di Oncologia	Milano
Italy	San Gerardo Hospital	Monza
Italy	Ospedale Monaldi	Napoli
Italy	Aou San Luigi Gonzaga	Orbassano
Italy	Ospedale S. Maria Delle Croci	Ravenna
Italy	Irccs Gemelli	Roma
Italy	Istituto Clinico Humanitas	Rozzano
Japan	Juntendo University Hospital	Bunkyo Ku
Japan	National Cancer Center Hospital	Chuo Ku
Japan	National Hospital Organization Kyushu Medical Center	Fukuoka
Japan	National Hospital Organization Himeji Medical Center	Himeji
Japan	Kansai Medical University Hospital	Hirakata
Japan	Kanazawa University Hospital	Kanazawa
Japan	National Cancer Center Hospital East	Kashiwa
Japan	Kurume University Hospital	Kurume
Japan	Matsusaka Municipal Hospital	Matsusaka
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Okayama University Hospital	Okayama
Japan	Kindai University Hospital	Osaka Sayama shi
Japan	National Hospital Organization Shibukawa Medical Center	Shibukawa
Japan	National Hospital Organization Tokyo Medical Center	Tokyo
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	Ehime University Hospital	Toon-shi
Japan	National Hospital Organization Osaka Toneyama Medical Center	Toyonaka-shi
Japan	Wakayama Medical University Hospital	Wakayama
Japan	National Hospital Organization Iwakuni Clinical Center	Yamaguchi
Japan	National Hospital Organization Yamaguchi Ube Medical Center	Yamaguchi
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea Seoul St. Mary's Hospital	Seoul
Malaysia	Hospital Pulau Pinang	George Town
Malaysia	Hospital Sultan Ismail	Johor Bahru
Malaysia	Hospital Kuala Lumpur	Kuala Lumpur
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Hospital Tengku Ampuan Afzan	Kuantan
Malaysia	Beacon Hospital Sdn Bhd	Petaling Jaya
Mexico	Médica Sur	Ciudad de Mexico
Mexico	Mexico Centre for Clinical Research, S.A. de C.V.	Ciudad de Mexico
Mexico	Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara
Mexico	CIMOVA, Morals Vargas Centro de Investigación SC	Leon
Mexico	Health Pharma Professional Research	Mexico
Mexico	Instituto Nacional de Cancerologia	Mexico
Mexico	i Can Oncology Center	Monterrey
Mexico	Oncologia Integral Satelite	Naucalpan
Netherlands	Rijnstate Ziekenhuis	Arnhem
Netherlands	Ziekenhuis St Jansdal	Harderwijk
Netherlands	UMC Radboud	Nijmegen
Netherlands	Jeroen Bosch Ziekenhuis	s-Hertogenbosch
Poland	Centrum Onkologii im. Prof. F. Lukaszczyka	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Szpitale Pomorskie Sp z o o	Gdynia
Poland	Warminsko-Mazurskie Centrum Chorob Pluc w Olsztynie	Olsztyn
Poland	Private Specialist Hospitals - MedPolonia	Poznan
Poland	Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy	Warszawa
Portugal	Centro Hospitalar Lisboa Norte EPE - Hospital Pulido Valente	Lisboa
Portugal	Centro Hospitalar Universitario do Porto, EPE	Porto
Portugal	Hospital CUF Porto	Porto
Portugal	Instituto Portugues de Oncologia	Porto
Puerto Rico	Pan American Center for Oncology Trials LLC	Rio Piedras
Russian Federation	Irkutsk Regional Oncology Dispensary	Irkutsk
Russian Federation	Moscow City Oncology Hospital ? 62	Krasnogorsk
Russian Federation	Krasnoyarsk Regional Oncology Dispensary	Krasnoyarsk
Russian Federation	Leningrad Regional Oncology Dispensary	Kuzmolovsky
Russian Federation	MCK	Moscow
Russian Federation	City Clinical Hospital #1	Nalchik
Russian Federation	Nizhny Novgorod Regional Oncological Dispensary	Nizhniy Novgorod
Russian Federation	Omsk Clinical Oncology Dispensary	Omsk
Russian Federation	Current medical technologies	Saint Petersburg
Russian Federation	N.N. Petrov Research Institute Of Oncology	Saint Petersburg
Russian Federation	Oncology Medical Clinics AV Medical group	St-Petersburg
Russian Federation	Tambov Regional Oncology Clinical Dispansary	Tambov
Russian Federation	Tomsk Cancer Research Institute	Tomsk
Russian Federation	Bashkir State Medical University	Ufa
Russian Federation	Yaroslavl Regional Clinical Oncology Hospital	Yaroslavl
Spain	Hosp. Univ. A Coruna	A Coruna
Spain	Inst. Cat. D'Oncologia-Badalona	Badalona
