A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (PALOMA-2)

August 27, 2026 updated by: Janssen Research & Development, LLC

A Phase 2, Open-Label, Parallel Cohort Study of Subcutaneous Amivantamab in Multiple Regimens in Patients With Advanced or Metastatic Solid Tumors Including EGFR-mutated Non-Small Cell Lung Cancer

The purpose of this study is to assess the anti-tumor activity and safety of amivantamab which will be administered as a co-formulation with recombinant human hyaluronidase PH20 (rHuPH20) (subcutaneous co-formulation [SC-CF]) in combination treatment (all cohorts except Cohort 4) and to characterize the safety of amivantamab SC-CF (Cohort 4).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 80 percent (%) to 85% of lung cancers with epidermal growth factor receptor (EGFR) mutations, the Exon 19 deletion (Exon19del) and Exon 21 leucine 858 to arginine substitution (Exon 21 L858R) point mutations. Amivantamab is a low-fucose, fully human immunoglobulin (IgG)1-based bispecific antibody directed against EGFR and mesenchymal-epithelial transition (MET) tyrosine kinase receptors. The rationale for this study is to collect efficacy, safety, and PK data to support the use of amivantamab SC-CF in regimens and populations currently under study and approved with the IV formulation of amivantamab. The study will include a screening phase (28 days), a treatment phase (21 days [Cohorts 2 and 3] or 28 days [Cohort 1, 4, 5 and 6]), and a follow up phase (after last study treatment until disease progression or death, whichever comes first). Safety assessments will include physical examinations, vital signs, electrocardiograms (ECGs), echocardiograms, ophthalmologic assessments (All cohorts except cohort 4 and in Cohort 4 [where applicable]), laboratory tests, adverse event (AE) frequency and severity (by Common Terminology Criteria for Adverse Events [CTCAE] v5.0) monitoring, and concomitant medication use (all cohorts). The total duration of the study is up to 1 year 6 months.

Study Type

Interventional

Enrollment (Estimated)

