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NCT05498428PHASE2Recruiting

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

Janssen Research & Development, LLC

Start Date

11/11/2022

Completion Date

8/18/2028

Summary

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

Age Range: 18 years to No maximum

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

Interventions

DRUG

Amivantamab

DRUG

Lazertinib

DRUG

Carboplatin

DRUG

Pemetrexed

DRUG

Direct Oral Anticoagulant (DOAC)

DRUG

Low Molecular Weight Heparin (LMWH)

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Conditions

Carcinoma, Non-small-Cell Lung

Locations

University of California at San Diego

La Jolla, California 92093

United States

University of California Irvine

Orange, California 92868

United States

Stanford Cancer Institute

Stanford, California 94305

United States

Johns Hopkins Office of Capital Region Research - Sibley Memorial Hospital

Washington D.C., District of Columbia 20016

United States

Baptist Lynn Cancer Institute

Boca Raton, Florida 33486

United States

Mount Sinai Medical Center

Miami Beach, Florida 33140

United States

AdventHealth

Orlando, Florida 32804

United States

H. Lee Moffitt Cancer & Research Institute

Tampa, Florida 33612

United States

University of Kansas Cancer Center

Westwood, Kansas 66205

United States

Sidney Kimmel Cancer Center - Bayview Campus

Baltimore, Maryland 21224

United States

Boston Medical Center

Boston, Massachusetts 02118

United States

Washington University School Of Medicine

St Louis, Missouri 63110

United States

Hackensack University Medical Center

Hackensack, New Jersey 07601

United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey 08901

United States

Hematology-Oncology Associates of CNY

East Syracuse, New York 13057

United States

Novant Health 1

Charlotte, North Carolina 28204

United States

Novant Health

Winston-Salem, North Carolina 27106

United States

Cleveland Clinic 1

Cleveland, Ohio 44111

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

Cleveland Clinic 2

Mayfield Heights, Ohio 44124

United States

Cleveland Clinic 3

Warrensville Heights, Ohio 44122

United States

The Huntsman Cancer Institute

Salt Lake City, Utah 84112

United States

Virginia Cancer Specialists

Fairfax, Virginia 22031

United States

Providence Regional Cancer Partnership

Everett, Washington 98201

United States

Virginia Mason Medical Center

Seattle, Washington 98101

United States

Swedish Cancer Institute

Seattle, Washington 98104

United States

Fundacao Pio XII

Barretos, 14784-400

Brazil

PERSONAL Oncologia de Precisao e Personalizada

Belo Horizonte, 30130 090

Brazil

Instituto do Cancer de Londrina Hospital do Cancer de Londrina

Londrina, 86015

Brazil

Associacao Hospitalar Moinhos de Vento

Porto Alegre, 90035-001

Brazil

Instituto D Or de Pesquisa e Ensino IDOR

Rio de Janeiro, 22281 100

Brazil

Instituto D Or de Pesquisa e Ensino IDOR 1

Salvador, 41253-190

Brazil

Hospital Alemao Oswaldo Cruz

São Paulo, 01327 001

Brazil

Impar Servicos Hospitalares SA Hospital Nove de Julho

São Paulo, 01409-001

Brazil

Fundacao Antonio Prudente A C Camargo Cancer Center

São Paulo, 01509 900

Brazil

Affiliated Hospital of Hebei University

Baoding, 071051

China

Jilin cancer hospital

Changchun, 130000

China

Sichuan Cancer Hospital

Chengdu, 610041

China

West China Hospital Sichuan University

Chengdu, 610047

China

The First Affiliated Hospital of PLA Army Medical University

Chongqing, 400038

China

The First Affiliated Hospital Sun Yat sen University

Guangzhou, 510060

China

The First Affiliated Hospital Zhejiang University College of Medicine

Hangzhou, 310003

China

Sir Run Run Shaw Hospital Zhejiang University School of Medicine

Hangzhou, 310016

China

Harbin medical university cancer hospital

Harbin, 150000

China

Huizhou Municipal Central Hospital

Huizhou, 516001

China

Liuzhou people's Hospital

Liuzhou, 545006

China

Fudan University Shanghai Cancer Center

Shanghai, 200032

China

Tianjin Medical University General Hospital

Tianjin, 300052

China

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, 325000

China

Union Hospital Tongji Medical College of Huazhong University of Science and Technology

