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
  • Cordoba, Argentina, X5016KEH
    • Hospital Privado Centro Medico de Cordoba
  • La Rioja, Argentina, F5300COE
    • Centro Oncologico Riojano Integral (CORI)
  • Viedma, Argentina, R8500ACE
    • Clinica 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
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint Luc
  • Charleroi, Belgium, 6000
    • Grand Hopital de Charleroi, site Notre Dame
  • 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
  • Florianopolis, Brazil, 88020-210
    • YNOVA Pesquisa Clinica
  • Ijui, Brazil, 98700-000
    • ONCOSITE - Centro de Pesquisa Clinica em Oncologia Ltda
  • Natal, Brazil, 59062 000
    • Liga Norte Riograndense Contra O Câncer
  • Pelotas, Brazil, 96020 080
    • UPCO Unidade de Pesquisa Clinica em Oncologia
  • Porto Alegre, Brazil, 90610-000
    • Uniao Brasileira de Educaçao e Assistencia-Hospital Sao Lucas da PUCRS
  • Porto Alegre, Brazil, 90020-090
    • Irmandade Santa Casa de Misericordia de Porto Alegre
  • Rio De Janeiro, Brazil, 20231-050
    • Ministerio da Saude - Instituto Nacional do Cancer
  • 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)
  • Sao Paulo, Brazil, 01246-000
    • Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo
  • Sao Paulo, Brazil, 04014-002
    • Núcleo de Pesquisa São Camilo
  • Sao Paulo, Brazil, 01509 900
    • Fundacao Antonio Prudente A C Camargo Cancer Center
  • Sorocaba, Brazil, 18030-075
    • IOS - Instituto de Oncologia de Sorocaba Dr. Gilson Delgado
  • Vitoria, 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, 100142
    • Beijing Cancer Hospital
  • Beijing, China, 100853
    • Chinese PLA General Hospital
  • Beijing, China, 101199
    • Beijing Chest Hospital, Capital Medical University
  • Beijing, China, 100050
    • Beijing Friendship Hospital Capital Medical University
  • Changchun, China, 130000
    • Jilin Cancer Hospital
  • Changsha, China, 410013
    • HuNan Cancer Hospital
  • 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
  • Guang Zhou, China, 510080
    • The First Affiliated Hospital, Sun Yat-sen University
  • Guangzhou, China, 510120
    • Sun Yat-sen Memorial Hospital Sun Yat-sen University
  • Hang Zhou, China, 310022
    • Zhejiang Cancer Hospital
  • Hangzhou, China, 310016
    • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
  • Hangzhou, China, 310009
    • Second Affiliated Hospital, School of Medicine, Zhejiang University
  • Hangzhou, China, 310009
    • The Second Affiliated Hospital of Zhejiang University College 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, 200025
    • Ruijin Hospital, Shanghai Jiao Tong University
  • Shanghai, China, 200123
    • Shanghai East Hospital
  • Shenyang, China, 110022
    • Shengjing Hospital of China Medical University
  • Tianjin, China, 300052
    • Tianjin Medical University General Hospital
  • Urumchi, China, 830000
    • Cancer Hospital of Xinjiang Medical University
  • 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 Xian Jiaotong University
  • Yantai, China, 264000
    • Yantai Yuhuangding Hospital
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital
• 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 Cedex 20, 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 Mande, France, 94163
    • Hia Begin
  • Tours, France, 37000
    • CHU Bretonneau
  • Villejuif Cedex, France, 94805
    • Institut Gustave Roussy
• Germany
  • Bad Berka, Germany, 99437
    • Zentralklinik Bad Berka GmbH
  • Berlin, Germany, 14165
    • Helios Klinikum Emil von Behring GmbH
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen
  • Gauting, Germany, 82131
    • Asklepios Klinik Gauting GmbH - Asklepios Fachkliniken München-Gauting
  • Halle (Saale), Germany, 06120
    • Städtisches Krankenhaus Martha-Maria Halle-Dölau gGmbH
  • Heidelberg, Germany, 69126
    • Thoraxklinik am Universitätsklinikum Heidelberg
  • Heilbronn, Germany, 74072
    • Onkologische Schwerpunktpraxis
  • Koeln, Germany, 51109
    • Kliniken der Stadt Koeln gGmbH
  • 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
    • Veszprem Megyei Tudogyogyintezet
  • Gyöngyös, Hungary, 3233
    • Mátrai Gyógyintézet-Bronchológia
  • Szekesfehervar, Hungary, 8000
    • Fejer Varmegyei Szent Gyorgy Egyetemi Oktatokorhaz
