A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure

Carcinoma, Non-Small-Cell Lung Clinical Trial

— MARIPOSA-2  

Official title:

A Phase 3, Open-Label, Randomized Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04988295
• Other study ID #: CR109061
• Secondary ID: 2021-001825-3361
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 17, 2021
• Est. completion date: December 8, 2025

Study information

• Verified date: June 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 adding lazertinib to amivantamab, carboplatin, and pemetrexed (LACP/ACP-L dosing strategies) and amivantamab, carboplatin and pemetrexed (ACP) compared with carboplatin and pemetrexed (CP) in participants with locally advanced or metastatic epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R substitution non-small cell lung cancer (NSCLC) after osimertinib failure. The purpose of the extension cohort is to further describe the safety and efficacy for the ACP-L dosing schedule versus ACP with additional data. After completion of the primary analysis, the study may eventually transition to an open-label extension (OLE) or long-term extension (LTE) phase during which participants will have the option to continue their assigned treatment.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 776
• Est. completion date: December 8, 2025
• Est. primary completion date: July 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant must have at least 1 measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, that has not been previously irradiated

• Participant must have histologically or cytologically confirmed, locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC), characterized at or after the time of locally advanced or metastatic disease diagnosis by either epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R mutation

• A participant with a history of brain metastases must have had all lesions treated as clinically indicated (that is, no current indication for further definitive local therapy). Any definitive local therapy to brain metastases must have been completed at least 14 days prior to randomization and the participant can be receiving no greater than10 milligrams (mg) prednisone or equivalent daily for the treatment of intracranial disease

• Participant must have Eastern Cooperative Oncology Group (ECOG) status of 0 or 1

• Any toxicities from prior systemic anticancer therapy must have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 Grade 1 or baseline level (except for alopecia [any grade], Grade <= 2 peripheral neuropathy, or Grade <= 2 hypothyroidism stable on hormone replacement)

• A participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study

• Participant must have progressed on or after osimertinib monotherapy as the most recent line of treatment. Osimertinib must have been administered as either the first-line treatment for locally advanced or metastatic disease or in the second- line setting after prior treatment with first- or second-generation EGFR tyrosine kinase inhibitor (TKI) as a monotherapy. Participants who received either neoadjuvant and/or adjuvant treatment of any type are eligible if progression to locally advanced or metastatic disease occurred at least 12 months after the last dose of such therapy and then the participant progressed on or after osimertinib in the locally advanced or metastatic setting. Treatment with osimertinib must be discontinued at least 8 days (4 half-lives) prior to randomization (that is last dose no later than Day -8)

Exclusion Criteria:

• Participant received radiotherapy for palliative treatment of NSCLC less than 14 days prior to randomization

• Participant with symptomatic or progressive brain metastases

• Participant has history of or current evidence of leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation

• Participant has known small cell transformation

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

• Participant has a history of clinically significant cardiovascular disease including, but not limited to diagnosis of deep vein thrombosis or pulmonary embolism within 4 weeks prior to randomization; myocardial infarction; unstable angina; stroke; transient ischemic attack; coronary/peripheral artery bypass graft; or acute coronary syndrome. Participant has a significant genetic predisposition to venous thromboembolic events. Participant has a prior history of venous thromboembolic events and is not on appropriate therapeutic anticoagulation as per National Comprehensive Cancer Network or local guidelines

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Lazertinib
Lazertinib will be administered orally.
• Amivantamab
Amivantamab will be administered as an IV infusion.
• Pemetrexed
Pemetrexed will be administered as an IV infusion.
• Carboplatin
Carboplatin will be administered as an IV infusion.

