A Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non-small Cell Lung Cancer
PALOMA-3
A Phase 3, Open-label, Randomized Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Patients With EGFR-mutated Advanced or Metastatic Non-small Cell Lung Cancer After Progression on Osimertinib and Chemotherapy
4 other identifiers
interventional
418
20 countries
187
Brief Summary
The purpose of the study is to simplify amivantamab intravenous administration and to reduce dose times, by assessing a new formulation of amivantamab, amivantamab subcutaneous and co-formulated with recombinant human hyaluronidase (SC-CF), for subcutaneous administration. This formulation has the potential to enhance both the patient and physician experience with amivantamab by providing easier and accelerated administration.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Aug 2022
Longer than P75 for phase_3
187 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 19, 2022
CompletedFirst Posted
Study publicly available on registry
May 24, 2022
CompletedStudy Start
First participant enrolled
August 5, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 3, 2024
CompletedResults Posted
Study results publicly available
February 2, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
June 30, 2027
ExpectedApril 13, 2026
April 1, 2026
1.4 years
May 19, 2022
January 15, 2026
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
For All Regions Other Than the European Union (EU) and Others Accepting Cycle 2 Day 1: Observed Serum Concentration (Ctrough) of Amivantamab at Steady State
Ctrough was the observed serum concentration of Amivantamab at steady state immediately prior to the next drug administration.
Pre-dose on Cycle 4 Day 1 (each cycle of 28 days)
For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab
Ctrough was the observed serum concentration of Amivantamab immediately prior to the next drug administration.
Pre-dose on Cycle 2 Day 1 (each cycle of 28 days)
Area Under the Concentration (AUC) Time Curve of Amivantamab From Day 1 to Day 15 (AUC [Day 1-15]) of Cycle 2
AUC (Day 1-15) defined as area under the concentration time curve from Cycle 2 Day 1 to Day 15 were reported.
Cycle 2: Arm A: pre-dose, 24, 48, 72, 96, 168, and 360 hours (hrs) post-dose on Day 1; Arm B: pre-infusion, end of infusion (EOI)+10 minutes, EOI+2, EOI+6, EOI+24, EOI+48, EOI+72, EOI+168, and EOI+360 hrs post dose on Day 1
Secondary Outcomes (20)
Objective Response Rate (ORR)
Up to 3 years 4 months
Progression-Free Survival (PFS)
Up to 3 years 4 months
Duration of Response (DOR)
Up to 3 years 4 months
Time to Response (TTR)
Up to 3 years 4 months
Number of Participants With Adverse Events (AEs)
Up to 3 years 4 months
- +15 more secondary outcomes
Study Arms (2)
Arm A: Lazertinib with Amivantamab SC-CF
EXPERIMENTALLazertinib 240 milligrams (mg) will be administered orally once daily. Participants will receive amivantamab subcutaneous and co-formulated with recombinant human hyaluronidase (SC-CF), 1600 mg/ 2240 mg depending on the body weight by manual injection. Participants benefiting from study treatment after primary analysis may continue to receive access to study treatment within the study by transferring to the long-term extension (LTE) Phase.
Arm B: Lazertinib with Amivantamab Intravenous (IV) Infusion
EXPERIMENTALLazertinib 240 mg will be administered orally once. Participants will receive amivantamab, 1050 mg or 1400 mg depending on the body weight as an IV infusion. Participants benefiting from study treatment after primary analysis may continue to receive access to study treatment within the study by transferring to the LTE Phase.
Interventions
Amivantamab will be administered by IV infusion.
Lazertinib tablets will be administered orally.
Amivantamab injection will be administered subcutaneously by manual injection.