  • Szombathely, Hungary, 9700
    • Markusovszky Egyetemi Oktatokorhaz
  • Torokbalint, Hungary, 2045
    • Tudogyogyintezet Torokbalint
• India
  • Hyderabad, India, 500034
    • Basavatarakam Indo-American Hospital
  • Kolkata, India, 700160
    • Tata Medical Center
  • Mumbai, India, 400012
    • Tata Memorial Hospital
  • Nasik, 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
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milano, Italy, 20132
    • IRCCS Ospedale San Raffaele
  • Milano, Italy, 20141
    • Istituto Europeo di Oncologia
  • Milano, Italy, 20122
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • Monza, Italy, 20052
    • San Gerardo Hospital
  • Napoli, 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
  • Bunkyo-Ku, Japan, 113-8431
    • Juntendo University Hospital
  • Chuo-Ku, 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, 152-8902
    • National Hospital Organization Tokyo Medical Center
  • Tokyo, Japan, 135 8550
    • The Cancer Institute Hospital of JFCR
  • 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
• Korea, Republic of
  • Busan, Korea, Republic of, 48108
    • Inje University Haeundae Paik Hospital
  • Cheongju-si, Korea, Republic of, 28644
    • Chungbuk National University Hospital
  • Seongnam-si, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03181
    • Kangbuk Samsung Hospital
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea Seoul St. Mary'S Hospital
  • Seoul, Korea, Republic of, 8308
    • Korea University Guro Hospital
• 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
  • Ciudad de Mexico, Mexico, 03100
    • Mexico Centre for Clinical Research, S.A. de C.V.
  • Ciudad de Mexico, Mexico, 14050
    • Médica Sur
  • Guadalajara, Mexico, 44280
    • Hospital Civil de Guadalajara Fray Antonio Alcalde
  • Leon, Mexico, 37000
    • CIMOVA, Morals Vargas Centro de Investigación SC
  • Mexico, Mexico, 03100
    • Health Pharma Professional Research
  • Mexico, Mexico, 14080
    • Instituto Nacional de Cancerologia
  • Monterrey, Mexico, 64710
    • i Can Oncology Center
  • Naucalpan, Mexico, 53100
    • Oncologia Integral Satelite
• Netherlands
  • Arnhem, Netherlands, 6815 AD
    • Rijnstate ziekenhuis
  • Harderwijk, Netherlands, 3844 DG
    • Ziekenhuis St Jansdal
  • Nijmegen, Netherlands, 6525AG
    • UMC Radboud
  • s-Hertogenbosch, Netherlands, 5223 GZ
    • Jeroen Bosch Ziekenhuis
• Poland
  • Bydgoszcz, Poland, 85-796
    • Centrum Onkologii im. Prof. F. Lukaszczyka
  • Gdańsk, 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
  • Warszawa, Poland, 02-781
    • Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
• Portugal
  • Lisboa, Portugal, 1769-001
    • Centro Hospitalar Lisboa Norte EPE - Hospital Pulido Valente
  • Porto, Portugal, 4099-001
    • Centro Hospitalar Universitário Do Porto, Epe
  • Porto, Portugal, 4200-072
    • Instituto Português de Oncologia
  • Porto, Portugal, 4100 180
    • Hospital Cuf porto
• Puerto Rico
  • Rio Piedras, Puerto Rico, 00935
    • Pan American Center for Oncology Trials LLC
• Russian Federation
  • Irkutsk, Russian Federation, 664035
    • Irkutsk Regional Oncology Dispensary
  • Krasnogorsk, Russian Federation, 143423
    • Moscow City Oncology Hospital № 62
  • Krasnoyarsk, Russian Federation, 660133
    • Krasnoyarsk Regional Oncology Dispensary
  • Kuzmolovsky, Russian Federation, 188663
    • Leningrad Regional Oncology Dispensary
  • Moscow, Russian Federation, 115533
    • MCK
  • Nalchik, Russian Federation, 360000
    • City Clinical Hospital #1
  • Nizhniy Novgorod, Russian Federation, 603000
    • Nizhny Novgorod Regional Oncological Dispensary
  • Omsk, Russian Federation, 664013
    • Omsk Clinical Oncology Dispensary
  • Saint Petersburg, Russian Federation, 190121
    • Current medical technologies
  • Saint Petersburg, Russian Federation, 197758
    • N.N. Petrov Research Institute of Oncology
  • St-Petersburg, Russian Federation, 196006
    • Oncology Medical Clinics AV Medical group
  • Tambov, Russian Federation, 392013
    • Tambov Regional Oncology Clinical Dispansary
  • Tomsk, Russian Federation, 634050
    • Tomsk Cancer Research Institute
  • Ufa, Russian Federation, 450083
    • Bashkir State Medical University
