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 (MARIPOSA-2)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Lazertinib; Drug: Amivantamab; Drug: Pemetrexed; Drug: Carboplatin

Detailed Description

Lung cancer is one of the most common types of cancer and is the most common cause of death from cancer. NSCLC accounts for approximately 85 percent (%) of lung cancers. Advanced NSCLC is a serious terminal illness that accounts for approximately 20% of all cancer mortality, and until recently had a median overall survival (OS) of approximately 1 year. Amivantamab (JNJ-61186372) is a low fucose, fully human immunoglobulin (IgG)1-based bispecific antibody directed against EGFR and mesenchymal-epithelial transition (MET) tyrosine kinase receptors. It shows clinical activity against tumors with primary activating EGFR mutations Exon 19del and Exon 21 L858R substitution. Lazertinib (JNJ-73841937; YH-25448) is an oral, highly potent, third-generation EGFR tyrosine kinase inhibitor (TKI). It selectively inhibits both primary activating EGFR mutations (Exon 19del, Exon 21 L858R substitution) and the EGFR T790M resistance mutation, with less inhibition of wild-type EGFR. The study consists of a Screening Phase (up to 28 days), a Treatment Phase (from randomization until the End of Treatment visit) and a Follow-up Phase (from End of Treatment Visit until the end of study, death, lost to follow-up, or withdrawal of consent, whichever comes first). Safety will be assessed by physical examinations, laboratory tests, vital signs, electrocardiograms, Eastern Cooperative Oncology Group (ECOG) performance status, and monitoring of adverse events (AEs). The total duration of the study is up to 48 months.

• Study Type: Interventional
• Enrollment (Actual): 776
• Phase: Phase 3

Expanded Access

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Contacts and Locations

Study Locations

• Argentina
  • CABA, Argentina, C1122
    • IADT Instituto Argentino de Diagnostico y Tratamiento
  • CABA, Argentina, C1414
    • Centro Medico Fleischer
  • CABA, Argentina, C1431FWO
    • CEMIC (Centro de Educación Médica e Investigaciones Clínicas)
  • Caba, Argentina, C1027AAP
    • CINME Centro de Investigaciones Metabolicas
  • Córdoba, Argentina, X5016KEH
    • Hospital Privado Universitario De Cordoba
  • Córdoba, Argentina, 5000
    • Cemaic Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica
  • Mar del Plata, Argentina, B7602CBM
    • Hospital Privado de la Comunidad
  • Viedma, Argentina, R8500ACE
    • Clinica Viedma
• Belgium
  • Charleroi, Belgium, 6060
    • Grand Hopital De Charleroi Site Les Viviers
  • Edegem, Belgium, 2650
    • UZA
  • Ghent, Belgium, 9000
    • UZ Gent
  • Hasselt, Belgium, 3500
    • Jessa Ziekenhuis - Campus Virga Jesse
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Liège, Belgium, 4000
    • CHU Sart-Tilman
  • Ottignies, Belgium, 1340
    • Clinique Saint Pierre
• Brazil
  • Belo Horizonte, Brazil, 30110-017
    • Cetus Oncologia
  • Curitiba, Brazil, 80810 050
    • CIONC Centro Integrado de Oncologia de Curitiba
  • Florianópolis, Brazil, 88020-210
    • Ynova Pesquisa Clinica
  • Ipatinga, Brazil, 35162 189
    • Fundacao Sao Francisco Xavier
  • Pelotas, Brazil, 96020 080
    • UPCO Unidade de Pesquisa Clinica em Oncologia
  • Porto Alegre, Brazil, 90160-093
    • Hospital Ernesto Dornelles
  • Porto Alegre, Brazil, 90035-001
    • Associacao Hospitalar Moinhos de Vento
  • Rio de Janeiro, Brazil, 22250-905
    • Oncoclinicas Rio de Janeiro S A
  • Rio de Janeiro, Brazil, 22281 100
    • Instituto D Or de Pesquisa e Ensino IDOR
  • Rio de Janeiro, Brazil, 22775 001
    • Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)
  • Salvador, Brazil, 40170 110
    • Nucleo de Oncologia da Bahia
  • Salvador, Brazil, 41253 190
    • Hospital Sao Rafael