Eligibility Criteria
You may qualify if:
- Have histologically or cytologically confirmed, advanced or metastatic non-small cell lung cancer (NSCLC), characterized by either epidermal growth factor receptor (EGFR) Exon 19 deletion (Exon 19del) or Exon 21 leucine 858 to arginine substitution (Exon 21 L858R) mutation by an Food and Drug Administration (FDA)-approved or other validated test of either circulating tumor deoxyribonucleic acid (ctDNA) or tumor tissue in a clinical laboratory improvement amendments (CLIA) certified laboratory (sites in the United Started \[US\]) or an accredited local laboratory (sites outside of the US)
- Have progressed on or after osimertinib (or another approved 3rd generation epidermal growth factor receptor \[EGFR\] tyrosine kinase inhibitor \[TKI\]) and platinum-based chemotherapy (irrespective of order). a) The 3rd generation EGFR TKI must have been administered as the first EGFR TKI for metastatic disease or as the second TKI after prior treatment with first- or second-generation EGFR TKI in participants with metastatic EGFR T790M mutation positive NSCLC. b) Participants who decline or are otherwise ineligible for chemotherapy may be enrolled after discussion with the medical monitor. c) Any adjuvant or neoadjuvant treatment, whether with a 3rd generation EGFR TKI or platinum based chemotherapy, would count towards the prior treatment requirement if the participant experienced disease
- Have at least 1 measurable lesion, according to response evaluation criteria in solid tumors (RECIST) version 1.1
- Have an eastern cooperative oncology group (ECOG) performance status of 0 to 1
- Any toxicities from prior anticancer therapy must have resolved to common terminology criteria for adverse events (CTCAE) Version 5.0 Grade 1 or baseline level (except for alopecia \[any grade\], Grade less than or equal to (\<=) 2 peripheral neuropathy, and Grade \<=2 hypothyroidism stable on hormone replacement)
You may not qualify if:
- Participant has received cytotoxic, investigational, or targeted therapies beyond one regimen of platinum-based chemotherapy and EGFR inhibitors
- Participant has received radiotherapy for palliative purposes less than 7 days prior to randomization
- Participant has symptomatic or progressive brain metastases
- Participant has leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation
- Participant has uncontrolled tumor-related pain
- Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (187)
City of Hope Duarte
Duarte, California, 91010, United States
City of Hope Orange County Lennar Foundation Cancer Center
Irvine, California, 92618, United States
City of Hope Long Beach Elm
Long Beach, California, 90813, United States
National Jewish Health
Denver, Colorado, 80206, United States
Baptist Lynn Cancer Institute
Boca Raton, Florida, 33486, United States
Orlando Health
Orlando, Florida, 32806, United States
University of Kansas
Kansas City, Kansas, 66160, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Astera Cancer Care
East Brunswick, New Jersey, 08816, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901, United States
NYU Langone Health Laura and Isaac Perlmutter Cancer Center
New York, New York, 10016, United States
Montefiore Medical Center
The Bronx, New York, 10461, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Providence Oncology and Hematology Care Clinic Westside
Portland, Oregon, 97225, United States
University of Pennsylvania Division of Hematology Oncology Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania, 19104, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Virginia Cancer Specialists
Fairfax, Virginia, 22031, United States
CEMIC (Centro de Educación Médica e Investigaciones Clínicas)
Buenos Aires, 1431, Argentina
Centro Oncológico Korben
Buenos Aires, C1426AGE, Argentina