520

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Brazil
      • Barretos, Brazil, 14784-400
        • Recruiting
        • Fundacao Pio XII
      • Belo Horizonte, Brazil, 30130 090
        • Recruiting
        • PERSONAL Oncologia de Precisao e Personalizada
      • Londrina, Brazil, 86015 520
        • Recruiting
        • Hospital do Câncer de Londrina
      • Porto Alegre, Brazil, 90035-001
        • Recruiting
        • Hospital Moinhos de Vento
      • Rio de Janeiro, Brazil, 22281 100
        • Recruiting
        • IDOR - Regional Rio de Janeiro
      • Salvador, Brazil, 41253-190
        • Recruiting
        • IDOR - Regional Bahia
      • São Paulo, Brazil, 01509 900
        • Recruiting
        • Fundacao Antonio Prudente A C Camargo Cancer Center
      • São Paulo, Brazil, 01327 001
        • Recruiting
        • Hospital Alemao Oswaldo Cruz
      • São Paulo, Brazil, 01409-001
        • Completed
        • Impar Servicos Hospitalares SA Hospital Nove de Julho
  • China
      • Baoding, China, 071051
        • Completed
        • Affiliated Hospital of Hebei University
      • Changchun, China, 130000
        • Recruiting
        • Jilin Cancer Hospital
      • Chengdu, China, 610041
        • Recruiting
        • Sichuan Cancer Hospital
      • Chengdu, China, 610047
        • Recruiting
        • West China Hospital Sichuan University
      • Chongqing, China, 400038
        • Recruiting
        • The First Affiliated Hospital of PLA Army Medical University
      • Guangzhou, China, 510060
        • Recruiting
        • The First Affiliated Hospital Sun Yat sen University
      • Hangzhou, China, 310003
        • Recruiting
        • The First Affiliated Hospital Zhejiang University College of Medicine
      • Hangzhou, China, 310016
        • Recruiting
        • Sir Run Run Shaw Hospital Zhejiang University School of Medicine
      • Harbin, China, 150000
        • Recruiting
        • Harbin Medical University Cancer Hospital
      • Huizhou, China, 516001
        • Recruiting
        • Huizhou Municipal Central Hospital
      • Liuzhou, China, 545006
        • Completed
        • Liuzhou People's Hospital
      • Shanghai, China, 200032
        • Recruiting
        • Fudan University Shanghai Cancer Center
      • Tianjin, China, 300052
        • Recruiting
        • Tianjin Medical University General Hospital
      • Wenzhou, China, 325000
        • Recruiting
        • The First Affiliated Hospital of Wenzhou Medical University
      • Wuhan, China, 430022
        • Recruiting
        • Union Hospital Tongji Medical College of Huazhong University of Science and Technology
      • Wuxi, China, 214122
        • Completed
        • Hospital of Jiangnan University
      • Xi'an, China, 710061
        • Recruiting
        • The First Affiliated Hospital of Xian Jiaotong University
      • Yantai, China, 264000
        • Completed
        • Yantai Yuhuangding Hospital
  • France
      • Caen, France, 14076
        • Recruiting
        • Centre Francois Baclesse
      • Dijon, France, 21079
        • Completed
        • Centre Georges-François Leclerc
      • Nîmes, France, 30029
        • Recruiting
        • Institut de cancerologie du Gard
      • Paris, France, 75248
        • Recruiting
        • Institut Curie
      • Saint-Herblain, France, 44805
        • Recruiting
        • Institut de Cancérologie de l'Ouest
      • Villejuif, France, 94800
        • Recruiting
        • Gustave Roussy
  • Germany
      • Berlin, Germany, 13125
        • Completed
        • Evangelische Lungenklinik Berlin
      • Cologne, Germany, 50937
        • Recruiting
        • Universitaetsklinikum Koeln
      • Grosshandorf, Germany, 22927
        • Recruiting
        • LungenClinic Grosshansdorf GmbH
      • Immenhausen, Germany, 34376
        • Recruiting
        • Lungenfachklinik Immenhausen
      • Würzburg, Germany, 97074
        • Recruiting
        • Klinikum Würzburg Mitte gGmbH Standort Missioklinik
  • Israel
      • Haifa, Israel, 3109601
        • Recruiting
        • Rambam Medical Center
      • Jerusalem, Israel, 9103102
        • Recruiting
        • Shaare Zedek Medical Center
      • Kfar Saba, Israel, 44281
        • Completed
        • Meir Medical Center
      • Petah Tikva, Israel, 4941492
        • Recruiting
        • Rabin Medical Center
      • Ramat Gan, Israel, 52621
        • Recruiting
        • Sheba Medical Center
  • Italy
      • Genova, Italy, 16132
        • Recruiting
        • Policlinico Hospital San Martino- IRCCS for Oncology
      • Milan, Italy, 20132
        • Recruiting
        • Ospedale San Raffaele
      • Milan, Italy, 20162
        • Recruiting
        • ASST Grande Ospedale Metropolitano Niguarda