  • Santo André, Brazil, 09060 650
    • CEPHO Centro de Estudos e Pesquisa de Hematologia e Oncologia
  • Sorocaba, Brazil, 18030-005
    • IOS - Instituto de Oncologia de Sorocaba Dr. Gilson Delgado
  • São Paulo, Brazil, 01409902
    • Hospital Nove de Julho
  • São Paulo, Brazil, 04543-000
    • Onco Star Sp Oncologia Ltda
  • São Paulo, Brazil, 01509 900
    • Fundacao Antonio Prudente A C Camargo Cancer Center
  • São Paulo, Brazil, 01323-000
    • Hospital Paulistano
  • São Paulo, Brazil, 01323 900
    • Real e Benemerita Associacao Portuguesa de Beneficencia
  • São Paulo, Brazil, 01327 001
    • Hospital Alemao Oswaldo Cruz
  • Uberlândia, Brazil, 38408-150
    • COT - Centro Oncologico do Triangulo S.A
• Bulgaria
  • Sofia, Bulgaria, 1407
    • Multiprofile Hospital for Active Treatment 'Tokuda Hospital Sofia'
  • Sofia, Bulgaria, 1756
    • Specialized Hospital for Active Treatment in Oncology
  • Sofia, Bulgaria, 1797
    • UMHAT Sofia Med
  • Sofia, Bulgaria, 1303
    • Multifunctional Hospital for Active Treatment 'Serdika'
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Arthur J E Child Comprehensive Cancer Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • British Columbia Cancer Agency
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China, 100853
    • Chinese PLA General Hospital
  • Beijing, China, 100044
    • Peking University People's Hospital
  • Beijing, China, 100021
    • Cancer hospital, Chinese Academy of Medical Sciences
  • Beijing, China, 101199
    • Beijing Chest Hospital, Capital Medical University
  • Beijing, China, 100142
    • Beijing Cancer Hospital Chest Tumor Internal Medicine dept. II
  • Changsha, China, 410013
    • Hunan Cancer Hospital
  • Changsha, China, 410013
    • Hunan Cancer Hospital Chest Tumor Internal Medicine dept. II
  • Chengdu, China, 610041
    • Sichuan Cancer Hospital
  • Chengdu, China, 610041
    • West China Hospital Sichuan University
  • Chongqing, China, 400038
    • Southwest Hospital
  • Chongqing, China, 400000
    • Chongqing University Cancer Hospital
  • Chongqing, China, 400042
    • Daping Hospital Army Characteristic Medical Center
  • Guangzhou, China, 510120
    • Sun Yat-Sen Memorial Hospital Sun Yat-sen University
  • Guangzhou, China, 510080
    • The First Affiliated Hospital Sun Yat sen University
  • Hangzhou, China, 310022
    • Zhejiang Cancer Hospital
  • Hangzhou, China, 310009
    • Second Affiliated Hospital, School of Medicine, Zhejiang University
  • Hangzhou, China, 310009
    • The Second Affiliated Hospital of Zhejiang University College of Medicine
  • Hangzhou, China, 310016
    • Sir Run Run Shaw Hospital Zhejiang University School of Medicine
  • Harbin, China, 150000
    • Harbin medical university cancer hospital
  • Huizhou, China, 516001
    • Huizhou Municipal Central Hospital
  • Linhai, China, 317000
    • Taizhou Hospital of Zhejiang Province
  • Nanchong, China, 637503
    • Affiliated Hospital of North Sichuan Medical College
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center
  • Shanghai, China, 310000
    • Shanghai East Hospital
  • Shanghai, China, 200025
    • Ruijin Hospital Shanghai Jiao Tong University
  • Shenzhen, China, 518055
    • Shenzhen University General Hospital
  • Shenzhen, China, 518116
    • Cancer Hospital Chinese Academy of Medical Sciences
  • Tianjin, China, 300052
    • Tianjin Medical University General Hospital
  • Weifang, China, 261000
    • Weifang People's Hospital
  • Xi'an, China, 710061
    • The First Affiliated Hospital of Xian Jiaotong University
  • Yantai, China, 264000
    • Yantai Yuhuangding Hospital
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital
• Czechia
  • Olomouc, Czechia, 775 20
    • Fakultni nemocnice Olomouc - I.P.Pavlova 6
  • Ostrava- Vitkovice, Czechia, 70300
    • Vitkovicka nemocnice a.s.
