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A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer
NCT05498428 · Janssen Research & Development, LLC
In plain English
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Official title
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
About this study
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).
Eligibility criteria
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 design
Enrollment target: 520 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2022-11-11
Estimated completion: 2028-08-18
Last updated: 2026-06-05
Interventions
Drug: AmivantamabDrug: LazertinibDrug: CarboplatinDrug: PemetrexedDrug: Direct Oral Anticoagulant (DOAC)Drug: Low Molecular Weight Heparin (LMWH)
Primary outcomes
- • All Cohorts Except Cohort 4: Objective Response Rate (ORR) Based on Investigator Assessment (INV) (Up to 1 year 6 months)
- • Cohort 4: Number of Participants with Adverse Events (AEs) (Up to approximately 4 years and 9 months)
- • Cohort 4: Number of Participants with AEs by Severity (Up to approximately 4 years and 9 months)
Sponsor
Janssen Research & Development, LLC · industry
Contacts & investigators
ContactStudy Contact · contact · Participate-In-This-Study1@its.jnj.com · 844-434-4210
InvestigatorJanssen Research & Development, LLC Clinical Trial · study_director, Janssen Research & Development, LLC
All locations (110)
University of California at San DiegoRecruiting
La Jolla, California, United States
University of California IrvineRecruiting
Orange, California, United States
Stanford Cancer InstituteRecruiting
Stanford, California, United States
Johns Hopkins Office of Capital Region Research - Sibley Memorial HospitalRecruiting
Washington D.C., District of Columbia, United States
Baptist Lynn Cancer InstituteCompleted
Boca Raton, Florida, United States
Mount Sinai Medical CenterRecruiting
Miami Beach, Florida, United States
AdventHealthRecruiting
Orlando, Florida, United States
H. Lee Moffitt Cancer & Research InstituteCompleted
Tampa, Florida, United States
University of Kansas Cancer CenterRecruiting
Westwood, Kansas, United States
Sidney Kimmel Cancer Center - Bayview CampusRecruiting
Baltimore, Maryland, United States
Boston Medical CenterRecruiting
Boston, Massachusetts, United States
Washington University School Of MedicineRecruiting
St Louis, Missouri, United States
Hackensack University Medical CenterRecruiting
Hackensack, New Jersey, United States
Rutgers Cancer Institute of New JerseyRecruiting
New Brunswick, New Jersey, United States
Hematology-Oncology Associates of CNYCompleted
East Syracuse, New York, United States
Novant Health 1Completed
Charlotte, North Carolina, United States
Novant HealthCompleted
Winston-Salem, North Carolina, United States
Cleveland Clinic 1Completed
Cleveland, Ohio, United States
Cleveland ClinicCompleted
Cleveland, Ohio, United States
Cleveland Clinic 2Completed
Mayfield Heights, Ohio, United States
Cleveland Clinic 3Completed
Warrensville Heights, Ohio, United States
The Huntsman Cancer InstituteCompleted
Salt Lake City, Utah, United States
Virginia Cancer SpecialistsRecruiting
Fairfax, Virginia, United States
Providence Regional Cancer PartnershipCompleted
Everett, Washington, United States
Virginia Mason Medical CenterCompleted
Seattle, Washington, United States
Swedish Cancer InstituteRecruiting
Seattle, Washington, United States
Fundacao Pio XIIRecruiting
Barretos, Brazil
PERSONAL Oncologia de Precisao e PersonalizadaRecruiting
Belo Horizonte, Brazil
Instituto do Cancer de Londrina Hospital do Cancer de LondrinaRecruiting
Londrina, Brazil
Associacao Hospitalar Moinhos de VentoRecruiting
Porto Alegre, Brazil
Instituto D Or de Pesquisa e Ensino IDORRecruiting
Rio de Janeiro, Brazil
Instituto D Or de Pesquisa e Ensino IDOR 1Recruiting
Salvador, Brazil
Hospital Alemao Oswaldo CruzRecruiting
São Paulo, Brazil
Impar Servicos Hospitalares SA Hospital Nove de JulhoCompleted
São Paulo, Brazil
Fundacao Antonio Prudente A C Camargo Cancer CenterRecruiting
São Paulo, Brazil
Affiliated Hospital of Hebei UniversityCompleted
Baoding, China
Jilin cancer hospitalRecruiting
Changchun, China
Sichuan Cancer HospitalRecruiting
Chengdu, China
West China Hospital Sichuan UniversityRecruiting
Chengdu, China
The First Affiliated Hospital of PLA Army Medical UniversityRecruiting
