Clinical trial NCT05498428: A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Carcinoma, Non-small-Cell Lung
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2022-08-12
Enrollment: 390
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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: 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. Female participants 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

Primary outcomes:
measure: All Cohorts Except Cohort 4: Objective Response Rate (ORR) Based on Investigator Assessment (INV)
timeFrame: Up to 1 year 6 months
measure: Cohort 4: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 1 year 6 months
measure: Cohort 4: Number of Participants with AEs by Severity
timeFrame: Up to 1 year 6 months
measure: Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values
timeFrame: Up to 1 year 6 months
measure: Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values by Severity
timeFrame: Up to 1 year 6 months
Secondary outcomes:
measure: All Cohorts Except Cohort 4: Number of Participants with AEs
timeFrame: Up to 1 year 6 months
measure: All Cohorts Except Cohort 4: Number of Participants with AEs by Severity
timeFrame: Up to 1 year 6 months
measure: All Cohorts Except Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values
timeFrame: Up to 1 year 6 months
measure: All Cohorts Except Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values by Severity
timeFrame: Up to 1 year 6 months
measure: All Cohorts Except Cohort 4: ORR Based on Independent Central Review (ICR)
timeFrame: Up to 1 year 6 months
measure: All Cohorts Except Cohort 4: Duration of Response (DoR) Based on Investigator Assessment (INV)
timeFrame: Up to 1 year 6 months
measure: All Cohorts Except Cohort 4: Time to Response (TTR) Based on INV
timeFrame: Up to 1 year 6 months
measure: All Cohorts Except Cohort 4: Clinical Benefit Rate (CBR)
timeFrame: Up to 1 year 6 months
measure: All Cohorts Except Cohort 4: Progression-free Survival (PFS)
timeFrame: Up to 1 year 6 months
measure: All Cohorts Except Cohort 4: Overall Survival (OS)
timeFrame: Up to 1 year 6 months
measure: All Cohorts Except Cohort 4: Number of Participants with Venous Thromboembolic Events (VTE)
timeFrame: Up to 1 year 6 months
measure: All Cohorts Except Cohort 4: Number of Participants with Venous Thromboembolic Events (VTE) by Severity
timeFrame: Up to 1 year 6 months
measure: All Cohorts Except Cohort 4: Serum Concentration Immediately Prior to the Next Dose Administration (Ctrough) of Amivantamab
timeFrame: Cycle 2 Day 1 of 28-day cycle
measure: Cohort 4: Cancer Therapy Satisfaction as Assessed by Modified Therapy Administration Satisfaction Questionnaire - Intravenous (TASQ-IV)
timeFrame: Up to 1 year 6 months
measure: Cohort 4: Cancer Therapy Satisfaction as Assessed by Modified Therapy Administration Satisfaction Questionnaire - Subcutaneous (TASQ-SC)
timeFrame: Up to 1 year 6 months
measure: Cohort 4: Patient-reported Status as Assessed by Patient Global Impression of Change (PGIC) Scale Score
timeFrame: Up to 1 year 6 months
measure: Cohort 4: Patient-reported Status as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score
timeFrame: Up to 1 year 6 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California at San Diego
state: California
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute
state: California
city: Washington
country: United States
facility: Johns Hopkins Office of Capital Region Research - Sibley Memorial Hospital
state: District of Columbia
city: Boca Raton
country: United States
facility: Baptist Lynn Cancer Institute
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Orlando
country: United States
facility: AdventHealth
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer & Research Institute
state: Florida
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Baltimore
country: United States
facility: Sidney Kimmel Cancer Center - Bayview Campus
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: East Syracuse
country: United States
facility: Hematology-Oncology Associates of CNY
state: New York
city: Charlotte
country: United States
facility: Novant Health
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Mayfield Heights
country: United States
facility: Cleveland Clinic
state: Ohio
city: Warrensville Heights
country: United States
facility: Cleveland Clinic
state: Ohio
city: Salt Lake City
country: United States
facility: The Huntsman Cancer Institute
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Everett
country: United States
facility: Providence Regional Cancer Partnership
state: Washington
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Barretos
country: Brazil
facility: Fundacao Pio XII
city: Belo Horizonte