  • Pilsen, Czechia, 30599
    • Fakultni nemocnice Plzen
• Denmark
  • Copenhagen, Denmark, DK 2100
    • Rigshospitalet
• France
  • Avignon, France, 84918
    • Institut Sainte Catherine
  • Bron, France, 69500
    • Hospices Civils de Lyon HCL
  • La Tronche, France, 38700
    • CHU de Grenoble Hopital Albert Michallon
  • Le Mans, France, 72000
    • Centre Hospitalier du Mans
  • Lille, France, 59000
    • CHR Hôpital Calmette
  • Marseille, France, 13915
    • Hopital Nord
  • Montpellier, France, 34295
    • CHU de Montpellier - Arnaud de Villeneuve
  • Paris, France, 75005
    • Institut Curie
  • Pessac, France, 33604
    • CHU Bordeaux
  • Rennes, France, 35033
    • CHRU Hopital de Pontchaillou
  • Sain-Herblain, France, 44800
    • CHU Nantes
  • Strasbourg, France, 67091
    • Nouvel Hopital Civil - CHU Strasbourg
  • Tours, France, 37000
    • Chu Bretonneau
• Germany
  • Berlin, Germany, 13125
    • Evangelische Lungenklinik Berlin
  • Hamburg, Germany, 21075
    • Asklepios Klinikum Harburg
  • Heidelberg, Germany, 69126
    • Thoraxklinik am Universitatsklinikum Heidelberg
  • Heilbronn, Germany, 74072
    • Onkologische Schwerpunktpraxis
  • Leipzig, Germany, 04357
    • POIS Sachsen GmbH iG
  • Moers, Germany, 47441
    • Bethanien Krankenhaus
  • München, Germany, 80336
    • Klinikum der Universitaet Muenchen
  • Recklinghausen, Germany, 45659
    • Oncologianova GmbH
  • Regensburg, Germany, 93053
    • Universitaetsklinikum Regensburg
• Hong Kong
  • Hong Kong, Hong Kong, 999077
    • Queen Mary Hospital
• India
  • Bangalore, India, 560027
    • Health Care Global Enterprises pvt Ltd
  • Gurugram, India, 122001
    • Artemis Hospital
  • Kolkata, India, 700160
    • Tata Medical Center
  • Mumbai, India, 400012
    • Tata Memorial Hospital
  • Nashik, India, 422002
    • HCG Manavta Cancer Centre
  • New Delh, India, 110085
    • Rajiv Gandhi Cancer Institute and Research Centre
  • Pune, India, 411013
    • Noble Hospital Pvt Ltd
  • Thane, India, 411107
    • Bhaktivedanta Hospital & Research Institute
• Israel
  • Beersheba, Israel, 84101
    • Soroka University Medical Center
  • Haifa, Israel, 3109601
    • Rambam Health Corporation
  • Jerusalem, Israel, 91031
    • Shaare Zedek Medical Center
  • Kfar Saba, Israel, 44281
    • Meir Medical Center
  • Petah Tikva, Israel, 49100
    • Rabin Medical Center
  • Ramat Gan, Israel, 5262100
    • Chaim Sheba Medical Center
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center
• Italy
  • Aviano, Italy, 33081
    • CRO IRCCS Istituto Nazionale Tumori
  • Meldola, Italy, 47014
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Milan, Italy, 20141
    • Istituto Europeo di Oncologia
  • Parma, Italy, 43126
    • Azienda Ospedaliero-Universitaria Di Parma
  • Ravenna, Italy, 48121
    • Ospedale S. Maria Delle Croci
  • Roma, Italy, 00144
    • Istituto Nazionale Tumori Regina Elena
  • Verona, Italy, 37134
    • Policlinico G.B.Rossi
• Japan
  • Gunma, Japan, 377-0280
    • National Hospital Organization Shibukawa Medical Center
  • Hyōgo, Japan, 673-8558
    • Hyogo Cancer Center
  • Kanagawa, Japan, 241-8515
    • Kanagawa Cancer Center
  • Kobe, Japan, 650 0047
    • Kobe City Medical Center General Hospital
  • Kurume, Japan, 830-0011
    • Kurume University Hospital
  • Nagoya, Japan, 460-0001
