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

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.

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).

Study Overview

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

Detailed 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).

• Study Type: Interventional
• Enrollment (Actual): 1074
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1428ANZ
    • Instituto Alexander Fleming
  • Buenos Aires, Argentina, C1426AGE
    • Centro Oncologico Korben
  • Córdoba, Argentina, X5016KEH
    • Hospital Privado Centro Médico de Córdoba
  • La Rioja, Argentina, F5300COE
    • Centro Oncologico Riojano Integral (CORI)
  • Viedma, Argentina, R8500ACE
    • Clínica Viedma
• Australia
  • Bedford Park, Australia, 5042
    • Flinders Medical Centre
  • Heidelberg, Australia, 3084
    • Austin Hospital
  • Malvern, Australia, 3144
    • Cabrini Medical Centre
  • Murdoch, Australia, 6150
    • St John of God Hospital Murdoch
  • Nedlands, Australia, 6009
    • Sir Charles Gairdner Hospital
  • Westmead, Australia, 2145
    • Westmead Hospital
  • Wollongong, Australia, 2500
    • Southern Medical Day Care Centre
  • Woolloongabba, Australia, 4102
    • Princess Alexandra Hospital
• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint Luc
  • Charleroi, Belgium, 6060
    • Grand Hopital De Charleroi Site Les Viviers
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Ottignies, Belgium, 1340
    • Clinique Saint Pierre
  • Roeselare, Belgium, 8800
    • Algemeen Ziekenhuis Delta
• Brazil
  • Barretos, Brazil, 14784-400
    • Fundação Pio XII
  • Belo Horizonte, Brazil, 30110-022
    • Cetus Oncologia
  • Florianópolis, Brazil, 88020-210
    • Ynova Pesquisa Clinica
  • Ijuí, Brazil, 98700-000
    • ONCOSITE - Centro de Pesquisa Clinica em Oncologia LTDA
  • Natal, Brazil, 59062 000
    • Liga Norte Riograndense Contra O Cancer
  • Pelotas, Brazil, 96020 080
    • UPCO Unidade de Pesquisa Clinica em Oncologia
  • Porto Alegre, Brazil, 90020-090
    • Irmandade Santa Casa de Misericordia de Porto Alegre
  • Porto Alegre, Brazil, 90610-000
    • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS
  • Rio de Janeiro, Brazil, 22 250 905
    • Oncoclinicas Rio de Janeiro S A
  • Rio de Janeiro, Brazil, 22281 100
    • Instituto D Or de Pesquisa e Ensino IDOR
  • Rio de Janeiro, Brazil, 20231 050
    • Ministerio da Saude Instituto Nacional do Cancer
  • Sorocaba, Brazil, 18030-075
    • IOS - Instituto de Oncologia de Sorocaba Dr. Gilson Delgado
  • São Paulo, Brazil, 04014-002
    • Núcleo de Pesquisa São Camilo
  • São Paulo, Brazil, 01509 900
    • Fundacao Antonio Prudente A C Camargo Cancer Center
  • São Paulo, Brazil, 01246 000
    • Fundacao Faculdade de Medicina Instituto do Cancer do Estado de Sao Paulo
  • Vitória, Brazil, 29308-014
    • Hospital Evangelico de Cachoeiro de Itapemirim
• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • William Osler Health System
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
• China
  • Beijing, China, 101149
    • Beijing Chest Hospital, Capital Medical University
  • Beijing, China, 100853
    • Chinese PLA General Hospital
  • Beijing, China, 100050
    • Beijing Friendship Hospital Capital Medical University
  • Beijing, China, 100142
    • Beijing Cancer Hospital Respiratory Medicine Department II
  • Beijing, China, 100142
    • Beijing Cancer Hospital Respiratory Medicine Department I
  • Changchun, China, 130000
    • Jilin Cancer Hospital
  • Changsha, China, 410013
    • Hunan Cancer hospital Thoracic Medicine Department II
  • Changsha, China, 410013
    • Hunan Cancer hospital Thoracic Medicine Department I
  • Changzhou, China, 213003
    • The First People's Hospital of Changzhou
  • Chengdu, China, 610041
    • Sichuan Cancer Hospital
  • Chengdu, China, 610041
    • West China Hospital Sichuan University
  • Chongqing, China, 400038
    • Southwest Hospital
  • 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
  • Nantong, China, 226300
    • Nantong Tumor Hospital
  • Shanghai, China, 200030
    • Shanghai Chest Hospital
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center
  • Shanghai, China, 200123
    • Shanghai East Hospital
  • Shanghai, China, 200025