IADT Instituto Argentino de Diagnostico y Tratamiento
CABA, C1122, Argentina
Cemaic Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica
Córdoba, 5000, Argentina
Sanatorio Allende
Córdoba, 5000, Argentina
Clínica Viedma
Viedma, R8500ACE, Argentina
Cancer Research SA
Adelaide, 5000, Australia
Chris O'Brien Lifehouse
Camperdown, 2050, Australia
Peter MacCallum Cancer Centre
Melbourne, 3000, Australia
St John of God Hospital Murdoch
Murdoch, 6150, Australia
Westmead Hospital
Westmead, 2145, Australia
Princess Alexandra Hospital
Woolloongabba, 4102, Australia
Fundacao Pio XII
Barretos, 14784-400, Brazil
Cetus Oncologia
Belo Horizonte, 30110-017, Brazil
Instituto Cionc de Ensino e Pesquisa S/S
Curitiba, 80810-050, Brazil
Ynova Pesquisa Clinica
Florianópolis, 88020-210, Brazil
Fundacao Sao Francisco Xavier HMC Unidade de Oncologia
Ipatinga, 35162 189, Brazil
UPCO Unidade de Pesquisa Clinica em Oncologia
Pelotas, 96020 080, Brazil
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS
Porto Alegre, 90610-000, Brazil
Impar Servicos Hospitalares S/A
Rio de Janeiro, 22061-080, Brazil
Oncoclinicas Rio de Janeiro S A
Rio de Janeiro, 22250 905, Brazil
Instituto D Or de Pesquisa e Ensino IDOR
Rio de Janeiro, 22281 100, Brazil
Nucleo de Oncologia da Bahia
Salvador, 40170 110, Brazil
CEPHO Centro de Estudos e Pesquisa de Hematologia e Oncologia
Santo André, 09060-650, Brazil
Impar Servicos Hospitalares SA Hospital Nove de Julho
São Paulo, 01409-002, Brazil
Núcleo de Pesquisa São Camilo
São Paulo, 04014-002, Brazil
Onco Star SP Oncologia Ltda
São Paulo, 04543-000, Brazil
Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
São Paulo, 05652 900, Brazil
The Ottawa Hospital Cancer Centre
Ottawa, Ontario, K1H 8L6, Canada
Princess Margaret Hospital
Toronto, Ontario, M5G 1Z5, Canada
Beijing Shijitan Hospital, Capital Medical University
Beijing, 100038, China
Beijing Friendship Hospital Capital Medical University
Beijing, 100050, China
Peking University Third Hospital
Beijing, 100191, China
Beijing Chest hospital, Capital medical university
Beijing, 101149, China
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, 200240, China
Jilin cancer hospital
Changchun, 130012, China
The First People's Hospital Of Changzhou
Changzhou, 213004, China
Sichuan Cancer Hospital
Chengdu, 610041, China
West China Hospital Sichuan University
Chengdu, 610047, China
Chongqing University Cancer Hospital
Chongqing, 400030, China
Southwest Hospital
Chongqing, 400038, China
First Affiliated Hospital of Gannan Medical University
Ganzhou, 341000, China
Sun Yat-Sen Memorial Hospital Sun Yat-sen University
Guangzhou, 510000, China
The First Affiliated Hospital Sun Yat sen University
Guangzhou, 510080, China
The Second Affiliated Hospital of Zhejiang University College of Medicine
Hangzhou, 310009, China
Sir Run Run Shaw Hospital Zhejiang University School of Medicine
Hangzhou, 310016, China
Zhejiang Cancer Hospital
Hangzhou, 310022, China
Harbin medical university cancer hospital
Harbin, 150081, China
Huizhou Municipal Central Hospital
Huizhou, 516001, China
Huizhou First Hospital
Huizhou, 516003, China
Liuzhou people's Hospital
Liuchow, 545026, China
Affiliated Hospital of North Sichuan Medical College
Nanchong, 637100, China
Fudan University Shanghai Cancer Center
Shanghai, 200032, China
Shengjing Hospital Of China Medical University
Shenyang, 110004, China
Shenzhen People s Hospital
Shenzhen, 518001, China
Shenzhen university General Hospital
Shenzhen, 518055, China
Tianjin Medical University Cancer Institute and Hospital
Tianjin, 300060, China
Union Hospital Tongji Medical College of Huazhong University of Science and Technology
Wuhan, 430022, China
The First Affiliated Hospital of Xian Jiaotong University
Xi'an, 710061, China
Xiangyang Central Hospital
Xiangyang, 441021, China
Yantai Yuhuangding Hospital
