Sponsor: Janssen Research & Development, LLC (industry)
Phase: 2
Start date: Nov. 11, 2022
Planned enrollment: 390
Last updated in HealthScout: Dec 2024
No investigational drugs.
Last updated: Apr 2025
Goal: The trial aims to evaluate the anti-tumor efficacy and safety profile of subcutaneous amivantamab, a monoclonal antibody against EGFR and MET, using a recombinant human hyaluronidase (rHuPH20) co-formulation across various dosing regimens in patients with advanced or metastatic solid tumors, including non-small cell lung cancer (NSCLC) with specific EGFR mutations. Additionally, it seeks to assess the safety of transitioning patients from amivantamab IV to its subcutaneous formulation.
Patients: The trial focuses on participants with locally advanced or metastatic NSCLC possessing specific EGFR mutations such as exon 19 deletions, exon 21 L858R substitutions, or exon 20 insertions. Patients are categorized into different cohorts based on prior treatment histories, including those who are treatment-naïve, post-osimertinib, or previously treated with amivantamab IV.
Design: This is a phase 2, open-label, non-randomized, parallel cohort study with a planned enrollment of 390 participants across multiple treatment arms. Each cohort follows a specific treatment regimen based on their EGFR mutation status and line of therapy.
Treatments: The study investigates amivantamab in subcutaneous co-formulation as a monotherapy and in combination with other agents, such as lazertinib and chemotherapeutics carboplatin and pemetrexed. Amivantamab is a bispecific fully human IgG1 antibody targeting EGFR and MET pathways, intended to inhibit tumor growth by blocking receptor signaling and mediating antibody-dependent cellular cytotoxicity. Previous trials have demonstrated efficacy in treatment-resistant NSCLC with manageable safety profiles. In certain cohorts, it is combined with lazertinib, another targeted therapy, to enhance therapeutic effects. Regimens are adjusted based on cohorts and previous therapies received.
Outcomes: Primary outcomes include objective response rate (ORR) for all cohorts except for those solely investigating safety in previously exposed patients, where adverse events are the primary focus. Secondary outcomes measure the duration of response (DoR), progression-free survival (PFS), overall survival (OS), and patient-reported satisfaction and quality of life assessments, specifically for patients transitioning from IV to subcutaneous administration.
Burden on patient: The trial places a moderate to high burden on patients due to frequent administration schedules, combination therapies, and regular clinical evaluations. Participants are subject to multiple cycles of treatment, each involving frequent clinic visits for drug administration, and routine imaging and laboratory assessments to monitor disease progression and side effects. Patients transitioning from IV to subcutaneous therapy might endure additional visits and questionnaires assessing treatment satisfaction.
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
Belo Horizonte, 30130 090, Brazil
No email / No phone
Status: Recruiting
Sao Paulo, 01509 900, Brazil
No email / No phone
Status: Recruiting
Sao Paulo, 01409-001, Brazil
No email / No phone
Status: Recruiting
Sao Paulo, 01327 001, Brazil
No email / No phone
Status: Recruiting
Salvador, 41253-190, Brazil
No email / No phone
Status: Recruiting
Rio de Janeiro, 22281 100, Brazil
No email / No phone
Status: Recruiting
Porto Alegre, 90035-001, Brazil
No email / No phone
Status: Recruiting
Londrina, 86015, Brazil
No email / No phone
Status: Recruiting
Barretos, 14784-400, Brazil
No email / No phone
Status: Recruiting
Huizhou, 516001, China
No email / No phone
Status: Recruiting
Harbin, 150000, China
No email / No phone
Status: Recruiting
Hangzhou, 310016, China
No email / No phone
Status: Recruiting
Hangzhou, 310003, China
No email / No phone
Status: Recruiting
Guangzhou, 510060, China
No email / No phone
Status: Recruiting
ChongQing, 400038, China
No email / No phone
Status: Recruiting
Chengdu, 610047, China
No email / No phone
Status: Recruiting
Chengdu, 610041, China
No email / No phone
Status: Recruiting
Changchun, 130000, China
No email / No phone
Status: Recruiting
Bao Ding Shi, 071051, China
No email / No phone
Status: Recruiting
Yantai, 264000, China
No email / No phone
Status: Completed
XI An, 710061, China
No email / No phone
Status: Recruiting
Wuxi, 214122, China
No email / No phone
Status: Completed
Wuhan, 430022, China
No email / No phone
Status: Recruiting
Wenzhou, 325000, China
No email / No phone
Status: Recruiting
Tianjin, 300052, China
No email / No phone
Status: Recruiting
Shanghai, 200032, China
No email / No phone
Status: Recruiting
Liuzhou, 545006, China
No email / No phone
Status: Completed
Nîmes, 30029, France
No email / No phone
Status: Recruiting
Caen Cedex 05, 14076, France
No email / No phone
Status: Recruiting
Dijon, 21079, France
No email / No phone
Status: Completed
PARIS Cedex 5, 75248, France
No email / No phone
Status: Recruiting
Saint-Herblain Cedex, 44805, France
No email / No phone
Status: Recruiting
Villejuif Cedex, 94800, France
No email / No phone
Status: Recruiting
Immenhausen, 34376, Germany
No email / No phone
Status: Recruiting
Grosshandorf, 22927, Germany
No email / No phone
Status: Recruiting
Wuerzburg, 97074, Germany