    • Ruijin Hospital Shanghai Jiao Tong University
  • Shenyang, China, 110022
    • Shengjing Hospital of China Medical University
  • Tianjin, China, 300052
    • Tianjin Medical University General Hospital
  • Wenzhou, China, 325000
    • The First Affiliated Hospital of Wenzhou Medical University
  • Wuhan, China, 430030
    • TongJi Hospital of TongJi Medical College of Huazhong University of Science & Technology
  • Xi'an, China, 710061
    • The First Affiliated Hospital of Xiân Jiaotong University
  • Yantai, China, 264000
    • Yantai Yuhuangding Hospital
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital
  • Ürümqi, China, 830000
    • Cancer Hospital of Xinjiang Medical University
• France
  • Bordeaux, France, 33000
    • Institut Bergonie
  • Bron, France, 69500
    • Hospices Civils de Lyon HCL
  • La Tronche, France, 38700
    • CHU de Grenoble Hopital Albert Michallon
  • Lille, France, 59000
    • Institute Coeur Poumon
  • Limoges, France, 87000
    • CHU de Limoges
  • Marseille, France, 13915
    • Hopital Nord
  • Paris, France, 75970
    • Hopital Tenon
  • Paris, France, 75005
    • Institut Curie
  • Pessac, France, 33604
    • CHU Bordeaux
  • Sain-Herblain, France, 44800
    • CHU Nantes
  • Saint-Mandé, France, 94163
    • Hia Begin
  • Tours, France, 37000
    • CHU Bretonneau
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Bad Berka, Germany, 99437
    • Zentralklinik Bad Berka GmbH
  • Berlin, Germany, 14165
    • Helios Klinikum Emil von Behring GmbH
  • Cologne, Germany, 51109
    • Kliniken Der Stadt Koeln Ggmbh
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen
  • Gauting, Germany, 82131
    • Asklepios Klinik Gauting GmbH - Asklepios Fachkliniken Munchen-Gauting
  • Halle, Germany, 06120
    • Städtisches Krankenhaus Martha-Maria Halle-Dölau gGmbH
  • Heidelberg, Germany, 69126
    • Thoraxklinik am Universitatsklinikum Heidelberg
  • Heilbronn, Germany, 74072
    • Onkologische Schwerpunktpraxis
  • Leipzig, Germany, 04357
    • POIS Leipzig GbR
  • Oldenburg, Germany, 26121
    • Pius-Hospital Oldenburg
  • Stuttgart, Germany, 70376
    • Robert-Bosch-Krankenhaus - Klinik Schillerhoehe
• Hungary
  • Budapest, Hungary, H-1529
    • Orszagos Koranyi Tbc es Pulmonologiai Intezet
  • Farkasgyepü, Hungary, 8582
    • Veszprém Megyei Tudőgyógyintézet
  • Gyöngyös, Hungary, 3233
    • Mátrai Gyógyintézet-Bronchológia
  • Szombathely, Hungary, 9700
    • Markusovszky Egyetemi Oktatókórház
  • Székesfehérvár, Hungary, 8000
    • Fejer Varmegyei Szent Gyorgy Egyetemi Oktatokorhaz
  • Törökbálint, Hungary, 2045
    • Tudogyogyintezet Torokbalint
• India
  • Hyderabad, India, 500034
    • Basavatarakam Indo-American Hospital
  • Kolkata, India, 700160
    • Tata Medical Center
  • Mumbai, India, 400012
    • Tata Memorial Hospital
  • Nashik, India, 422002
    • HCG Manavta Cancer Centre
  • Pune, India, 411013
    • Noble Hospital Pvt Ltd
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Corporation
  • Jerusalem, Israel, 9112001
    • Hadassah 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
  • Avellino, Italy, 83100
    • Ospedale San Giuseppe Moscati di Avellino
  • Catania, Italy, 95123
    • Azienda Ospedaliero Univ. Policlinico Gaspare Rodolico
  • Meldola, Italy, 47014
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milan, Italy, 20141
    • Istituto Europeo di Oncologia
  • Milan, Italy, 20122
    • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
  • Milan, Italy, 20132
    • IRCCS Ospedale San Raffaele
  • Monza, Italy, 20052
    • San Gerardo Hospital
  • Naples, Italy, 80100
    • Ospedale Monaldi
  • Orbassano, Italy, 10043
    • AOU San Luigi Gonzaga
  • Ravenna, Italy, 48121
    • Ospedale S. Maria delle Croci
  • Roma, Italy, 00168
    • Irccs Gemelli
  • Rozzano, Italy, 20089
    • Istituto Clinico Humanitas
• Japan
  • Bunkyō City, Japan, 113 8431
    • Juntendo University Hospital
  • Chūōku, Japan, 104 0045
    • National Cancer Center Hospital
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center
  • Himeji, Japan, 670-8520
    • National Hospital Organization Himeji Medical Center
  • Hirakata, Japan, 573 1191
    • Kansai Medical University Hospital
  • Kanazawa, Japan, 920 8641
    • Kanazawa University Hospital