    • National Hospital Organization Nagoya Medical Center
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Osaka, Japan, 541 8567
    • Osaka International Cancer Institute
  • Shizuoka, Japan, 411 8777
    • Shizuoka Cancer Center
  • Tokyo, Japan, 135 8550
    • The Cancer Institute Hospital of JFCR
  • Tokyo, Japan, 113 8677
    • Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
  • Toon-shi, Japan, 791-0295
    • Ehime University Hospital
  • Wakayama, Japan, 641 8510
    • Wakayama Medical University Hospital
  • Yamaguchi, Japan, 740-8510
    • National Hospital Organization Iwakuni Clinical Center
  • Yamaguchi, Japan, 755-0241
    • National Hospital Organization Yamaguchi Ube Medical Center
• Malaysia
  • Kuala Lumpur, Malaysia
    • University Malaya Medical Centre
  • Kuantan, Malaysia, 25100
    • Hospital Tengku Ampuan Afzan
  • Petaling Jaya, Malaysia, 46050
    • Beacon Hospital Sdn Bhd
  • Subang Jaya, Malaysia, 47500
    • Subang Jaya Medical Centre
  • Tanjung Bungah, Malaysia, 11200
    • Mount Miriam Cancer Hospital
• Mexico
  • Guadalajara, Mexico, 44280
    • Hospital Civil de Guadalajara Fray Antonio Alcalde
  • León, Mexico, 37000
    • CIMOVA, Morals Vargas Centro de Investigación SC
  • México, Mexico, 03100
    • Health Pharma Professional Research
  • México, Mexico, 14080
    • Instituto Nacional de Cancerologia
  • Naucalpan, Mexico, 53100
    • Oncologia Integral Satelite
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VUMC Amsterdam
  • Harderwijk, Netherlands, 3844 DG
    • Ziekenhuis St Jansdal
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus MC
• Poland
  • Bydgoszcz, Poland, 85 796
    • Centrum Onkologii im Prof F Lukaszczyka
  • Gdansk, Poland, 80 952
    • Uniwersyteckie Centrum Kliniczne
  • Gdynia, Poland, 81 519
    • Szpitale Pomorskie Sp z o o
  • Olsztyn, Poland, 10-357
    • Warminsko-Mazurskie Centrum Chorob Pluc w Olsztynie
  • Poznan, Poland, 60-693
    • Private Specialist Hospitals - MedPolonia
  • Poznan, Poland, 60 569
    • Wielkopolskie Centrum Pulmonologii i Torakochirurgii im. Eugenii i Janusza Zeylandow
  • Warsaw, Poland, 02-781
    • Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
• Portugal
  • Lisbon, Portugal, 1769-001
    • Uls Santa Maria - Hosp. Pulido Valente
  • Loures, Portugal, 2674 514
    • Uls Loures Odivelas - Hosp. Loures
  • Porto, Portugal, 4200072
    • Instituto Portugues de Oncologia
  • Porto, Portugal, 4099-001
    • Uls Santo Antonio - Hosp. Santo Antonio
• Puerto Rico
  • Rio Piedras, Puerto Rico, 00917
    • Pan American Center for Oncology Trials LLC
• Russia
  • Nal'chik, Russia, 360000
    • City Clinical Hospital #1
  • Saint Petersburg, Russia, 197022
    • Llc, Eurocityclinic
• South Korea
  • Gyeonggi-do, South Korea, 13496
    • CHA Bundang Medical Center, CHA University
  • Gyeonggi-do, South Korea, 13620
    • Seoul National University Bundang Hospital
  • Gyeonggi-do, South Korea, 10408
    • National Cancer Center
  • Gyeongsangnam-do, South Korea, 52727
    • Gyeongsang National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital Yonsei University Health System
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 02841
    • Korea University Anam Hospital
  • Seoul, South Korea, 06591
    • The Catholic University of Korea Seoul St Mary s Hospital
• Spain
  • A Coruña, Spain, 15006
    • Hosp Univ A Coruna
  • Barcelona, Spain, 08025
    • Hosp. de La Santa Creu I Sant Pau
  • Barcelona, Spain, 08028
    • Hosp. Univ. Quiron Dexeus
  • Barcelona, Spain, 08036
    • Hosp Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hosp Univ Vall D Hebron
  • Las Palmas de Gran Canaria, Spain, 35016
    • Hosp. Univ. Insular de Gran Canaria
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28046
    • Hosp. Univ. La Paz
  • Madrid, Spain, 28007
    • Hosp. Gral. Univ. Gregorio Maranon
  • Madrid, Spain, 28040
    • Hosp Univ Fund Jimenez Diaz
  • Madrid, Spain, 28050
    • Hosp Univ Hm Sanchinarro
  • Majadahonda, Spain, 28222
    • Hosp. Univ. Pta. de Hierro Majadahonda
  • Málaga, Spain, 29010
    • Hosp Regional Univ de Malaga
  • Pamplona, Spain, 31008
    • Clinica Univ. de Navarra
  • Seville, Spain, 41013
    • Hosp. Virgen Del Rocio
  • Valencia, Spain, 46014
    • Hosp. Gral. Univ. Valencia
  • Valencia, Spain, 46026
    • Hosp. Univ. I Politecni La Fe
• Sweden
  • Gothenburg, Sweden, 413 45
    • Sahlgrenska Universitetssjukhuset
  • Linköping, Sweden, 581 85
    • Linkoping University Hospital
  • Lund, Sweden, 221 85
    • Skanes universitetssjukhus
  • Umeå, Sweden, 901 85
    • Norrlands Universitetssjukhus
  • Uppsala, Sweden, 75181
    • Akademiska Sjukhuset
• Taiwan
  • Changhua, Taiwan, 500
    • Changhua Christian Hospital
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Chung Ho Memorial Hospital
  • New Taipei City, Taiwan, 23561
    • Taipei Medical University Shuang Ho Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taichung, Taiwan, 402
    • Chung Shan Medical University Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01060
    • Adana City Hospital
  • Ankara, Turkey (Türkiye), 06800
    • Ankara Bilkent City Hospital
  • Ankara, Turkey (Türkiye), 06520
    • Memorial Ankara Hastanesi
  • Ankara, Turkey (Türkiye), 06560
    • Gazi University Hospital
  • Edirne, Turkey (Türkiye), 22030
    • Trakya University Medical Faculty
  • Istanbul, Turkey (Türkiye), 34722
    • Goztepe Prof Dr Suleyman Yalcin Sehir Hastanesi
  • Istanbul, Turkey (Türkiye), 34098
    • Istanbul University Cerrahpasa Medical Faculty
  • Istanbul, Turkey (Türkiye), 34147
    • Bakirkoy Training and Research Hospital
  • Istanbul, Turkey (Türkiye), 34214
    • Medipol Mega University Hospital
  • Izmir, Turkey (Türkiye), 35575
    • Medical Point
• United Kingdom
  • Cardiff, United Kingdom, CF14 2TL
    • Velindre Hospital
  • Edinburgh, United Kingdom, EH4 2XU
    • Edinburgh Cancer Centre Western General
  • London, United Kingdom, NW1 2PG
    • UCL Cancer Institute
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Trust
  • London, United Kingdom, SE1 9RT
    • Guys and St Thomas NHS Foundation Trust
  • Manchester, United Kingdom, M20 4BX
    • The Christie Nhs Foundation Trust
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Southern Cancer Center, PC
  • Arizona
    • Tucson, Arizona, United States, 85711
      • Arizona Oncology Associates
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Orange, California, United States, 92868
      • University of California Irvine
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Rocky Mountain Cancer Centers
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital - Michael and Dianne Bienes Comprehensive Cancer Center