  • Yaroslavl, Russian Federation, 150054
    • Yaroslavl Regional Clinical Oncology Hospital
• Spain
  • A Coruña, Spain, 15006
    • Hosp. Univ. A Coruna
  • Badalona, Spain, 08916
    • Inst. Cat. D'Oncologia-Badalona
  • Barcelona, Spain, 08035
    • Hosp. Univ. Vall D Hebron
  • Barcelona, Spain, 08025
    • Hosp. de La Santa Creu I Sant Pau
  • Barcelona, Spain, 08028
    • Hosp. Univ. Quiron Dexeus
  • 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
  • Malaga, 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, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Kaohsiung, Taiwan, 824
    • E-DA hospital
  • Kaohsiung, Taiwan, 833
    • Chang Gung Medical Foundation
  • New Taipei, 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 City, Taiwan, 10002
    • National Taiwan University Hospital
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
  • Bangkok, Thailand, 10400
    • Phramongkutklao Hospital and Medical College
  • Chiangmai, Thailand, 50200
    • Chiang Mai University
  • Songkla, Thailand, 90110
    • Songklanagarind Hospital, Prince of Songkla University
• Turkey
  • Adana, Turkey, 01060
    • Adana City Hospital
  • Adana, Turkey, 01250
    • Başkent University Medical Faculty Adana Application and Research Center
  • Ankara, Turkey, 6560
    • Gazi University Hospital
  • Ankara, Turkey, 6800
    • Ankara Bilkent City Hospital
  • Edirne, Turkey, 22030
    • Trakya University Medical Faculty
  • Istanbul, Turkey, 34098
    • Istanbul Universitesi Cerrahpasa Tip Fakultesi Ic Hastaliklari Anabilim Dali Medikal Onkoloji Bd
  • Istanbul, Turkey, 34214
    • Medipol Mega University Hospital
  • Istanbul, Turkey, 34722
    • T.C. Saglik Bakanlıgi Goztepe Prof. Dr. Suleyman Yalcın Sehir Hastanesi
  • Izmir, Turkey, 35575
    • Medical Point
  • Konya, Turkey, 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
    • National Cancer Institute
  • Uzhgorod, 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
• 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 & 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
    • Saint 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 RECIST v1.1 by Blinded Independent Central Review (BICR)	PFS is defined as the time from randomization until the date of objective disease progression or death, whichever occurred first, based on BICR using response evaluation criteria in solid tumors (RECIST) v1.1.	Up to approximately 42 months

Secondary 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.	Up to 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.	Up to approximately 42 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.	Up to approximately 42 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.	Up to approximately 42 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.	Up to approximately 42 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.	Up to approximately 42 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.	Up to 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.	Up to 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.	Up to approximately 60 months
Number of Participants with Physical Examination Abnormalities	Number of participants with physical examination abnormalities will be reported.	Up to approximately 60 months
Serum Concentration of Amivantamab	Serum samples will be analyzed to determine concentrations of amivantamab.	Up to approximately 42 months
Plasma Concentration of Lazertinib	Plasma samples will be analyzed to determine concentrations of lazertinib.	Up to approximately 42 months
Number of Participants with Anti-Amivantamab Antibodies	Number of participants with antibodies to amivantamab will be reported.	Up to approximately 42 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 42 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 42 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2020
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): June 9, 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): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Osimertinib; Amivantamab-vmjw; Lazertinib
• Other Study ID Numbers: CR108856; 2020-000743-31 (EudraCT Number); 73841937NSC3003 (Other Identifier: Janssen Research & Development, LLC)

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