  • Kashiwa, Japan, 277 8577
    • National Cancer Center Hospital East
  • Kurume, Japan, 830-0011
    • Kurume University Hospital
  • Matsusaka, Japan, 515-8544
    • Matsusaka Municipal Hospital
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Okayama, Japan, 700 8558
    • Okayama University Hospital
  • Osaka Sayama Shi, Japan, 589 8511
    • Kindai University Hospital
  • Shibukawa, Japan, 377-0280
    • National Hospital Organization Shibukawa Medical Center
  • Tokyo, Japan, 135 8550
    • The Cancer Institute Hospital of Jfcr
  • Tokyo, Japan, 152 8902
    • National Hospital Organization Tokyo Medical Center
  • Toon-shi, Japan, 791-0295
    • Ehime University Hospital
  • Toyonaka-shi, Japan, 560-8552
    • National Hospital Organization Osaka Toneyama Medical Center
  • 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
  • George Town, Malaysia, 10990
    • Hospital Pulau Pinang
  • Johor Bahru, Malaysia, 81100
    • Hospital Sultan Ismail
  • Kuala Lumpur, Malaysia, 50586
    • Hospital Kuala Lumpur
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Centre
  • Kuantan, Malaysia, 25100
    • Hospital Tengku Ampuan Afzan
  • Petaling Jaya, Malaysia, 46050
    • Beacon Hospital Sdn Bhd
• Mexico
  • Guadalajara, Mexico, 44280
    • Hospital Civil de Guadalajara Fray Antonio Alcalde
  • León, Mexico, 37000
    • CIMOVA, Morals Vargas Centro de Investigación SC
  • Mexico City, Mexico, 14050
    • Médica Sur
  • Mexico City, Mexico, 03100
    • Mexico Centre for Clinical Research, S.A. de C.V.
  • Monterrey, Mexico, 64710
    • I Can Oncology Center
  • México, Mexico, 03100
    • Health Pharma Professional Research
  • México, Mexico, 14080
    • Instituto Nacional de Cancerologia
  • Naucalpan, Mexico, 53100
    • Oncología Integral Satélite
• Netherlands
  • 's-Hertogenbosch, Netherlands, 5223 GZ
    • Jeroen Bosch Ziekenhuis
  • Arnhem, Netherlands, 6815 AD
    • Rijnstate Ziekenhuis
  • Harderwijk, Netherlands, 3844 DG
    • Ziekenhuis St Jansdal
  • Nijmegen, Netherlands, 6525AG
    • UMC Radboud
• Poland
  • Bydgoszcz, Poland, 85 796
    • Centrum Onkologii im Prof F Lukaszczyka
  • Gdansk, Poland, 80 214
    • 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
  • 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
  • Porto, Portugal, 4200-072
    • Instituto Portugues de Oncologia
  • Porto, Portugal, 4099-001
    • Uls Santo Antonio - Hosp. Santo Antonio
  • Porto, Portugal, 4100 180
    • Hosp. Cuf Porto
• Puerto Rico
  • Rio Piedras, Puerto Rico, 00935
    • Pan American Center for Oncology Trials LLC
• Russia
  • Irkutsk, Russia, 664035
    • Irkutsk Regional Oncology Dispensary
  • Krasnogorsk, Russia, 143423
    • Moscow City Oncology Hospital № 62
  • Krasnoyarsk, Russia, 660133
    • Krasnoyarsk Regional Oncology Dispensary
  • Kuzmolovsky, Russia, 188663
    • Leningrad Regional Oncology Dispensary
  • Moscow, Russia, 115533
    • MCK
  • Nal'chik, Russia, 360000
    • City Clinical Hospital #1
  • Nizhny Novgorod, Russia, 603000
    • Nizhny Novgorod Regional Oncological Dispensary
  • Omsk, Russia, 664013
    • Omsk Clinical Oncology Dispensary
  • Saint Petersburg, Russia, 197758
    • N.N. Petrov Research Institute Of Oncology
  • Saint Petersburg, Russia, 196006
    • Oncology Medical Clinics AV Medical group
  • Saint Petersburg, Russia, 190121
    • Current medical technologies
  • Tambov, Russia, 392013
    • Tambov Regional Oncology Clinical Dispansary
  • Tomsk, Russia, 634050
    • Tomsk Cancer Research Institute
  • Ufa, Russia, 450083
    • Bashkir State Medical University
  • Yaroslavl, Russia, 150054
    • Yaroslavl Regional Clinical Oncology Hospital
• South Korea
  • Busan, South Korea, 48108
    • Inje university Haeundae Paik Hospital
  • Cheongju-si, South Korea, 28644
    • Chungbuk National University Hospital
  • Seongnam-si, South Korea, 13620
    • Seoul National University Bundang 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, 03181
    • Kangbuk Samsung Hospital
  • Seoul, South Korea, 06591
    • The Catholic University of Korea Seoul St Mary s Hospital
  • Seoul, South Korea, 8308
    • Korea University Guro Hospital
• Spain
  • A Coruña, Spain, 15006
    • Hosp Univ A Coruna
  • Badalona, Spain, 08916
    • Inst. Cat. D'Oncologia-Badalona