      • Monza, Italy, 20090
        • Recruiting
        • Azienda Ospedaliera San Gerardo
      • Naples, Italy, 80131
        • Recruiting
        • Azienda Ospedaliera Specialistica dei Colli
  • Japan
      • Himeji, Japan, 670-8520
        • Active, not recruiting
        • National Hospital Organization Himeji Medical Center
      • Matsusaka, Japan, 515 8544
        • Active, not recruiting
        • Saiseikai Matsusaka Municipal Hospital
      • Niigata, Japan, 951-8566
        • Active, not recruiting
        • Niigata Cancer Center Hospital
      • Shizuoka, Japan, 411 8777
        • Active, not recruiting
        • Shizuoka Cancer Center
      • Tokyo, Japan, 135 8550
        • Active, not recruiting
        • The Cancer Institute Hospital of JFCR
      • Wakayama, Japan, 641 8510
        • Active, not recruiting
        • Wakayama Medical University Hospital
  • Malaysia
      • Kuala Lumpur, Malaysia, 59100
        • Recruiting
        • University Malaya Medical Centre
      • Kuantan, Malaysia, 25100
        • Recruiting
        • Hospital Tengku Ampuan Afzan
      • Kuching, Malaysia, 93586
        • Recruiting
        • Hospital Umum Sarawak
      • Petaling Jaya, Malaysia, 46050
        • Recruiting
        • Beacon Hospital Sdn Bhd
  • South Korea
      • Goyang-si, South Korea, 10408
        • Recruiting
        • National Cancer Center
      • Seongnam-si, South Korea, 13620
        • Recruiting
        • Seoul National University Bundang Hospital
      • Seoul, South Korea, 03080
        • Recruiting
        • Seoul National University Hospital
      • Seoul, South Korea, 03722
        • Recruiting
        • Severance Hospital Yonsei University Health System
      • Seoul, South Korea, 05505
        • Completed
        • Asan Medical Center
  • Spain
      • A Coruña, Spain, 15006
        • Recruiting
        • Hosp Univ A Coruna
      • Alicante, Spain, 03010
        • Recruiting
        • General University Hospital of Alicantet
      • Barcelona, Spain, 08025
        • Recruiting
        • Hosp. de La Santa Creu I Sant Pau
      • Barcelona, Spain, 08003
        • Recruiting
        • Hosp. Del Mar
      • Barcelona, Spain, 8908
        • Recruiting
        • Inst. Cat. Doncologia-H Duran I Reynals
      • Barcelona, Spain, 08035
        • Recruiting
        • Hosp Univ Vall D Hebron
      • Madrid, Spain, 28034
        • Recruiting
        • Hosp. Univ. Ramon Y Cajal
      • Madrid, Spain, 28041
        • Recruiting
        • Hosp. Univ. 12 de Octubre
      • Madrid, Spain, 28046
        • Recruiting
        • Hosp. Univ. La Paz
      • Madrid, Spain, 28007
        • Recruiting
        • Hosp. Gral. Univ. Gregorio Maranon
      • Málaga, Spain, 29010
        • Recruiting
        • Hosp Regional Univ de Malaga
      • Seville, Spain, 41009
        • Recruiting
        • Hosp. Virgen Macarena
      • Valencia, Spain, 46010
        • Recruiting
        • Hosp. Clinico Univ. de Valencia
      • Valencia, Spain, 46014
        • Recruiting
        • Hosp. Gral. Univ. Valencia
  • United Kingdom
      • Cheltenham, United Kingdom, GL53 7AN
        • Completed
        • Cheltenham General Hospital
      • Devon, United Kingdom, TQ2 7AA
        • Recruiting
        • Torbay Hospital-Devon
      • Edinburgh, United Kingdom, EH4 2XU
        • Recruiting
        • Edinburgh Cancer Centre Western General
      • Leicester, United Kingdom, LE1 5WW
        • Recruiting
        • Leicester Royal Infirmary
      • London, United Kingdom, NW1 2PG
        • Recruiting
        • University College London Hospitals
      • Nottingham, United Kingdom, NG5 1PB
        • Recruiting
        • Nottingham City Hospital
      • Portsmouth, United Kingdom, PO6 3LY
        • Recruiting
        • Queen Alexandra Hospital
  • United States
    • California
      • La Jolla, California, United States, 92093
        • Recruiting
        • University of California at San Diego
      • Orange, California, United States, 92868
        • Recruiting
        • University of California Irvine
      • Stanford, California, United States, 94305
        • Recruiting
        • Stanford Cancer Institute
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20016
        • Recruiting
        • Johns Hopkins Office of Capital Region Research - Sibley Memorial Hospital
    • Florida
      • Boca Raton, Florida, United States, 33486
        • Completed
        • Baptist Lynn Cancer Institute
      • Miami Beach, Florida, United States, 33140
        • Recruiting
        • Mount Sinai Medical Center
      • Orlando, Florida, United States, 32804
        • Recruiting
        • AdventHealth
      • Tampa, Florida, United States, 33612
        • Completed