Locations

Country	Name	City	State
Argentina	CEMIC (Centro de Educación Médica e Investigaciones Clínicas)	Caba
Argentina	Centro Medico Fleischer	Caba
Argentina	CINME Centro de Investigaciones Metabolicas	Caba
Argentina	IADT Instituto Argentino de Diagnostico y Tratamiento	Caba
Argentina	Cemaic - Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica	Córdoba
Argentina	Hospital Privado Universitario de Córdoba	Córdoba
Argentina	Hospital Privado de la Comunidad	Mar del Plata
Argentina	Clínica Viedma	Viedma
Belgium	Grand Hopital de Charleroi, site Notre Dame	Charleroi
Belgium	UZA	Edegem
Belgium	UZ Gent	Gent
Belgium	Jessa Ziekenhuis - Campus Virga Jesse	Hasselt
Belgium	UZ Leuven	Leuven
Belgium	CHU Sart-Tilman	Liege
Belgium	Clinique Saint Pierre	Ottignies
Brazil	Cetus Oncologia	Belo Horizonte
Brazil	CIONC Centro Integrado de Oncologia de Curitiba	Curitiba
Brazil	Ynova Pesquisa Clinica	Florianopolis
Brazil	Fundação São Francisco Xavier	Ipatinga
Brazil	UPCO Unidade de Pesquisa Clinica em Oncologia	Pelotas
Brazil	Associacao Hospitalar Moinhos de Vento	Porto Alegre
Brazil	Hospital Ernesto Dornelles	Porto Alegre
Brazil	Instituto D Or de Pesquisa e Ensino (IDOR)	Rio de Janeiro
Brazil	Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)	Rio de Janeiro
Brazil	Oncoclinicas Rio de Janeiro S A	Rio de Janeiro
Brazil	Hospital Sao Rafael	Salvador
Brazil	Nucleo de Oncologia da Bahia	Salvador
Brazil	CEPHO - Centro de Estudos e Pesquisa de Hematologia e Oncologia	Santo André
Brazil	Fundacao Antonio Prudente A C Camargo Cancer Center	Sao Paulo
Brazil	Hospital Alemao Oswaldo Cruz	Sao Paulo
Brazil	Hospital Paulistano	Sao Paulo
Brazil	Real e Benemerita Associacao Portuguesa de Beneficencia	Sao Paulo
Brazil	Hospital Nove de Julho	São Paulo
Brazil	Onco Star SP Oncologia Ltda	São Paulo
Brazil	IOS - Instituto de Oncologia de Sorocaba Dr. Gilson Delgado	Sorocaba
Brazil	COT - Centro Oncologico do Triangulo S.A	Uberlandia
Bulgaria	Multifunctional Hospital for Active Treatment 'Serdika'	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment 'Tokuda Hospital Sofia'	Sofia
Bulgaria	Specialized Hospital for Active Treatment in Oncology	Sofia
Bulgaria	UMHAT Sofia Med	Sofia
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	McGill University Health Centre	Montreal	Quebec
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
China	Beijing Cancer Hospital	Beijing
China	Beijing Chest hospital, Capital medical university	Beijing
China	Cancer Hospital, Chinese Academy of Medical Sciences	Beijing
China	Chinese PLA General Hospital	Beijing
China	Peking University People s Hospital	Beijing
China	Hunan Cancer hospital	Changsha
China	Sichuan Cancer Hospital	Chengdu
China	West China Hospital Sichuan University	Chengdu
China	Chongqing University Cancer Hospital	Chongqing
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	Affiliated Hospital of North Sichuan Medical College	Nanchong
China	Fudan University Shanghai Cancer Center	Shanghai
China	Ruijin Hospital Shanghai Jiao Tong University	Shanghai
China	Shanghai East Hospital	Shanghai
China	Cancer Hospital Chinese Academy of Medical Sciences	Shenzhen
China	Shenzhen university General Hospital	Shenzhen
China	Tianjin Medical University General Hospital	Tianjin
China	Weifang People's Hospital	Weifang
China	The First Affiliated Hospital of Xian Jiaotong University	XI An
China	Yantai Yuhuangding Hospital	Yantai
China	Daping Hospital Army Characteristic Medical Center	Yuzhong District
China	Henan Cancer Hospital	Zhengzhou
Czechia	Fakultni nemocnice Olomouc - I.P.Pavlova 6	Olomouc
Czechia	Vitkovicka nemocnice a.s.	Ostrava- Vitkovice
Czechia	Fakultni nemocnice Plzen	Plzen
Denmark	Rigshospitalet	Copenhagen
France	Institut Sainte Catherine	Avignon Cedex 9
France	Hospices Civils de Lyon HCL	Bron
France	CHU de Grenoble Hopital Albert Michallon	La Tronche
France	Centre Hospitalier du Mans	le Mans
France	CHR Hôpital Calmette	Lille
France	Hopital Nord	Marseille Cedex 20
France	CHU de Montpellier - Arnaud de Villeneuve	Montpellier Cedex 5
France	Institut Curie	Paris
France	CHU Bordeaux	Pessac
France	CHRU Hopital de Pontchaillou	Rennes
France	CHU Nantes	Sain-Herblain
France	Nouvel Hopital Civil - CHU Strasbourg	Strasbourg cedex
France	CHU Bretonneau	Tours
Germany	Evangelische Lungenklinik Berlin	Berlin
Germany	Asklepios Klinikum Harburg	Hamburg
Germany	Thoraxklinik am Universitatsklinikum Heidelberg	Heidelberg
Germany	Onkologische Schwerpunktpraxis	Heilbronn
Germany	POIS Sachsen GmbH iG	Leipzig
Germany	Bethanien Krankenhaus	Moers
Germany	Klinikum der Universitaet Muenchen	München
Germany	Oncologianova GmbH	Recklinghausen
Germany	Universitaetsklinikum Regensburg	Regensburg
Hong Kong	Queen Mary Hospital	Hong Kong
India	Health Care Global Enterprises pvt Ltd	Bangalore
India	Artemis Hospital	Gurugram
India	Tata Medical Center	Kolkata
India	Tata Memorial Hospital	Mumbai
India	HCG Manavta Cancer Centre	Nasik
India	Rajiv Gandhi Cancer Institute and Research Centre	New Delh
India	Noble Hospital Pvt Ltd	Pune
India	Bhaktivedanta Hospital & Research Institute	Thane
Israel	Soroka University Medical Center	Beersheba
Israel	Rambam Health Corporation	Haifa
Israel	Shaare Zedek 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	CRO IRCCS Istituto Nazionale Tumori	Aviano
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola
Italy	Istituto Europeo di Oncologia	Milano
Italy	Azienda Ospedaliero-Universitaria Di Parma	Parma
Italy	Ospedale S. Maria Delle Croci	Ravenna
Italy	Istituto Nazionale Tumori Regina Elena	Roma
Italy	Policlinico G.B.Rossi	Verona
Japan	National Hospital Organization Shibukawa Medical Center	Gunma
Japan	Hyogo Cancer Center	Hyogo
Japan	Kanagawa Cancer Center	Kanagawa
Japan	Kobe City Medical Center General Hospital	Kobe City
Japan	Kurume University Hospital	Kurume
Japan	National Hospital Organization Nagoya Medical Center	Nagoya-shi
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Osaka International Cancer Institute	Osaka City
Japan	Shizuoka Cancer Center	Shizuoka
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital	Tokyo
Japan	Ehime University Hospital	Toon-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	CHA Bundang Medical Center, CHA University	Gyeonggi-do
Korea, Republic of	National Cancer Center	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-do
Korea, Republic of	GyeongSang National University Hospital	Gyeongsangnam-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam 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	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Hospital Tengku Ampuan Afzan	Kuantan
Malaysia	Beacon Hospital Sdn Bhd	Petaling Jaya
Malaysia	Subang Jaya Medical Centre	Subang Jaya
Malaysia	Mount Miriam Cancer Hospital	Tanjung Bungah
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	Oncologia Integral Satelite	Naucalpan
Netherlands	VUMC Amsterdam	Amsterdam
Netherlands	Ziekenhuis St Jansdal	Harderwijk
Netherlands	Erasmus MC	Rotterdam
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	Wielkopolskie Centrum Pulmonologii i Torakochirurgii im. Eugenii i Janusza Zeylandow	Poznan
Poland	Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy	Warszawa
Portugal	Centro Hospitalar Lisboa Norte EPE - Hospital Pulido Valente	Lisboa
Portugal	Hospital Beatriz Angelo	Loures
Portugal	Centro Hospitalar Universitario do Porto, EPE	Porto
Portugal	Instituto Portugues de Oncologia	Porto
Puerto Rico	Pan American Center for Oncology Trials LLC	Rio Piedras
Russian Federation	City Clinical Hospital #1	Nalchik
Russian Federation	Llc, Eurocityclinic	Saint Petersburg
Spain	Hosp. Univ. A Coruna	A Coruña
Spain	Hosp Clinic de Barcelona	Barcelona
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. Insular de Gran Canaria	Las Palmas de Gran Canaria
Spain	Hosp Univ Fund Jimenez Diaz	Madrid
Spain	Hosp. Gral. Univ. Gregorio Maranon	Madrid
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Univ. Hm Sanchinarro	Madrid
Spain	Hosp. Univ. La Paz	Madrid
Spain	Hosp. Univ. Pta. de Hierro Majadahonda	Majadahonda
Spain	Hosp. Regional Univ. de Malaga	Málaga
Spain	Clinica Univ. de Navarra	Pamplona
Spain	Hosp. Virgen Del Rocio	Seville
Spain	Hosp. Gral. Univ. Valencia	Valencia
Spain	Hosp. Univ. I Politecni La Fe	Valencia
Sweden	Sahlgrenska Universitetssjukhuset	Goteborg
Sweden	Linkoping University Hospital	Linkoping
Sweden	Skanes universitetssjukhus	Lund
Sweden	Norrlands Universitetssjukhus	Umea
Sweden	Akademiska Sjukhuset	Uppsala
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Taipei Medical University Shuang Ho Hospital	New Taipei City
Taiwan	Chung Shan Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Turkey	Adana City Hospital	Adana
Turkey	Ankara Bilkent City Hospital	Ankara
Turkey	Gazi University Hospital	Ankara
Turkey	Memorial Ankara Hastanesi	Ankara
Turkey	Trakya University Medical Faculty	Edirne
Turkey	Bakirkoy Training and Research Hospital	Istanbul
Turkey	Goztepe Prof Dr Suleyman Yalcin Sehir Hastanesi	Istanbul
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Medipol Mega University Hospital	Istanbul
Turkey	Medical Point	Izmir
United Kingdom	Velindre Hospital	Cardiff
United Kingdom	Edinburgh Cancer Centre Western General	Edinburgh
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London
United Kingdom	The Royal Marsden NHS Trust	London
United Kingdom	UCL Cancer Institute	London
United Kingdom	The Christie Nhs Foundation Trust	Manchester
United States	University Cancer And Blood Center LLC	Athens	Georgia
United States	University of Vermont Medical Center	Burlington	Vermont
United States	University of Virginia	Charlottesville	Virginia
United States	TriHealth Network	Cincinnati	Ohio
United States	Rocky Mountain Cancer Centers	Colorado Springs	Colorado
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Texas Oncology-Medical City Dallas	Dallas	Texas
United States	City of Hope	Duarte	California
United States	Astera Cancer Care	East Brunswick	New Jersey
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Holy Cross Hospital - Michael and Dianne Bienes Comprehensive Cancer Center	Fort Lauderdale	Florida
United States	Nebraska Cancer Specialists	Grand Island	Nebraska
United States	Texas Oncology	Grapevine	Texas
United States	Alliance Cancer Specialists	Horsham	Pennsylvania
United States	Oncology Consultants - Texas	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Texas Oncology - Northeast	Longview	Texas
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Baptist Cancer Center	Memphis	Tennessee
United States	Southern Cancer Center, PC	Mobile	Alabama
United States	University of California Irvine	Orange	California
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	NorthWest Medical Specialties, PLLC	Puyallup	Washington
United States	Arizona Oncology Associates	Tucson	Arizona
United States	Compass Oncology	Vancouver	Washington
United States	Blue Ridge Cancer Care	Wytheville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Czechia,  Denmark,  France,  Germany,  Hong Kong,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  Poland,  Portugal,  Puerto Rico,  Russian Federation,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) According to RECIST v1.1 Guidelines as Assessed by Blinded Independent Central Review (BICR)	PFS is defined as the time from randomization until the date of objective disease progression or death, whichever comes first, using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	Up to approximately 28 months