Yantai, 264000, China
Henan Cancer Hospital
Zhengzhou, 450008, China
CHU Grenoble
La Tronche, 38700, France
Institute Coeur Poumon
Lille, 59000, France
CHU de Limoges Hopital Dupuytren
Limoges, 87000, France
Hopital Nord
Marseille, 13915, France
Evangelische Lungenklinik Berlin
Berlin, 13125, Germany
Niels-Stensen-Kliniken Franziskus-Hospital Harderberg
Georgsmarienhütte, 49124, Germany
Universitaetsklinikum Giessen und Marburg GmbH
Giessen, 35392, Germany
Munster University Hospital
Münster, 48149, Germany
Oncologianova GmbH
Recklinghausen, 45659, Germany
Onkologische Schwerpunktpraxis
Weinsberg, 74189, Germany
Rambam Medical Center
Haifa, 3109601, Israel
Shaare Zedek Medical Center
Jerusalem, 91031, Israel
Meir Medical Center
Kfar Saba, 44281, Israel
Rabin Medical Center
Petah Tikva, 49100, Israel
Chaim Sheba Medical Center
Ramat Gan, 5262100, Israel
Oncologia Medica - Irccs - Istituto Tumori Giovanni Paolo II
Bari, 70124, Italy
A O U Sant Orsola Malpighi
Bologna, 40138, Italy
European Institute of Oncology
Milan, 20141, Italy
Aou San Luigi Gonzaga
Orbassano, 10043, Italy
Istituto Oncologico Veneto - IRCCS
Padova, 35128, Italy
Ospedale S. Maria Delle Croci
Ravenna, 48121, Italy
A.O. San Camillo Forlanini
Roma, 00152, Italy
Istituto Nazionale Tumori Regina Elena
Rome, 00144, Italy
Istituto Clinico Humanitas
Rozzano, 20089, Italy
National Cancer Center Hospital
Chūōku, 104 0045, Japan
National Hospital Organization Himeji Medical Center
Himeji, 670-8520, Japan
Kansai Medical University Hospital
Hirakata, 573 1191, Japan
Kanagawa Cancer Center
Kanagawa, 241-8515, Japan
Kurashiki Central Hospital
Kurashiki, 710-8602, Japan
Kurume University Hospital
Kurume, 830-0011, Japan
Matsusaka Municipal Hospital
Matsusaka, 515-8544, Japan
Niigata Cancer Center Hospital
Niigata, 951-8566, Japan
Okayama University Hospital
Okayama, 700 8558, Japan
Osaka International Cancer Institute
Osaka, 541 8567, Japan
Hokkaido University Hospital
Sapporo, 060-8648, Japan
Shizuoka Cancer Center
Shizuoka, 411 8777, Japan
The Cancer Institute Hospital of JFCR
Tokyo, 135 8550, Japan
Fujita Health University Hospital
Toyoake, 470-1192, Japan
National Hospital Organization Osaka Toneyama Medical Center
Toyonaka-shi, 560-8552, Japan
Wakayama Medical University Hospital
Wakayama, 641 8510, Japan
National Hospital Organization Iwakuni Clinical Center
Yamaguchi, 740-8510, Japan
National Hospital Organization Yamaguchi Ube Medical Center
Yamaguchi, 755-0241, Japan
Prince Court Medical Centre
Kuala Lumpur, 50450, Malaysia
Pantai Hospital Kuala Lumpur
Kuala Lumpur, 59100, Malaysia
University Malaya Medical Centre
Kuala Lumpur, 59100, Malaysia
Hospital Umum Sarawak
Kuching, 93586, Malaysia
Beacon Hospital Sdn Bhd
Petaling Jaya, 46050, Malaysia
Sunway Medical Centre
Petaling Jaya, 47500, Malaysia
Centrum Onkologii im Prof F Lukaszczyka w Bydgoszczy
Bydgoszcz, 85 796, Poland
Krakowski Szpital Specjalityczny im. Jana Pawla II
Krakow, 31-202, Poland
Mazowieckie Centrum Leczenia Chorob Pluc
Otwock, 05 400, Poland
Private Specialist Hospitals - MedPolonia
Poznan, 60-693, Poland
Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
Warsaw, 02-781, Poland
Hospital de Braga
Braga, 4710-243, Portugal
Hospital da Luz, SA
Lisbon, 1500-650, Portugal
Hosp. Cuf Descobertas
Lisbon, 1998-018, Portugal
Ulsm - Hosp. Pedro Hispano
Senhora da Hora, 4464-513, Portugal
National Cancer Center
Gyeonggi-do, 10408, South Korea
CHA Bundang Medical Center, CHA University
Gyeonggi-do, 13496, South Korea
GyeongSang National University Hospital
Gyeongsangnam-do, 52727, South Korea
Chonnam National University Hwasun Hospital
Jeollanam-do, 58128, South Korea
Seoul National University Bundang Hospital
Seongnam-si, 13620, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Severance Hospital Yonsei University Health System