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer and Blood Center LLC
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Nebraska Cancer Specialists
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Astera Cancer Care
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • TriHealth Network
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Northwest
  • Pennsylvania
    • Horsham, Pennsylvania, United States, 19044
      • Alliance Cancer Specialists
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Baptist Cancer Center
  • Texas
    • Dallas, Texas, United States, 75230
      • Texas Oncology-Medical City Dallas
    • Dallas, Texas, United States, 75246
      • Texas Oncology Baylor Charles A Sammons Cancer Center
    • Grapevine, Texas, United States, 76051
      • Texas Oncology
    • Houston, Texas, United States, 77030
      • Oncology Consultants Texas
    • Longview, Texas, United States, 75601
      • Texas Oncology - Northeast
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
    • Wytheville, Virginia, United States, 24382
      • Blue Ridge Cancer Care
  • Washington
    • Puyallup, Washington, United States, 98373
      • NorthWest Medical Specialties, PLLC
    • Vancouver, Washington, United States, 98684
      • Compass Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm B: CP (Carboplatin and Pemetrexed); Participants will receive Pemetrexed in combination with Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Pemetrexed as maintenance until disease progression.	Drug: Pemetrexed; Pemetrexed will be administered as an IV infusion.; Drug: Carboplatin; Carboplatin will be administered as an IV infusion.
Experimental: Arm C: ACP (Amivantamab, Carboplatin and Pemetrexed); Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.	Drug: Amivantamab; Amivantamab will be administered as an IV infusion.; Other Names: JNJ-61186372; Drug: Pemetrexed; Pemetrexed will be administered as an IV infusion.; Drug: Carboplatin; Carboplatin will be administered as an IV infusion.
Experimental: Arm C2 (Extension Cohort): ACP; Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.	Drug: Amivantamab; Amivantamab will be administered as an IV infusion.; Other Names: JNJ-61186372; Drug: Pemetrexed; Pemetrexed will be administered as an IV infusion.; Drug: Carboplatin; Carboplatin will be administered as an IV infusion.
Experimental: Arm A: LACP/ACP-L; LACP dosing (study start until 6 November 2022): Participants will receive Lazertinib orally along with Amivantamab, Pemetrexed, and Carboplatin as IV infusion starting on Cycle 1 Day 1 for 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression. ACP-L dosing (from 7 November 2022 until study completion): Participants will receive Amivantamab, Pemetrexed, and Carboplatin starting on Cycle 1 Day 1 for 4 cycles. Lazertinib in ACP-L will start on Cycle 5 Day 1 or sooner if carboplatin is discontinued before cycle 4 (each cycle consists of 21 days). Beginning with Cycle 5 Day 1, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression.	Drug: Lazertinib; Lazertinib will be administered orally.; Other Names: JNJ-73841937; YH-25448; Drug: Amivantamab; Amivantamab will be administered as an IV infusion.; Other Names: JNJ-61186372; Drug: Pemetrexed; Pemetrexed will be administered as an IV infusion.; Drug: Carboplatin; Carboplatin will be administered as an IV infusion.