Wuhan, 430022

China

Hospital of Jiangnan University

Wuxi, 214122

China

The First Affiliated Hospital of Xian Jiaotong University

Xi'an, 710061

China

Yantai Yuhuangding Hospital

Yantai, 264000

China

Centre Francois Baclesse

Caen, 14076

France

Centre Georges-François Leclerc

Dijon, 21079

France

Institut de Cancérologie du Gard

Nîmes, 30029

France

Institut Curie

Paris, 75248

France

Institut de cancerologie de l'ouest

Saint-Herblain, 44805

France

Gustave Roussy

Villejuif, 94800

France

Evangelische Lungenklinik Berlin

Berlin, 13125

Germany

Universitaetsklinikum Koeln

Cologne, 50937

Germany

LungenClinic Grosshansdorf GmbH

Grosshandorf, 22927

Germany

Lungenfachklinik Immenhausen

Immenhausen, 34376

Germany

Klinikum Würzburg Mitte gGmbH Standort Missioklinik

Würzburg, 97074

Germany

Rambam Medical Center

Haifa, 3109601

Israel

Shaare Zedek Medical Center

Jerusalem, 9103102

Israel

Meir Medical Center

Kfar Saba, 44281

Israel

Rabin Medical Center

Petah Tikva, 4941492

Israel

Sheba Medical Center

Ramat Gan, 52621

Israel

Policlinico Hospital San Martino- IRCCS for Oncology

Genova, 16132

Italy

Ospedale San Raffaele

Milan, 20132

Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162

Italy

Azienda Ospedaliera San Gerardo

Monza, 20090

Italy

Azienda Ospedaliera Specialistica dei Colli

Naples, 80131

Italy

National Hospital Organization Himeji Medical Center

Himeji, 670-8520

Japan

Saiseikai Matsusaka Municipal Hospital

Matsusaka, 515 8544

Japan

Niigata Cancer Center Hospital

Niigata, 951-8566

Japan

Shizuoka Cancer Center

Shizuoka, 411 8777

Japan

The Cancer Institute Hospital of JFCR

Tokyo, 135 8550

Japan

Wakayama Medical University Hospital

Wakayama, 641 8510

Japan

University Malaya Medical Centre

Kuala Lumpur, 59100

Malaysia

Hospital Tengku Ampuan Afzan

Kuantan, 25100

Malaysia

Hospital Umum Sarawak

Kuching, 93586

Malaysia

Beacon Hospital Sdn Bhd

Petaling Jaya, 46050

Malaysia

National Cancer Center

Goyang-si, 10408

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

Hosp Univ A Coruna

A Coruña, 15006

Spain

General University Hospital of Alicantet

Alicante, 03010

Spain

Hosp. Del Mar

Barcelona, 08003

Spain

Hosp. de La Santa Creu I Sant Pau

Barcelona, 08025

Spain

Hosp Univ Vall D Hebron

Barcelona, 08035

Spain

Inst. Cat. Doncologia-H Duran I Reynals

Barcelona, 8908

Spain

Hosp. Gral. Univ. Gregorio Maranon

Madrid, 28007

Spain

Hosp. Univ. Ramon Y Cajal

Madrid, 28034

Spain

Hosp. Univ. 12 de Octubre

Madrid, 28041

Spain

Hosp. Univ. La Paz

Madrid, 28046

Spain

Hosp Regional Univ de Malaga

Málaga, 29010

Spain

Hosp. Virgen Macarena

Seville, 41009

Spain

Hosp. Clinico Univ. de Valencia

Valencia, 46010

Spain

Hosp. Gral. Univ. Valencia

Valencia, 46014

Spain

Cheltenham General Hospital

Cheltenham, GL53 7AN

United Kingdom

Torbay Hospital-Devon

Devon, TQ2 7AA

United Kingdom

Edinburgh Cancer Centre Western General

Edinburgh, EH4 2XU

United Kingdom

Leicester Royal Infirmary

Leicester, LE1 5WW

United Kingdom

University College London Hospitals

London, NW1 2PG

United Kingdom

Nottingham City Hospital

Nottingham, NG5 1PB

United Kingdom

Queen Alexandra Hospital

Portsmouth, PO6 3LY

United Kingdom