        • H. Lee Moffitt Cancer & Research Institute
    • Kansas
      • Westwood, Kansas, United States, 66205
        • Recruiting
        • University of Kansas Cancer Center
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Recruiting
        • Sidney Kimmel Cancer Center - Bayview Campus
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Recruiting
        • Boston Medical Center
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • Hackensack University Medical Center
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Rutgers Cancer Institute of New Jersey
    • New York
      • East Syracuse, New York, United States, 13057
        • Completed
        • Hematology-Oncology Associates of CNY
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Completed
        • Novant Health 1
      • Winston-Salem, North Carolina, United States, 27106
        • Completed
        • Novant Health
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Completed
        • Cleveland Clinic
      • Cleveland, Ohio, United States, 44111
        • Completed
        • Cleveland Clinic 1
      • Mayfield Heights, Ohio, United States, 44124
        • Completed
        • Cleveland Clinic 2
      • Warrensville Heights, Ohio, United States, 44122
        • Completed
        • Cleveland Clinic 3
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Completed
        • The Huntsman Cancer Institute
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Virginia Cancer Specialists
    • Washington
      • Everett, Washington, United States, 98201
        • Completed
        • Providence Regional Cancer Partnership
      • Seattle, Washington, United States, 98104
        • Recruiting
        • Swedish Cancer Institute
      • Seattle, Washington, United States, 98101
        • Completed
        • Virginia Mason Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participant must have histologically or cytologically confirmed, locally advanced or metastatic, non-small cell lung cancer (NSCLC) that is not amenable to curative therapy including surgical resection or chemoradiation. Additional Cohort specific disease requirements include: Cohorts 1, 3, 3b, 5, 6 and 7: epidermal growth factor receptor (EGFR) exon 19 deletion (Exon19del) or Exon 21 L858R mutation; Cohort 2: EGFR Exon 20ins mutation. Cohorts 1,5,and6: Participant should not have received any prior systemic therapy for locally advanced or metastatic NSCLC. Cohort 2: Participant should not have received any prior systemic therapy for locally advanced or metastatic NSCLC. Cohorts 3and3b: 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. Cohort 4: Participants need to currently be on an amivantamab IV Q2W regimen (1,050 mg or 1,400 mg depending on weight) for at least 8 weeks, as part of standard of care, an expanded access program, or as a rollover from a long-term extension, without any amivantamab dose reduction. Cohort 7: Participants must have progressed on or after the combination of amivantamab and lazertinib as the most recent line of treatment. The combination of amivantamab and lazertinib must have been administered as the first-line treatment for locally advanced or metastatic disease. Cohort 2, 3, 3b, and 7 only: Squamous NSCLC are excluded. EGFR mutation must have been identified as determined by 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 states [US]) or an accredited local laboratory (sites outside of the US). A copy of the initial test report documenting the EGFR mutation must be included in the participant records and a deidentified copy must also be submitted to the sponsor
  • All cohorts except Cohort 4: Participants must have at least 1 measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. If the only target lesion has been previously irradiated, it must show signs of disease progression since radiation was completed If only 1 non-irradiated measurable lesion exists, which undergoes a biopsy and is acceptable as a target lesion, the baseline tumor assessment scans should be performed at least 14 days after the biopsy
  • May have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
  • Have adequate organ (renal, hepatic, hematological, coagulation and cardiac) functions
  • Participant must have eastern cooperative oncology group (ECOG) status of 0 or 1
  • Cohort 6: Must be eligible for, and agree to comply with, the use of prophylactic anticoagulation with a direct oral anticoagulant or a low molecular weight heparin during the first 4 months of study treatment
  • A participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 6 months after receiving the last dose of study treatment. Participants with child bearing potential should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility

Exclusion Criteria:

  • Participant has a medical history of interstitial lung disease (ILD), including drug induced ILD or radiation pneumonitis
  • Participant has a history of hypersensitivity to any excipients of the investigational products to be used in their enrollment cohort
  • Participant has received a live or live attenuated vaccine within 3 months before Cycle 1 Day 1. The seasonal influenza vaccine and non-live vaccines against Coronavirus disease 19 (COVID-19) are not exclusionary
  • For all cohorts (with regimens potentially including lazertinib): Participant is currently receiving medications or herbal supplements known to be potent Cytochrome (CYP3A4/5) inducers and is unable to stop use for an appropriate washout period prior to Cycle 1 Day 1
  • Other clinically active liver disease of infectious origin
  • Participant has a history of clinically significant cardiovascular disease including, but not limited to: a) All cohorts: diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior to the first dose of study treatment(s), or any of the following within 6 months prior to the first dose of study treatment(s): myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary/peripheral artery bypass graft, or any acute coronary syndrome. Clinically non-significant thrombosis, such as non-obstructive catheter-associated clots, are not exclusionary; b) All cohorts (with regimens potentially including lazertinib): Participant has a significant genetic predisposition to venous thromboembolic events (VTE; such as Factor V Leiden); c) All cohorts (with regimens potentially including lazertinib): Participant has a prior history of VTE and is not on appropriate therapeutic anticoagulation as per NCCN or local guidelines; d) prolonged corrected QT interval by Fridericia (QTcF) interval greater than (>) 480 milliseconds (msec) or clinically significant cardiac arrhythmia or electrophysiologic disease (example, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate); e) uncontrolled (persistent) hypertension: systolic blood pressure >160 millimeter(s) of mercury (mmHg); diastolic blood pressure >100 mmHg; f) Congestive heart failure defined as NYHA class III-IV or hospitalization for congestive heart failure (CHF) (any New York Heart Association [NYHA] class) within 6 months of treatment initiation at Cycle 1/day 1 (C1D1); g) pericarditis/clinically significant pericardial effusion; h) myocarditis; i) baseline left ventricular ejection fraction (LVEF) below the institution's lower limit of normal at screening, as assessed by echocardiogram or multigated acquisition (MUGA) scan
  • Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants who have received definitive radiation or surgical treatment for symptomatic or unstable brain metastases and have been clinically stable and asymptomatic for at least 2 weeks before Screening are eligible, provided they have been either off corticosteroid treatment or are receiving low-dose corticosteroid treatment (less than or equal to [<=] 10 milligrams per day [mg/day] prednisone or equivalent) for at least 2 weeks prior to treatment allocation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1(Exon19del/Exon21 L858R NSCLC, 1L, Previously Untreated): Amivantamab (Q2W) + Lazertinib
Participants with treatment-naive locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) exon 19 deletion (exon19del) or exon 21 leucine 858 to arginine substitution (exon 21 L858R) mutation, will receive amivantamab SC-CF injection, 1600 milligrams (mg) or 2240 mg if body weight is greater than or equal to (>=) 80 kilograms (kg), on Cycle 1 Days 1, 8, 15, and 22 and on Days 1 and 15 of each subsequent 28-day cycle, starting with Cycle 2, along with lazertinib 240 mg orally once daily. Eligible participants will be given an option to enter long-term extension (LTE) phase and may continue to receive access to study treatment(s) within the study by transferring to the Drug Access (DA)-LTE Phase.
Drug: Amivantamab
Amivantamab will be administered subcutaneously by manual injection.
Other Names:
  • JNJ-61186372
Drug: Lazertinib
Lazertinib will be administered as an oral tablet.
Other Names:
  • JNJ-73841937; YH25448
Experimental: Cohort 2(Exon20 NSCLC,1L, Previously Untreated): Amivantamab (Q3W) + Chemotherapy
Participants with treatment-naive locally advanced or metastatic NSCLC harboring an EGFR exon20ins mutation will receive Amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is >=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is >=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle, starting with Cycle 2 along with pemetrexed 500 milligrams per meter square (mg/m^2) as intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle and IV infusion carboplatin area under the concentration-time curve 5 milligrams per milliliters (mg/mL) per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles. Eligible participants will be given an option to enter LTE phase and may continue to receive access to study treatment(s) within the study by transferring to the DA-LTE Phase.
Drug: Amivantamab
Amivantamab will be administered subcutaneously by manual injection.
Other Names:
  • JNJ-61186372
Drug: Carboplatin
Carboplatin will be administrated by IV infusion.