No email / No phone
Status: Recruiting
Berlin, 13125, Germany
No email / No phone
Status: Completed
Koeln, 50937, Germany
No email / No phone
Status: Recruiting
Ramat Gan, 52621, Israel
No email / No phone
Status: Recruiting
Petah Tikva, 4941492, Israel
No email / No phone
Status: Recruiting
Kfar Saba, 44281, Israel
No email / No phone
Status: Recruiting
Jerusalem, 9103102, Israel
No email / No phone
Status: Recruiting
Haifa, 3109601, Israel
No email / No phone
Status: Recruiting
Genova, 16132, Italy
No email / No phone
Status: Recruiting
Milano, 20132, Italy
No email / No phone
Status: Recruiting
Milano, 20162, Italy
No email / No phone
Status: Recruiting
Monza, 20090, Italy
No email / No phone
Status: Recruiting
Naples, 80131, Italy
No email / No phone
Status: Recruiting
Matsusaka, 515-8544, Japan
No email / No phone
Status: ACTIVE_NOT_RECRUITING
Niigata, 951-8566, Japan
No email / No phone
Status: ACTIVE_NOT_RECRUITING
Shizuoka, 411 8777, Japan
No email / No phone
Status: ACTIVE_NOT_RECRUITING
Wakayama, 641 8510, Japan
No email / No phone
Status: ACTIVE_NOT_RECRUITING
Tokyo, 135 8550, Japan
No email / No phone
Status: ACTIVE_NOT_RECRUITING
Himeji, 670-8520, Japan
No email / No phone
Status: ACTIVE_NOT_RECRUITING
Seongnam-si, 13620, Korea, Republic of
No email / No phone
Status: Recruiting
Seoul, 03722, Korea, Republic of
No email / No phone
Status: Recruiting
Seoul, 03080, Korea, Republic of
No email / No phone
Status: Recruiting
Seoul, 05505, Korea, Republic of
No email / No phone
Status: Recruiting
Goyang-Si, 10408, Korea, Republic of
No email / No phone
Status: Recruiting
Petaling Jaya, 46050, Malaysia
No email / No phone
Status: Recruiting
Kuching, 93586, Malaysia
No email / No phone
Status: Recruiting
Kuantan, 25100, Malaysia
No email / No phone
Status: Recruiting
Kuala Lumpur, 59100, Malaysia
No email / No phone
Status: Recruiting
Madrid, 28034, Spain
No email / No phone
Status: Recruiting
A Coruña, 15006, Spain
No email / No phone
Status: Recruiting
Alacant, 03010, Spain
No email / No phone
Status: Recruiting
Barcelona, 08003, Spain
No email / No phone
Status: Recruiting
Barcelona, 08025, Spain
No email / No phone
Status: Recruiting
Barcelona, 08035, Spain
No email / No phone
Status: Recruiting
Barcelona, 8908, Spain
No email / No phone
Status: Recruiting
Madrid, 28007, Spain
No email / No phone
Status: Recruiting
Madrid, 28041, Spain
No email / No phone
Status: Recruiting
Madrid, 28046, Spain
No email / No phone
Status: Recruiting
Malaga, 29010, Spain
No email / No phone
Status: Recruiting
Sevilla, 41009, Spain
No email / No phone
Status: Recruiting
Valencia, 46010, Spain
No email / No phone
Status: Recruiting
Valencia, 46014, Spain
No email / No phone
Status: Recruiting
Devon, TQ2 7AA, United Kingdom
No email / No phone
Status: Recruiting
Cheltenham, GL53 7AN, United Kingdom
No email / No phone
Status: Completed
Portsmouth, PO6 3LY, United Kingdom
No email / No phone
Status: Recruiting
Nottingham, NG5 1PB, United Kingdom
No email / No phone
Status: Recruiting
London, NW1 2PG, United Kingdom
No email / No phone
Status: Recruiting
Leicester, LE1 5WW, United Kingdom
No email / No phone
Status: Recruiting
Edinburgh, EH4 2XU, United Kingdom
No email / No phone
Status: Recruiting
La Jolla, California, 92093, United States
No email / No phone
Status: Recruiting
Stanford, California, 94305, United States
No email / No phone
Status: Recruiting
Orange, California, 92868, United States
No email / No phone
Status: Recruiting
Washington, District of Columbia, 20016, United States
No email / No phone
Status: Recruiting
Miami Beach, Florida, 33140, United States
No email / No phone
Status: Recruiting
Orlando, Florida, 32804, United States
No email / No phone
Status: Recruiting
Tampa, Florida, 33612, United States
No email / No phone
Status: Recruiting
Boca Raton, Florida, 33486, United States
No email / No phone
Status: Completed
Westwood, Kansas, 66205, United States
No email / No phone
Status: Recruiting
Baltimore, Maryland, 21224, United States
No email / No phone
Status: Recruiting
Boston, Massachusetts, 02118, United States
No email / No phone
Status: Recruiting
Saint Louis, Missouri, 63110, United States
No email / No phone
Status: Recruiting
New Brunswick, New Jersey, 08901, United States
No email / No phone
Status: Recruiting
Hackensack, New Jersey, 07601, United States
No email / No phone
Status: Recruiting
East Syracuse, New York, 13057, United States
No email / No phone
Status: Completed
Charlotte, North Carolina, 28204, United States
No email / No phone
Status: Recruiting
Winston-Salem, North Carolina, 27106, United States
No email / No phone
Status: Recruiting
Warrensville Heights, Ohio, 44122, United States
No email / No phone
Status: Completed
Mayfield Heights, Ohio, 44124, United States
No email / No phone
Status: Completed
Cleveland, Ohio, 44195, United States
No email / No phone
Status: Completed
Cleveland, Ohio, 44111, United States
No email / No phone
Status: Completed
Salt Lake City, Utah, 84112, United States
No email / No phone
Status: Completed
Fairfax, Virginia, 22031, United States
No email / No phone
Status: Recruiting
Seattle, Washington, 98104, United States
No email / No phone
Status: Recruiting
Everett, Washington, 98201, United States
No email / No phone
Status: Completed
Seattle, Washington, 98101, United States
No email / No phone
Status: Completed