Experimental: Arm A2 (Extension Cohort): ACP-L; Participants will receive Amivantamab, Pemetrexed and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days), Lazertinib will start on C5D1 or sooner if carboplatin is discontinued earlier). After 4 cycles, participants will receive Pemetrexed, Amivantamab, Lazertinib as maintenance until disease progression.	Drug: Lazertinib; Lazertinib will be administered orally.; Other Names: JNJ-73841937; YH-25448; Drug: Amivantamab; Amivantamab will be administered as an IV infusion.; Other Names: JNJ-61186372; Drug: Pemetrexed; Pemetrexed will be administered as an IV infusion.; Drug: Carboplatin; Carboplatin will be administered as an IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Main Study: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 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 came first, as assessed by BICR according to RECIST version 1.1. Progressed disease: Sum of diameters increased by greater than or equal to (>=)20 percent (%) and >=5 millimeter (mm) from nadir (including baseline if it was smallest sum).	From randomization to either disease progression or death, whichever occurred first (up to 1 year 7 months)
Main Study + Extension Cohort: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	Follow-up for the extension cohort is still ongoing and thus results from the analysis that includes the extension cohort will be reported up on study completion.	up to 4 years 10 months
Main Study + Extension Cohort: Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review		Up to 4 years 10 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Main Study+ Extension Cohort: Objective Response Rate as Assessed by Blinded Independent Central Review	Up to 4 years 10 months
Main Study+ Extension Cohort: Overall Survival	Up to 4 years 10 months
Main Study+ Extension Cohort: Duration of Response as Assessed by Blinded Independent Central Review	Up to 4 years 10 months
Main Study+ Extension Cohort: Time to Subsequent Therapy	Up to 4 years 10 months
Main Study+ Extension Cohort: Progression-free Survival (PFS) After First Subsequent Therapy (PFS2)	Up to 4 years 10 months
Main Study+ Extension Cohort: Time to Symptomatic Progression	Up to 4 years 10 months
Main Study+ Extension Cohort: Intracranial Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review	Up to 4 years 10 months
Main Study: Number of Participants With Adverse Events (AEs)	Up to 4 years 10 months
Main Study+ Extension Cohort: Number of Participants With Adverse Events (AEs) by Severity	Up to 4 years 10 months
Main Study+ Extension Cohort: Number of Participants With Clinical Laboratory Abnormalities	Up to 4 years 10 months
Main Study+ Extension Cohort: Serum Concentration of Amivantamab	Up to 4 years 10 months
Main Study+ Extension Cohort: Plasma Concentration of Lazertinib	Up to 4 years 10 months
Main Study + Extension Cohort: Number of Participants With Serum Anti-amivantamab Antibodies	Up to 4 years 10 months
Main Study+ Extension Cohort: Change From Baseline With Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ)	Up to 4 years 10 months
Main Study+ Extension Cohort: Change From Baseline With European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)	Up to 4 years 10 months
Main Study+ Extension Cohort: Change From Baseline With Patient-Reported Outcomes Measurement Information System -Physical Function (PROMIS-PF)	Up to 4 years 10 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2021
• Primary Completion (Actual): July 10, 2023
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: July 30, 2021
• First Submitted That Met QC Criteria: July 30, 2021
• First Posted (Actual): August 3, 2021

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Pemetrexed; Carboplatin; amivantamab; lazertinib
• Other Study ID Numbers: CR109061; 2021-001825-33 (EudraCT Number); 61186372NSC3002 (Other Identifier: Janssen Research & Development, LLC); 2023-506518-33-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at www.janssen.com/clinical trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No