  • Barcelona, Spain, 08025
    • Hosp. de La Santa Creu I Sant Pau
  • Barcelona, Spain, 08028
    • Hosp. Univ. Quiron Dexeus
  • Barcelona, Spain, 08035
    • Hosp Univ Vall D Hebron
  • Burgos, Spain, 09003
    • Hosp. Univ. de Burgos
  • Girona, Spain, 17007
    • Institut Catala D'Oncologia Girona
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28046
    • Hosp. Univ. La Paz
  • Madrid, Spain, 28007
    • Hosp. Gral. Univ. Gregorio Maranon
  • Majadahonda, Spain, 28222
    • Hosp. Univ. Pta. de Hierro Majadahonda
  • Málaga, Spain, 29011
    • 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
  • Zaragoza, Spain, 50009
    • Hosp. Clinico Univ. Lozano Blesa
• Taiwan
  • Kaohsiung City, Taiwan, 824
    • E-DA Hospital
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Chung Ho Memorial Hospital
  • Kaohsiung City, Taiwan, 833
    • Chang Gung Medical Foundation
  • New Taipei City, Taiwan, 23561
    • Taipei Medical University Shuang Ho Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taichung, Taiwan, 402
    • Chung Shan Medical University Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
  • Bangkok, Thailand, 10400
    • Phramongkutklao Hospital and Medical College
  • Chiang Mai, Thailand, 50200
    • Chiang Mai University
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital, Prince of Songkla University
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01060
    • Adana City Hospital
  • Adana, Turkey (Türkiye), 01250
    • Başkent University Medical Faculty Adana Application and Research Center
  • Ankara, Turkey (Türkiye), 6800
    • Ankara Bilkent City Hospital
  • Ankara, Turkey (Türkiye), 06560
    • Gazi Hastanesi
  • Edirne, Turkey (Türkiye), 22030
    • Trakya University Medical Faculty
  • Istanbul, Turkey (Türkiye), 34098
    • Istanbul Universitesi Cerrahpasa Tip Fakultesi Ic Hastaliklari Anabilim Dali Medikal Onkoloji Bd
  • Istanbul, Turkey (Türkiye), 34722
    • T C Saglik Bakanlıgi Goztepe Prof Dr Suleyman Yalcın Sehir Hastanesi
  • Istanbul, Turkey (Türkiye), 34214
    • Medipol Mega University Hospital
  • Izmir, Turkey (Türkiye), 35575
    • Medical Point
  • Konya, Turkey (Türkiye), 42080
    • Necmettin Erbakan University Meram Medical Faculty
• Ukraine
  • Dnipro, Ukraine, 49102
    • Dnipropetrovsk State Medical Academy, Dnipropetrovsk City Multifield Clinical Hospital # 4
  • Kharkiv, Ukraine, 61070
    • Municipal non-profit enterprise 'Regional Center of Oncology'
  • Kyiv, Ukraine, 02091
    • Medical Center 'Ok Clinic' of LLC 'International Institute of Clinical Studies'
  • Kyiv, Ukraine, 03022
    • State Nonprofit Enterprise National Cancer Institute
  • Uzhhorod, Ukraine, 88000
    • Municipal Oncology Centre of Uzhgorod Central Municipal Clinical Hospitlal
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Edinburgh Cancer Centre Western General
  • London, United Kingdom, SW10 9NH
    • Chelsea and Westminster Hospital
  • London, United Kingdom, NW1 2PG
    • UCL Cancer Institute
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Trust
  • Manchester, United Kingdom, M20 4BX
    • Christie NHS Foundation Trust
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals NHS Trust
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden NHS Trust 1
• United States
  • Arizona
    • Goodyear, Arizona, United States, 85395
      • Arizona Oncology Associates, PC - HAL
    • Yuma, Arizona, United States, 85364
      • Yuma Regional Medical Center
  • California
    • Long Beach, California, United States, 90813
      • City of Hope Long Beach Elm
    • Orange, California, United States, 92868
      • University of California Irvine
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Cancer Centers
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Cancer Specialists of North Florida
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer and Blood Center LLC
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • East Jefferson General Hospital
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Maryland Oncology Hematology, PA
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Minnesota Oncology Hematology P A
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Astera Cancer Care