Spain	Hosp. de La Santa Creu I Sant Pau	Barcelona
Spain	Hosp. Univ. Quiron Dexeus	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Univ. de Burgos	Burgos
Spain	Institut Català D'Oncologia Girona	Girona
Spain	Hosp. Gral. Univ. Gregorio Maranon	Madrid
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Univ. La Paz	Madrid
Spain	Hosp. Univ. Pta. de Hierro Majadahonda	Majadahonda
Spain	Hosp. Regional Univ. de Malaga	Malaga
Spain	Clinica Univ. de Navarra	Pamplona
Spain	Hosp. Virgen Del Rocio	Seville
Spain	Hosp. Gral. Univ. Valencia	Valencia
Spain	Hosp. Clinico Univ. Lozano Blesa	Zaragoza
Taiwan	Chang Gung Medical Foundation	Kaohsiung
Taiwan	E-DA Hospital	Kaohsiung
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Taipei Medical University Shuang Ho Hospital	New Taipei
Taiwan	China Medical University Hospital	Taichung
Taiwan	Chung Shan Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei City
Thailand	Phramongkutklao Hospital and Medical College	Bangkok
Thailand	Siriraj Hospital	Bangkok
Thailand	Chiang Mai University	Chiangmai
Thailand	Songklanagarind Hospital, Prince of Songkla University	Songkla
Turkey	Adana City Hospital	Adana
Turkey	Baskent University Medical Faculty Adana Application and Research Center	Adana
Turkey	Ankara Bilkent City Hospital	Ankara
Turkey	Gazi University Hospital	Ankara
Turkey	Trakya University Medical Faculty	Edirne
Turkey	Istanbul Universitesi Cerrahpasa Tip Fakultesi Ic Hastaliklari Anabilim Dali Medikal Onkoloji Bd	Istanbul
Turkey	Medipol Mega University Hospital	Istanbul
Turkey	T.C. Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi	Istanbul
Turkey	Medical Point	Izmir
Turkey	Necmettin Erbakan University Meram Medical Faculty	Konya
Ukraine	Dnipropetrovsk State Medical Academy, Dnipropetrovsk City Multifield Clinical Hospital # 4	Dnipro
Ukraine	Municipal non-profit enterprise 'Regional Center of Oncology'	Kharkiv
Ukraine	Medical Center 'Ok Clinic' of LLC 'International Institute of Clinical Studies'	Kyiv
Ukraine	National Cancer Institute	Kyiv
Ukraine	Municipal Oncology Centre of Uzhgorod Central Municipal Clinical Hospitlal	Uzhgorod
United Kingdom	Edinburgh Cancer Centre Western General	Edinburgh
United Kingdom	Chelsea And Westminster Hospital	London
United Kingdom	The Royal Marsden NHS Trust	London
United Kingdom	UCL Cancer Institute	London
United Kingdom	Christie NHS Foundation Trust	Manchester
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	The Royal Marsden NHS Trust	Sutton
United States	University Cancer & Blood Center, LLC	Athens	Georgia
United States	Texas Oncology P.A.	Austin	Texas
United States	Maryland Oncology Hematology, PA	Columbia	Maryland
United States	Henry Ford Hospital	Detroit	Michigan
United States	Astera Cancer Care	East Brunswick	New Jersey
United States	Minnesota Oncology Hematology, P.A.	Edina	Minnesota
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Arizona Oncology Associates, PC - HAL	Goodyear	Arizona
United States	Oncology Consultants - Texas	Houston	Texas
United States	Cancer Specialists of North Florida	Jacksonville	Florida
United States	Rocky Mountain Cancer Centers	Lone Tree	Colorado
United States	City of Hope Long Beach Elm	Long Beach	California
United States	East Jefferson General Hospital	Metairie	Louisiana
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	University of California Irvine	Orange	California
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Yuma Regional Medical Center	Yuma	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  France,  Germany,  Hungary,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  Poland,  Portugal,  Puerto Rico,  Russian Federation,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) According to RECIST v1.1 by Blinded Independent Central Review (BICR)	PFS is defined as the time from randomization until the date of objective disease progression or death, whichever occurred first, based on BICR using response evaluation criteria in solid tumors (RECIST) v1.1.	Up to approximately 42 months