Chongqing, China
The First Affiliated Hospital Sun Yat sen UniversityRecruiting
Guangzhou, China
The First Affiliated Hospital Zhejiang University College of MedicineRecruiting
Hangzhou, China
Sir Run Run Shaw Hospital Zhejiang University School of MedicineRecruiting
Hangzhou, China
Harbin medical university cancer hospitalRecruiting
Harbin, China
Huizhou Municipal Central HospitalRecruiting
Huizhou, China
Liuzhou people's HospitalCompleted
Liuzhou, China
Fudan University Shanghai Cancer CenterRecruiting
Shanghai, China
Tianjin Medical University General HospitalRecruiting
Tianjin, China
The First Affiliated Hospital of Wenzhou Medical UniversityRecruiting
Wenzhou, China
Union Hospital Tongji Medical College of Huazhong University of Science and TechnologyRecruiting
Wuhan, China
Hospital of Jiangnan UniversityCompleted
Wuxi, China
The First Affiliated Hospital of Xian Jiaotong UniversityRecruiting
Xi'an, China
Yantai Yuhuangding HospitalCompleted
Yantai, China
Centre Francois BaclesseRecruiting
Caen, France
Centre Georges-François LeclercCompleted
Dijon, France
Institut de Cancérologie du GardRecruiting
Nîmes, France
Institut CurieRecruiting
Paris, France
Institut de cancerologie de l'ouestRecruiting
Saint-Herblain, France
Gustave RoussyRecruiting
Villejuif, France
Evangelische Lungenklinik BerlinCompleted
Berlin, Germany
Universitaetsklinikum KoelnRecruiting
Cologne, Germany
LungenClinic Grosshansdorf GmbHRecruiting
Grosshandorf, Germany
Lungenfachklinik ImmenhausenRecruiting
Immenhausen, Germany
Klinikum Würzburg Mitte gGmbH Standort MissioklinikRecruiting
Würzburg, Germany
Rambam Medical CenterRecruiting
Haifa, Israel
Shaare Zedek Medical CenterRecruiting
Jerusalem, Israel
Meir Medical CenterCompleted
Kfar Saba, Israel
Rabin Medical CenterRecruiting
Petah Tikva, Israel
Sheba Medical CenterRecruiting
Ramat Gan, Israel
Policlinico Hospital San Martino- IRCCS for OncologyRecruiting
Genova, Italy
Ospedale San RaffaeleRecruiting
Milan, Italy
ASST Grande Ospedale Metropolitano NiguardaRecruiting
Milan, Italy
Azienda Ospedaliera San GerardoRecruiting
Monza, Italy
Azienda Ospedaliera Specialistica dei ColliRecruiting
Naples, Italy
National Hospital Organization Himeji Medical CenterActive Not Recruiting
Himeji, Japan
Saiseikai Matsusaka Municipal HospitalActive Not Recruiting
Matsusaka, Japan
Niigata Cancer Center HospitalActive Not Recruiting
Niigata, Japan
Shizuoka Cancer CenterActive Not Recruiting
Shizuoka, Japan
The Cancer Institute Hospital of JFCRActive Not Recruiting
Tokyo, Japan
Wakayama Medical University HospitalActive Not Recruiting
Wakayama, Japan
University Malaya Medical CentreRecruiting
Kuala Lumpur, Malaysia
Hospital Tengku Ampuan AfzanRecruiting
Kuantan, Malaysia
Hospital Umum SarawakRecruiting
Kuching, Malaysia
Beacon Hospital Sdn BhdRecruiting
Petaling Jaya, Malaysia
National Cancer CenterRecruiting
Goyang-si, South Korea
Seoul National University Bundang HospitalRecruiting
Seongnam-si, South Korea
Seoul National University HospitalRecruiting
Seoul, South Korea
Severance Hospital Yonsei University Health SystemRecruiting
Seoul, South Korea
Asan Medical CenterCompleted
Seoul, South Korea
Hosp Univ A CorunaRecruiting
A Coruña, Spain
General University Hospital of AlicantetRecruiting
Alicante, Spain
Hosp. Del MarRecruiting
Barcelona, Spain
Hosp. de La Santa Creu I Sant PauRecruiting
Barcelona, Spain
Hosp Univ Vall D HebronRecruiting
Barcelona, Spain
Inst. Cat. Doncologia-H Duran I ReynalsRecruiting
Barcelona, Spain
Hosp. Gral. Univ. Gregorio MaranonRecruiting
Madrid, Spain
Hosp. Univ. Ramon Y CajalRecruiting
Madrid, Spain
Hosp. Univ. 12 de OctubreRecruiting
Madrid, Spain
Hosp. Univ. La PazRecruiting
Madrid, Spain
Hosp Regional Univ de MalagaRecruiting
Málaga, Spain
Hosp. Virgen MacarenaRecruiting
Seville, Spain
Hosp. Clinico Univ. de ValenciaRecruiting
Valencia, Spain
Hosp. Gral. Univ. ValenciaRecruiting
Valencia, Spain
Cheltenham General HospitalCompleted
Cheltenham, United Kingdom
Torbay Hospital-DevonRecruiting
Devon, United Kingdom
Edinburgh Cancer Centre Western GeneralRecruiting
Edinburgh, United Kingdom
Leicester Royal InfirmaryRecruiting
Leicester, United Kingdom
University College London HospitalsRecruiting
London, United Kingdom
Nottingham City HospitalRecruiting
Nottingham, United Kingdom
Queen Alexandra HospitalRecruiting
Portsmouth, United Kingdom