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Hosp Univ A Coruna
A Coruña, 15006, Spain
Hosp. Gral. Univ. de Alicante
Alicante, 03010, Spain
Hosp Univ Vall D Hebron
Barcelona, 08035, Spain
Hosp Clinic de Barcelona
Barcelona, 08036, Spain
Hosp. Univ. Quiron Dexeus
Barcelona, 8028, Spain
Hosp Reina Sofia
Córdoba, 14004, Spain
Hosp. Univ. Insular de Gran Canaria
Las Palmas de Gran Canaria, 35016, Spain
Hosp. Univ. Lucus Augusti
Lugo, 27003, Spain
Hosp. Gral. Univ. Gregorio Maranon
Madrid, 28009, Spain
Hosp. Univ. La Paz
Madrid, 28046, Spain
Hosp. Univ. Pta. de Hierro Majadahonda
Majadahonda, 28222, Spain
Hosp Regional Univ de Malaga
Málaga, 29011, Spain
Hosp. Univ. Central de Asturias
Oviedo, 33011, Spain
Hosp. Univ. Son Espases
Palma de Mallorca, 07120, Spain
Hosp. Virgen Del Rocio
Seville, 41013, Spain
Hosp. Univ. I Politecni La Fe
Valencia, 46026, Spain
Changhua Christian Hospital
Changhua, 50006, Taiwan
Kaohsiung Medical University Chung Ho Memorial Hospital
Kaohsiung City, 80756, Taiwan
Chang Kung Memorial Hospital
Kaohsiung City, 833, Taiwan
Chung Shan Medical University Hospital
Taichung, 403, Taiwan
National Cheng Kung University Hospital
Tainan, 70403, Taiwan
National Taiwan University Hospital
Taipei, 10048, Taiwan
National Taiwan University Cancer Center
Taipei, 106, Taiwan
Linkou Chang Gung Memorial Hospital
Taoyuan District, 33382, Taiwan
Phramongkutklao Hospital and Medical College
Bangkok, 10400, Thailand
Siriraj Hospital
Bangkok, 10700, Thailand
Chiang Mai University
Chiang Mai, 50200, Thailand
Adana City Hospital
Adana, 01060, Turkey (Türkiye)
Adana Baskent Hospital
Adana, 01120, Turkey (Türkiye)
Memorial Ankara Hastanesi
Ankara, 06520, Turkey (Türkiye)
Gazi University Hospital
Ankara, 06560, Turkey (Türkiye)
Ankara Bilkent City Hospital
Ankara, 06800, Turkey (Türkiye)
Trakya University Medical Faculty
Edirne, 22030, Turkey (Türkiye)
Istanbul University Cerrahpasa Medical Faculty
Istanbul, 34098, Turkey (Türkiye)
Acıbadem Maslak Hospital
Istanbul, 34457, Turkey (Türkiye)
Dokuz Eylul University Medical Faculty
Izmir, 35330, Turkey (Türkiye)
IEU Medical Point Hospital
Izmir, 35575, Turkey (Türkiye)
Medical Park Samsun Hastanesi
Samsun, 55200, Turkey (Türkiye)
Birmingham Heartlands Hospital
Birmingham, B9 5SS, United Kingdom
Imperial College Healthcare
London, W2 1NY, United Kingdom
Newcastle Freeman Hospital
Newcastle upon Tyne, NE7 7DN, United Kingdom
Royal Marsden Hospital
Sutton, SM2 5PT, United Kingdom
Related Publications (1)
Leighl NB, Akamatsu H, Lim SM, Cheng Y, Minchom AR, Marmarelis ME, Sanborn RE, Chih-Hsin Yang J, Liu B, John T, Massuti B, Spira AI, Lee SH, Wang J, Li J, Liu C, Novello S, Kondo M, Tamiya M, Korbenfeld E, Moskovitz M, Han JY, Alexander M, Joshi R, Felip E, Voon PJ, Danchaivijitr P, Hsu PC, Silva Melo Cruz FJ, Wehler T, Greillier L, Teixeira E, Nguyen D, Sabari JK, Qin A, Kowalski D, Sendur MAN, Xie J, Ghosh D, Alhadab A, Haddish-Berhane N, Clemens PL, Lorenzini P, Verheijen RB, Gamil M, Bauml JM, Baig M, Passaro A; PALOMA-3 Investigators. Subcutaneous Versus Intravenous Amivantamab, Both in Combination With Lazertinib, in Refractory Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: Primary Results From the Phase III PALOMA-3 Study. J Clin Oncol. 2024 Oct 20;42(30):3593-3605. doi: 10.1200/JCO.24.01001. Epub 2024 Jun 10.
PMID: 38857463DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Janssen Research & Development, LLC
Study Officials
- STUDY DIRECTOR
Janssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
May 19, 2022
First Posted
May 24, 2022
Study Start
August 5, 2022
Primary Completion
January 3, 2024
Study Completion (Estimated)
June 30, 2027
Last Updated
April 13, 2026
Results First Posted
February 2, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& 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