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Institute and Research Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Austin, Texas, United States, 78745
      • Texas Oncology P A
    • Houston, Texas, United States, 77030
      • Oncology Consultants Texas
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists

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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm A (Open-label): Amivantamab and Lazertinib; Participants will receive amivantamab 1050 milligram (mg) intravenously (IV) for body weight less than (<) 80 kilogram (kg) and 1400 mg for body weight greater than or equal to (>=) 80 kg in 28-day cycles: once weekly in Cycle 1 (with a split dose on Days 1-2), and then every 2 weeks in subsequent cycles. Lazertinib will be administered 240 mg (80*3) orally once daily.	Drug: Amivantamab; Participants will receive amivantamab intravenously.; Other Names: JNJ-61186372; Drug: Lazertinib; Participants will receive lazertinib tablets orally.; Other Names: JNJ-73841937 and YH-25448
Active Comparator: Treatment Arm B (Double-blind): Osimertinib+Placebo Lazertinib; Participants will receive osimertinib 80 mg orally once daily plus matching placebo of lazertinib 240 mg (80*3) orally once daily.	Drug: Placebo; Participants will receive matching placebo orally.; Drug: Osimertinib; Participants will receive osimertinib capsules orally.
Experimental: Treatment Arm C (Double-blind): Lazertinib+Placebo Osimertinib; Participants will receive lazertinib 240 mg (80*3) orally once daily plus matching placebo of osimertinib 80 mg orally once daily.	Drug: Placebo; Participants will receive matching placebo orally.; Drug: Lazertinib; Participants will receive lazertinib tablets orally.; Other Names: JNJ-73841937 and YH-25448

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 was defined as the time from randomization until the date of objective disease progression based on BICR using RECIST version 1.1 or death (by any cause) the absence of progression, whichever came first. Disease progression was defined using RECIST 1.1 as a 20 percent (%) increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 millimeters (mL). Participants who have not progressed or have not died at the time of analysis were censored at the time of the latest date of their last evaluable RECIST version 1.1 assessment.	From randomization to either disease progression or death whichever occurs first (up to 32.8 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Approximately 60 months (time from the date of randomization until the date of death due to any cause)
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.	Approximately 32.8 months
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.	Approximately 32.8 months
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.	Approximately 60 months
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.	Approximately 60 months
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.	Approximately 60 months
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.	Approximately 60 months
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.	Approximately 60 months
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.	Approximately 60 months
Number of Participants With Physical Examination Abnormalities	Number of participants with physical examination abnormalities will be reported.	Approximately 60 months
Serum Concentration of Amivantamab	Serum samples will be analyzed to determine concentrations of Amivantamab.	Approximately 60 months
Plasma Concentration of Lazertinib	Plasma samples will be analyzed to determine concentrations of Lazertinib.	Approximately 60 months
Number of Participants With Anti-Amivantamab Antibodies	Number of participants with antibodies to amivantamab will be reported.	Approximately 60 months
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 60 months
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 60 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Cho BC, Felip E, Hayashi H, Thomas M, Lu S, Besse B, Sun T, Martinez M, Sethi SN, Shreeve SM, Spira AI. MARIPOSA: phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small-cell lung cancer. Future Oncol. 2022 Feb;18(6):639-647. doi: 10.2217/fon-2021-0923. Epub 2021 Dec 16.
