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

Carcinoma, Non-small-Cell Lung Clinical Trial

— PALOMA-2  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05498428
• Other study ID #: CR109264
• Secondary ID: 2022-000526-2161
• Status: Recruiting
• Phase: Phase 2
• Start date: November 11, 2022
• Est. completion date: August 5, 2026

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 390
• Est. completion date: August 5, 2026
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-small-Cell Lung

Intervention

Drug:
• Amivantamab
Amivantamab will be administered subcutaneously by manual injection.
• Lazertinib
Lazertinib will be administered as an oral tablet.
• Carboplatin
Carboplatin will be administrated by IV infusion.
• Pemetrexed
Pemetrexed will be administered by IV infusion.
• Direct Oral Anticoagulant (DOAC)
DOAC will be administered orally.
• Low Molecular Weight Heparin (LMWH)
LMWH will be administered subcutaneously.

Locations

Country	Name	City	State
Brazil	Fundacao Pio XII	Barretos
Brazil	PERSONAL Oncologia de Precisao e Personalizada	Belo Horizonte
Brazil	Instituto do Cancer de Londrina Hospital do Cancer de Londrina	Londrina
Brazil	Associacao Hospitalar Moinhos de Vento	Porto Alegre
Brazil	Instituto D Or de Pesquisa e Ensino (IDOR)	Rio de Janeiro
Brazil	Instituto D Or de Pesquisa e Ensino (IDOR)	Salvador
Brazil	Fundacao Antonio Prudente A C Camargo Cancer Center	Sao Paulo
Brazil	Hospital Alemao Oswaldo Cruz	Sao Paulo
Brazil	Impar Servicos Hospitalares SA - Hospital Nove de Julho	Sao Paulo
China	Affiliated Hospital of Hebei University	Baoding
China	Jilin cancer hospital	Changchun
China	Sichuan Cancer Hospital	Chengdu
China	West China Hospital Sichuan University	Chengdu
China	The First Affiliated Hospital of PLA Army Medical University	ChongQing
China	The First Affiliated Hospital Sun Yat sen University	Guangzhou
China	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou
China	The First Affiliated Hospital Zhejiang University College of Medicine	Hangzhou
China	Harbin medical university cancer hospital	Harbin
China	Huizhou Municipal Central Hospital	Huizhou
China	Liuzhou people's Hospital	Liuzhou
China	Fudan University Shanghai Cancer Center	Shanghai
China	Tianjin Medical University General Hospital	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou
China	Union Hospital Tongji Medical College of Huazhong University of Science and Technology	Wuhan
China	Hospital of Jiangnan University	Wuxi
China	The First Affiliated Hospital of Xian Jiaotong University	XI An
China	Yantai Yuhuangding Hospital	Yantai
France	Centre Francois Baclesse	Caen Cedex 05
France	Centre Georges-François Leclerc	Dijon
France	Institut de Cancérologie du Gard	Nîmes
France	Institut Curie	PARIS Cedex 5
France	Institut de cancerologie de l'ouest	Saint-Herblain Cedex
France	Gustave Roussy	Villejuif Cedex
Germany	Evangelische Lungenklinik Berlin	Berlin
Germany	LungenClinic Grosshansdorf GmbH	Grosshandorf
Germany	Lungenfachklinik Immenhausen	Immenhausen
Germany	Universitaetsklinikum Koelnt	Koeln
Germany	Klinikum Würzburg Mitte gGmbH Standort Missioklinik	Wuerzburg
Israel	Rambam Medical Center Department of Pediatric Pulmonology Meyer Childern's Hospital	Haifa
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Meir Medical Center	Kfar Saba
Israel	Rabin Medical Center	Petah Tikva
Israel	Sheba Medical Center	Ramat Gan
Italy	Policlinico Hospital San Martino- IRCCS for Oncology	Genova
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano
Italy	Ospedale San Raffaele	Milano
Italy	Azienda Ospedaliera San Gerardo	Monza
Italy	Azienda Ospedaliera Specialistica dei Colli	Naples
Japan	National Hospital Organization Himeji Medical Center	Himeji
Japan	Matsusaka Municipal Hospital	Matsusaka
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Shizuoka Cancer Center	Shizuoka
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	Wakayama Medical University Hospital	Wakayama
Korea, Republic of	National Cancer Center	Goyang-Si
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Hospital Tengku Ampuan Afzan	Kuantan
Malaysia	Hospital Umum Sarawak	Kuching
Malaysia	Beacon Hospital Sdn Bhd	Petaling Jaya
Spain	Hosp. Univ. A Coruna	A Coruña
Spain	General University Hospital of Alicantet	Alacant
Spain	Hosp. de La Santa Creu I Sant Pau	Barcelona
Spain	Hosp. Del Mar	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Inst. Cat. Doncologia-H Duran I Reynals	Barcelona
Spain	Hosp. Gral. Univ. Gregorio Maranon	Madrid
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Univ. La Paz	Madrid
Spain	Hosp. Univ. Ramon Y Cajal	Madrid
Spain	Hosp. Regional Univ. de Malaga	Malaga
Spain	Hosp. Virgen Macarena	Sevilla
Spain	Hosp. Clinico Univ. de Valencia	Valencia
Spain	Hosp. Gral. Univ. Valencia	Valencia
United Kingdom	Cheltenham General Hospital	Cheltenham
United Kingdom	Torbay Hospital-Devon	Devon
United Kingdom	Edinburgh Cancer Centre Western General	Edinburgh