Drug: Pemetrexed
Pemetrexed will be administered by IV infusion.
Experimental: Cohort 3(Exon19del/Exon21 L858R NSCLC,2L,Post Osimertinib):Amivantamab(Q3W)+Lazertinib+Chemotherapy
Participants with locally advanced or metastatic NSCLC harboring an EGFR exon19del or exon 21 L858R mutation who have experienced disease progression on or after treatment with a third-generation EGFR TKI (osimertinib), will receive amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is >=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is >=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle starting with Cycle 2; in combination with IV infusion carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles; and pemetrexed 500 mg/m^2 as an IV infusion (with vitamin supplementation) on Day 1 of each 21-day until disease progression. Lazertinib 240 mg orally once daily starting Cycle 5 Day 1 when carboplatin is complete or sooner if carboplatin discontinued earlier than Cycle 4. Eligible participants will be given an option to enter LTE phase and DA-LTE Phase.
Drug: Amivantamab
Amivantamab will be administered subcutaneously by manual injection.
Other Names:
  • JNJ-61186372
Drug: Lazertinib
Lazertinib will be administered as an oral tablet.
Other Names:
  • JNJ-73841937; YH25448
Drug: Carboplatin
Carboplatin will be administrated by IV infusion.
Drug: Pemetrexed
Pemetrexed will be administered by IV infusion.
Experimental: Cohort 3b(Exon19del/Exon21 L858R NSCLC, 2L, Post Osimertinib): Amivantamab (Q3W)+Chemotherapy
Participants with locally advanced or metastatic NSCLC harboring an EGFR exon19del or exon 21 L858R mutation who have experienced disease progression on or after treatment with a third-generation EGFR TKI (osimertinib), will receive amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is >=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is >=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle starting with Cycle 2; in combination with IV infusion carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles; and pemetrexed 500 mg/m^2 as an IV infusion (with vitamin supplementation) on Day 1 of each 21-day until disease progression. Eligible participants will be given an option to enter LTE phase and may continue to receive access to study treatment(s) within the study by transferring to the DA-LTE Phase.
Drug: Amivantamab
Amivantamab will be administered subcutaneously by manual injection.
Other Names:
  • JNJ-61186372
Drug: Carboplatin
Carboplatin will be administrated by IV infusion.
Drug: Pemetrexed
Pemetrexed will be administered by IV infusion.
Experimental: Cohort 4(Previously Treated with Amivantamab IV): Switch from Amivantamab IV to SC-CF (Q2W)
Participants who were previously on amivantamab IV once every 2 weeks (Q2W) regimen as part of standard of care, for at least 8 weeks, either as monotherapy or combination with lazertinib, will receive amivantamab SC-CF injection 1600 mg and 2240 mg if body weight is greater than or equal to 80 kg. Participants who continue to benefit from study treatments, as determined by their investigator, may shift to the drug access (DA)-LTE phase.
Drug: Amivantamab
Amivantamab will be administered subcutaneously by manual injection.
Other Names:
  • JNJ-61186372
Drug: Lazertinib
Lazertinib will be administered as an oral tablet.
Other Names:
  • JNJ-73841937; YH25448
Experimental: Cohort 5(Exon19del/Exon21 L858R NSCLC, 1L, Previously Untreated): Amivantamab (Q4W) + Lazertinib
Participants with treatment-naïve locally advanced or metastatic NSCLC harboring an EGFR Exon19del or Exon 21 L858R mutation will receive amivantamab SC-CF induction with 1,600 mg (or 2,240 mg if BW >=80 kg) on Cycle 1 Days 1, 8, 15, and 22, starting with Cycle 2 on Day 1 of each next 28-day cycle, amivantamab SC-CF (160 mg/mL co-formulated with rHuPH20) by manual injection at 3,520 mg (or 4,640 mg if BW >=80 kg); along with lazertinib 240 mg by mouth once daily from Cycle 1 Day 1. Eligible participants will be given an option to enter LTE phase and may continue to receive access to study treatment(s) within the study by transferring to the DA-LTE Phase.
Drug: Amivantamab
Amivantamab will be administered subcutaneously by manual injection.
Other Names:
  • JNJ-61186372
Drug: Lazertinib
Lazertinib will be administered as an oral tablet.
Other Names:
  • JNJ-73841937; YH25448
Experimental: Cohort6(Exon19del/Exon21L858R,NSCLC1L,PreviouslyUntreated):Amivantamab(Q2W)+Lazertinib+Anticoagulant
Participants with treatment-naive locally advanced or metastatic NSCLC harboring an EGFR Exon19del or Exon 21 L858R mutation treated will receive will receive amivantamab SC-CF injection, 1600 milligrams (mg) and 2240 mg if body weight is greater than or equal to (>=) 80 kilograms (kg), on Cycle 1 Days 1, 8, 15, and 22 and on Days 1 and 15 of each subsequent 28-day cycle, starting with Cycle 2, along with lazertinib 240 mg orally once daily from Cycle 1 Day 1. Participants will additionally take prophylactic anticoagulation with a direct oral anticoagulant (DOAC) or a low molecular weight heparin (LMWH) for the first four months of study treatment (from Day 1 through Day 120) with the combination of amivantamab and lazertinib. Eligible participants will be given an option to enter LTE phase and may continue to receive access to study treatment(s) within the study by transferring to the DA-LTE Phase.
Drug: Amivantamab
Amivantamab will be administered subcutaneously by manual injection.
Other Names:
  • JNJ-61186372
Drug: Lazertinib
Lazertinib will be administered as an oral tablet.
Other Names:
  • JNJ-73841937; YH25448
Drug: Direct Oral Anticoagulant (DOAC)
DOAC will be administered orally.
Drug: Low Molecular Weight Heparin (LMWH)
LMWH will be administered subcutaneously.
Experimental: Cohort 7(Exon19del/Exon21 L858R NSCLC,2L,Post Amivantamab+Lazertinib):Amivantamab(Q3W)+Chemotherapy
Participants with locally advanced or metastatic NSCLC harboring an EGFR exon19del or exon 21 L858R mutation who have experienced disease progression on or after the combination of amivantamab and lazertinib will receive amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is >=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is >=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle starting with Cycle 2; in combination with IV infusion carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles; and pemetrexed 500 mg/m^2 as an IV infusion (with vitamin supplementation) on Day 1 of each 21-day until disease progression. Eligible participants will be given an option to enter LTE phase and may continue to receive access to study treatment(s) within the study by transferring to the DA-LTE Phase.
Drug: Amivantamab
Amivantamab will be administered subcutaneously by manual injection.
Other Names:
  • JNJ-61186372
Drug: Carboplatin
Carboplatin will be administrated by IV infusion.
Drug: Pemetrexed
Pemetrexed will be administered by IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All Cohorts Except Cohort 4: Objective Response Rate (ORR) Based on Investigator Assessment (INV)
Time Frame: Up to 1 year 6 months
ORR based on INV will be reported. ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR), based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as determined by investigator.
Up to 1 year 6 months
Cohort 4: Number of Participants with Adverse Events (AEs)
Time Frame: Up to approximately 4 years and 9 months
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study.
Up to approximately 4 years and 9 months
Cohort 4: Number of Participants with AEs by Severity
Time Frame: Up to approximately 4 years and 9 months
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Up to approximately 4 years and 9 months
Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values
Time Frame: Up to approximately 4 years and 9 months
Number of participants with abnormalities in clinical laboratory values (which includes serum chemistry, hematology, coagulation, urinalysis, and serology) will be reported.
Up to approximately 4 years and 9 months
Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values by Severity
Time Frame: Up to approximately 4 years and 9 months
Number of participants with laboratory values abnormalities which includes serum chemistry, hematology, coagulation, urinalysis, and serology) by severity will be reported. Severity of laboratory values abnormalities will be graded according to the NCI-CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Up to approximately 4 years and 9 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cohort 4: Patient-reported Status as Assessed by Patient Global Impression of Change (PGIC) Scale Score
Time Frame: Up to 1 year 6 months
Patient-reported status as assessed by PGIC scale score will be reported. The PGIC is an assessment of the participant's overall sense of whether there has been a change since starting treatment. The PGIC is a 7-point response scale. Participants will be asked to rate their current fatigue as compared to when they started the study, using the following 7-point scale: 1 = Much better, 2 = Moderately better, 3 = A little better, 4 = No change, 5 = A little worse, 6 = Moderately worse, and 7 = Much worse.
Up to 1 year 6 months
Cohort 4: Patient-reported Status as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score
Time Frame: Up to 1 year 6 months
Patient-reported status as assessed by PGIS scale score will be reported. The PGIS is an assessment of lung cancer severity at a given point in time. The PGIS is a 5-point response scale. Participants will be asked to rate their fatigue over the past 7 days using the following 5-point scale: 1 = None, 2 = Mild, 3 = Moderate, 4 = Severe, and 5 = Very severe.
Up to 1 year 6 months
All Cohorts Except Cohort 4: Number of Participants with AEs
Time Frame: Up to 1 year 6 months
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study.
Up to 1 year 6 months
All Cohorts Except Cohort 4: Number of Participants with AEs by Severity
Time Frame: Up to 1 year 6 months
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Up to 1 year 6 months
All Cohorts Except Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values
Time Frame: Up to 1 year 6 months
Number of participants with abnormalities in clinical laboratory values (which includes serum chemistry, hematology, coagulation, urinalysis, and serology) will be reported.
Up to 1 year 6 months
All Cohorts Except Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values by Severity
Time Frame: Up to 1 year 6 months
Number of participants with abnormalities in clinical laboratory values which includes serum chemistry, hematology, coagulation, urinalysis, and serology) by severity will be reported. Severity of laboratory values abnormalities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Up to 1 year 6 months
All Cohorts Except Cohort 4: ORR Based on Independent Central Review (ICR)
Time Frame: Up to 1 year 6 months
ORR based on ICR will be reported. The ORR is defined as the percentage of participants who achieve a CR or PR, based on RECIST version 1.1, as confirmed by ICR.
Up to 1 year 6 months
All Cohorts Except Cohort 4: Duration of Response (DoR) Based on Investigator Assessment (INV)
Time Frame: Up to 1 year 6 months
DoR based on INV is defined as the time from the date of first documented response (PR or CR) until the date of documented progression or death, whichever comes first, for participants who have PR or CR.
Up to 1 year 6 months
All Cohorts Except Cohort 4: Time to Response (TTR) Based on INV
Time Frame: Up to 1 year 6 months
TTR (that is, time to first response) based on INV is defined as the time from the first dose of study treatment to the date of first documentation of a response (PR or CR) prior to any disease progression and subsequent anticancer therapy, based on RECIST version 1.1., for participants who have PR or CR as their best response.
Up to 1 year 6 months
All Cohorts Except Cohort 4: Clinical Benefit Rate (CBR)
Time Frame: Up to 1 year 6 months
CBR is defined as the percentage of participants achieving CR or PR, or durable standard deviation (SD) of a duration of at least 11 weeks as defined by RECIST version 1.1.
Up to 1 year 6 months
All Cohorts Except Cohort 4: Number of Participants with Venous Thromboembolic Events (VTE)
Time Frame: Up to 1 year 6 months
Number of participants with adverse events of VTE (pulmonary embolism and deep vein thrombosis) will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study.
Up to 1 year 6 months
All Cohorts Except Cohort 4: Number of Participants with Venous Thromboembolic Events (VTE) by Severity
Time Frame: Up to 1 year 6 months
Number of participants with adverse events of VTE (pulmonary embolism and deep vein thrombosis) by severity will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death).
Up to 1 year 6 months
All Cohorts Except Cohort 4: Serum Concentration Immediately Prior to the Next Dose Administration (Ctrough) of Amivantamab
Time Frame: Cycle 2 Day 1 of 28-day cycle
Ctrough is defined as the serum concentration of amivantamab immediately prior to the next drug administration.
Cycle 2 Day 1 of 28-day cycle
Cohort 4: Cancer Therapy Satisfaction as Assessed by Modified Therapy Administration Satisfaction Questionnaire - Intravenous (TASQ-IV)
Time Frame: Up to 1 year 6 months
Patient-reported outcome (PRO): Cancer therapy satisfaction will be assessed using the modified TASQ-IV. The modified TASQ is a 12-item questionnaire measuring the impact of each mode of treatment administration on five domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each of the domain/scale scores is scored on a 1-100 scale, where 0 is worst and 100 is best.
Up to 1 year 6 months
Cohort 4: Cancer Therapy Satisfaction as Assessed by Modified Therapy Administration Satisfaction Questionnaire - Subcutaneous (TASQ-SC)
Time Frame: Up to 1 year 6 months
PRO: Cancer therapy satisfaction will be assessed using the modified TASQ-SC. The modified TASQ is a 12-item questionnaire measuring the impact of each mode of treatment administration on five domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each of the domain/scale scores is scored on a 1-100 scale, where 0 is worst and 100 is best.
Up to 1 year 6 months
All Cohorts Except Cohort 4: Progression-free Survival (PFS)
Time Frame: Up to 3 years
The PFS is defined as the time from the first dose of study treatment until the date of objective disease progression or death, whichever comes first, based on RECIST version 1.1.
Up to 3 years
All Cohorts Except Cohort 4: Overall Survival (OS)
Time Frame: Up to approximately 4 years
The OS is defined as the time from the first dose of study treatment until the date of death due to any cause.
Up to approximately 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Janssen Research & Development, LLC

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 11, 2022

Primary Completion (Estimated)

August 17, 2027

Study Completion (Estimated)

August 18, 2028

Study Registration Dates

First Submitted

August 10, 2022

First Submitted That Met QC Criteria

August 10, 2022

First Posted (Actual)

August 12, 2022

Study Record Updates

Last Update Posted (Actual)

August 28, 2026

Last Update Submitted That Met QC Criteria

August 27, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR109264
  • 2023 (U.S. NIH Grant/Contract: GRAMMY Museum Foundation)
  • 2022-000526-21 (EudraCT Number)
  • 61186372NSC2002 (Other Identifier: Janssen Research & Development, LLC)
  • 2023-505065-91-00 (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 www.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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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