Secondary	Overall Survival (OS)	Overall Survival is defined as the time from the date of randomization to the date of participant's death due to any cause.	Up to approximately 60 months (time from the date of randomization until the date of death due to any cause)
Secondary	Objective Response Rate (ORR)	ORR is defined as the percentage of participants who achieve either a complete response (CR) or partial response (PR) as defined by BICR using RECIST v1.1 criteria.	Up to approximately 42 months
Secondary	Duration of Response (DOR)	DOR is 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, only for participants who achieve CR or PR as determined by the investigator using RECIST v1.1 criteria.	Up to approximately 42 months
Secondary	Progression-Free Survival After First Subsequent Therapy (PFS2)	The PFS2 is defined as the time from randomization until the date of second objective disease progression, after initiation of subsequent anticancer therapy, based on investigator assessment (after that used for PFS) or death, whichever comes first.	Up to approximately 42 months
Secondary	Time to Symptomatic Progression (TTSP)	TTSP is defined as the time from randomization to documentation in the electronic case report form (eCRF) of any of the following (whichever occurs earlier): onset of new symptoms or symptom worsening that is considered by the investigator to be related to lung cancer and requires either a change in anticancer treatment and/or clinical intervention to manage symptoms.	Up to approximately 42 months
Secondary	Intracranial PFS	Intracranial PFS is defined as the time from randomization until the date of objective intracranial disease progression or death, whichever comes first, based on BICR using RECIST v1.1.	Up to approximately 42 months
Secondary	Incidence and Severity of Adverse Events (AEs)	Incidence and severity of treatment emergent adverse events (TEAEs) will be reported. Any adverse event occurring at or after the initial administration of study treatment through the day of last dose plus 30 days, or until the start of subsequent anticancer therapy (if earlier), is considered to be treatment emergent.	Up to approximately 60 months
Secondary	Number of Participants with Clinical Laboratory Abnormalities	Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, blood coagulation, and urine samples) will be reported.	Up to approximately 60 months
Secondary	Number of Participants with Vital Signs Abnormalities	Number of participants with vital signs abnormalities (temperature, heart rate, respiratory rate, oxygen saturation, blood pressure) will be reported.	Up to approximately 60 months
Secondary	Number of Participants with Physical Examination Abnormalities	Number of participants with physical examination abnormalities will be reported.	Up to approximately 60 months
Secondary	Serum Concentration of Amivantamab	Serum samples will be analyzed to determine concentrations of amivantamab.	Up to approximately 42 months
Secondary	Plasma Concentration of Lazertinib	Plasma samples will be analyzed to determine concentrations of lazertinib.	Up to approximately 42 months
Secondary	Number of Participants with Anti-Amivantamab Antibodies	Number of participants with antibodies to amivantamab will be reported.	Up to approximately 42 months
Secondary	Change from Baseline in Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NCSLC-SAQ)	The NSCLC-SAQ contains 7 items that assess cough, pain, dyspnea, fatigue, and poor appetite over a 7-day recall period. Each multi-item scale and individual item will be summarized using count and percent by visit.	Baseline Up to approximately 42 months
Secondary	Change from Baseline in European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)	EORTC-QLQ-C30 is a core 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies.	Baseline Up to approximately 42 months