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	University College London Hospitals	London
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	Queen Alexandra Hospital	Portsmouth
United States	Baptist Lynn Cancer Institute	Boca Raton	Florida
United States	Boston Medical Center	Boston	Massachusetts
United States	Novant Health	Charlotte	North Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Hemotology Oncology Associates of CNY	East Syracuse	New York
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	University of California at San Diego	La Jolla	California
United States	Cleveland Clinic	Mayfield Heights	Ohio
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	University of California Irvine	Orange	California
United States	AdventHealth	Orlando	Florida
United States	Washington University School Of Medicine	Saint Louis	Missouri
United States	The Huntsman Cancer Institute	Salt Lake City	Utah
United States	Swedish Cancer Institute	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Stanford Cancer Institute	Stanford	California
United States	H. Lee Moffitt Cancer & Research Institute	Tampa	Florida
United States	Cleveland Clinic	Warrensville Heights	Ohio
United States	Johns Hopkins Office of Capital Region Research - Sibley Memorial Hospital	Washington	District of Columbia
United States	University of Kansas Cancer Center	Westwood	Kansas
United States	Novant Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Brazil,  China,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All Cohorts Except Cohort 4: Objective Response Rate (ORR) Based on Investigator Assessment (INV)	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
Primary	Cohort 4: Number of Participants with Adverse Events (AEs)	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
Primary	Cohort 4: Number of Participants with AEs by Severity	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
Primary	Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values	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
Primary	Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values by Severity	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 1 year 6 months
Secondary	All Cohorts Except Cohort 4: Number of Participants with AEs	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
Secondary	All Cohorts Except Cohort 4: Number of Participants with AEs by Severity	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
Secondary	All Cohorts Except Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values	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
Secondary	All Cohorts Except Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values by Severity	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
Secondary	All Cohorts Except Cohort 4: ORR Based on Independent Central Review (ICR)	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
Secondary	All Cohorts Except Cohort 4: Duration of Response (DoR) Based on Investigator Assessment (INV)	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
Secondary	All Cohorts Except Cohort 4: Time to Response (TTR) Based on INV	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
Secondary	All Cohorts Except Cohort 4: Clinical Benefit Rate (CBR)	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
Secondary	All Cohorts Except Cohort 4: Progression-free Survival (PFS)	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 1 year 6 months
Secondary	All Cohorts Except Cohort 4: Overall Survival (OS)	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 1 year 6 months
Secondary	All Cohorts Except Cohort 4: Number of Participants with Venous Thromboembolic Events (VTE)	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
Secondary	All Cohorts Except Cohort 4: Number of Participants with Venous Thromboembolic Events (VTE) by Severity	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
Secondary	All Cohorts Except Cohort 4: Serum Concentration Immediately Prior to the Next Dose Administration (Ctrough) of Amivantamab	Ctrough is defined as the serum concentration of amivantamab immediately prior to the next drug administration.	Cycle 2 Day 1 of 28-day cycle
Secondary	Cohort 4: Cancer Therapy Satisfaction as Assessed by Modified Therapy Administration Satisfaction Questionnaire - Intravenous (TASQ-IV)	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
Secondary	Cohort 4: Cancer Therapy Satisfaction as Assessed by Modified Therapy Administration Satisfaction Questionnaire - Subcutaneous (TASQ-SC)	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
Secondary	Cohort 4: Patient-reported Status as Assessed by Patient Global Impression of Change (PGIC) Scale Score	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
Secondary	Cohort 4: Patient-reported Status as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score	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