• Cho BC, Lu S, Felip E, Spira AI, Girard N, Lee JS, Lee SH, Ostapenko Y, Danchaivijitr P, Liu B, Alip A, Korbenfeld E, Mourao Dias J, Besse B, Lee KH, Xiong H, How SH, Cheng Y, Chang GC, Yoshioka H, Yang JC, Thomas M, Nguyen D, Ou SI, Mukhedkar S, Prabhash K, D'Arcangelo M, Alatorre-Alexander J, Vazquez Limon JC, Alves S, Stroyakovskiy D, Peregudova M, Sendur MAN, Yazici O, Califano R, Gutierrez Calderon V, de Marinis F, Passaro A, Kim SW, Gadgeel SM, Xie J, Sun T, Martinez M, Ennis M, Fennema E, Daksh M, Millington D, Leconte I, Iwasawa R, Lorenzini P, Baig M, Shah S, Bauml JM, Shreeve SM, Sethi S, Knoblauch RE, Hayashi H; MARIPOSA Investigators. Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC. N Engl J Med. 2024 Oct 24;391(16):1486-1498. doi: 10.1056/NEJMoa2403614. Epub 2024 Jun 26.
• Yang JC, Lu S, Hayashi H, Felip E, Spira AI, Girard N, Kim YJ, Lee SH, Ostapenko Y, Danchaivijitr P, Liu B, Alip A, Korbenfeld E, Mourao Dias J, Besse B, Passaro A, Lee KH, Xiong H, How SH, Cheng Y, Chang GC, Yoshioka H, Thomas M, Nguyen D, Ou SI, Mukhedkar S, Prabhash K, D'Arcangelo M, Alatorre-Alexander J, Vazquez Limon JC, Alves S, Stroyakovskiy D, Peregudova M, Sendur MAN, Yazici O, Califano R, Gutierrez Calderon V, de Marinis F, Kim SW, Gadgeel SM, Owen S, Xie J, Sun T, Mehta J, Venkatasubramanian R, Ennis M, Fennema E, Daksh M, Roshak A, Man J, Knoblauch RE, Bauml JM, Baig M, Shah S, Sethi S, Cho BC; MARIPOSA Investigators. Overall Survival with Amivantamab-Lazertinib in EGFR-Mutated Advanced NSCLC. N Engl J Med. 2025 Oct 30;393(17):1681-1693. doi: 10.1056/NEJMoa2503001. Epub 2025 Sep 7.
• Lee SH, Lu S, Hayashi H, Felip E, Spira AI, Girard N, Kim YJ, Ostapenko Y, Danchaivijitr P, Liu B, Alip A, Korbenfeld E, Dias JM, Lee KH, Xiong H, How SH, Cheng Y, Chang GC, Chih-Hsin Yang J, Besse B, Thomas M, Shah S, Baig M, Curtin JC, Zhang J, Xie J, Sun T, Sethi S, Wang M, Fennema E, Daksh M, Ennis M, Bauml JM, Cho BC. Lazertinib Versus Osimertinib in Previously Untreated EGFR-Mutant Advanced NSCLC: A Randomized, Double-Blind, Exploratory Analysis From MARIPOSA. J Thorac Oncol. 2025 Nov;20(11):1655-1668. doi: 10.1016/j.jtho.2025.06.030. Epub 2025 Jul 3.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2020
• Primary Completion (Actual): August 11, 2023
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: July 23, 2020
• First Submitted That Met QC Criteria: July 23, 2020
• First Posted (Actual): July 27, 2020

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; Substandard Drugs; Pharmaceutical Preparations; amivantamab; lazertinib; osimertinib
• Other Study ID Numbers: CR108856; 2020-000743-31 (EudraCT Number); 73841937NSC3003 (Other Identifier: Janssen Research & Development, LLC); 2023-506576-27-00 (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 Johnson & Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/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