Secondary	Objective Response as Assessed by BICR	Objective response is defined as the percentage of participants who achieve either a complete response (CR) or partial response (PR) as their best response as defined by BICR using RECIST v1.1 criteria.	Up to approximately 28 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 48 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.	Up to approximately 28 months
Secondary	Time to Subsequent Therapy (TTST)	TTST is defined as the time from the date of randomization to the start date of the subsequent anti-cancer therapy following study treatment discontinuation, or death whichever comes first.	Up to approximately 28 months
Secondary	Progression-Free Survival After First Subsequent Therapy (PFS2)	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 28 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 or death.	Up to approximately 28 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 28 months
Secondary	Intracranial Objective Response Rate (ORR) as Assessed by BICR	Intracranial ORR is defined as the percentage of participants who achieve either an intracranial CR or PR, as defined by BICR using RECIST v1.1.	Up to approximately 28 months
Secondary	Intracranial Duration of Response (DOR) as Assessed by BICR	Intracranial DoR is defined as the time from the date of first documented intracranial response (PR or CR) until the date of documented intracranial progression or death, whichever comes first, for participants who have intracranial CR or PR.	Up to approximately 28 months
Secondary	Time to Intracranial Disease Progression as Assessed by BICR	Time to intracranial disease progression is defined as the time from randomization until the date of objective intracranial disease progression, based on BICR using RECIST v1.1.	Up to approximately 28 months
Secondary	Number of Participants with Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.	Up to'approximately 48 months
Secondary	Number of Participants with Clinical Laboratory Abnormalities	Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, blood coagulation, and urinalysis) will be reported.	Up to approximately 48 months
Secondary	Serum Concentration of Amivantamab	Serum samples will be analyzed to determine concentrations of amivantamab.	Up to approximately 28 months
Secondary	Plasma Concentration of Lazertinib	Plasma samples will be analyzed to determine concentrations of lazertinib.	Up to approximately 28 months
Secondary	Number of Participants with Anti-Amivantamab Antibodies	Number of participants with anti-amivantamab antibodies will be reported.	Up to approximately 28 months
Secondary	Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ)	NSCLC-SAQ is a 7-item PRO measure designed for use in adults to assess symptoms of advanced non-small cell lung cancer (NSCLC). The NSCLC-SAQ has a seven-day recall period. It contains five domains and accompanying items that will be identified as symptoms of NSCLC: cough (1 item), pain (2 items), dyspnea (1 item), fatigue (2 items), and appetite (1 item). Each item uses a response scale between 0 to 4, with higher scores indicating more severe symptomatology. All five of these domains must be non-missing to compute a total score, with a response range from 0 to 20 with higher scores indicating more severe symptomatology.	Up to approximately 28 months
Secondary	European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Score	The EORTC QLQ-C30 includes 30 items in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single symptom items. The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.	Up to approximately 28 months
Secondary	Patient Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF)	PROMIS-PF is used to characterize and better understand overall health, level of physical disability, and general well-being. Physical function is a foundation for commonly used general and cancer-specific patient reported outcomes (PRO) measures.	Up to approximately 28 months