country: Brazil
facility: PERSONAL Oncologia de Precisao e Personalizada
city: Londrina
country: Brazil
facility: Instituto do Cancer de Londrina Hospital do Cancer de Londrina
city: Porto Alegre
country: Brazil
facility: Associacao Hospitalar Moinhos de Vento
city: Rio de Janeiro
country: Brazil
facility: Instituto D Or de Pesquisa e Ensino IDOR
city: Salvador
country: Brazil
facility: Instituto D Or de Pesquisa e Ensino IDOR
city: Sao Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
city: Sao Paulo
country: Brazil
facility: Impar Servicos Hospitalares SA Hospital Nove de Julho
city: Sao Paulo
country: Brazil
facility: Fundacao Antonio Prudente A C Camargo Cancer Center
city: Bao Ding Shi
country: China
facility: Affiliated Hospital of Hebei University
city: Changchun
country: China
facility: Jilin cancer hospital
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
city: Chengdu
country: China
facility: West China Hospital Sichuan University
city: ChongQing
country: China
facility: The First Affiliated Hospital of PLA Army Medical University
city: Guangzhou
country: China
facility: The First Affiliated Hospital Sun Yat sen University
city: Hangzhou
country: China
facility: The First Affiliated Hospital Zhejiang University College of Medicine
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital Zhejiang University School of Medicine
city: Harbin
country: China
facility: Harbin medical university cancer hospital
city: Huizhou
country: China
facility: Huizhou Municipal Central Hospital
city: Liuzhou
country: China
facility: Liuzhou people's Hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College of Huazhong University of Science and Technology
city: Wuxi
country: China
facility: Hospital of Jiangnan University
city: XI An
country: China
facility: The First Affiliated Hospital of Xian Jiaotong University
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
city: Caen Cedex 05
country: France
facility: Centre Francois Baclesse
city: Dijon
country: France
facility: Centre Georges-François Leclerc
city: Nîmes
country: France
facility: Institut de Cancérologie du Gard
city: PARIS Cedex 5
country: France
facility: Institut Curie
city: Saint-Herblain Cedex
country: France
facility: Institut de cancerologie de l'ouest
city: Villejuif Cedex
country: France
facility: Gustave Roussy
city: Berlin
country: Germany
facility: Evangelische Lungenklinik Berlin
city: Grosshandorf
country: Germany
facility: LungenClinic Grosshansdorf GmbH
city: Immenhausen
country: Germany
facility: Lungenfachklinik Immenhausen
city: Koeln
country: Germany
facility: Universitaetsklinikum Koelnt
city: Wuerzburg
country: Germany
facility: Klinikum Würzburg Mitte gGmbH Standort Missioklinik
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Genova
country: Italy
facility: Policlinico Hospital San Martino- IRCCS for Oncology
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo
city: Naples
country: Italy
facility: Azienda Ospedaliera Specialistica dei Colli
city: Himeji
country: Japan
facility: National Hospital Organization Himeji Medical Center
city: Matsusaka
country: Japan
facility: Matsusaka Municipal Hospital
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Wakayama
country: Japan
facility: Wakayama Medical University Hospital
city: Goyang-Si
country: Korea, Republic of
facility: National Cancer Center
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan
city: Kuching
country: Malaysia
facility: Hospital Umum Sarawak
city: Petaling Jaya
country: Malaysia
facility: Beacon Hospital Sdn Bhd
city: A Coruña
country: Spain
facility: Hosp Univ A Coruna
city: Alacant
country: Spain
facility: General University Hospital of Alicantet
city: Barcelona
country: Spain
facility: Hosp. Del Mar
city: Barcelona
country: Spain
facility: Hosp. de La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Barcelona
country: Spain
facility: Inst. Cat. Doncologia-H Duran I Reynals
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Maranon
city: Madrid
country: Spain
facility: Hosp. Univ. Ramon Y Cajal
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Madrid
country: Spain
facility: Hosp. Univ. La Paz
city: Malaga
country: Spain
facility: Hosp Regional Univ de Malaga
city: Sevilla
country: Spain
facility: Hosp. Virgen Macarena
city: Valencia
country: Spain
facility: Hosp. Clinico Univ. de Valencia
city: Valencia
country: Spain
facility: Hosp. Gral. Univ. Valencia
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
city: Devon
country: United Kingdom
facility: Torbay Hospital-Devon
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre Western General
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: University College London Hospitals
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: