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RecruitingInterventionalPhase 2

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

NCT ID: NCT05498428Sponsor: Janssen Research & Development, LLCLast updated: 2026-06-05

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).

Arms & interventions

  • DrugAmivantamab

    Amivantamab will be administered subcutaneously by manual injection.

  • DrugLazertinib

    Lazertinib will be administered as an oral tablet.

  • DrugCarboplatin

    Carboplatin will be administrated by IV infusion.

  • DrugPemetrexed

    Pemetrexed will be administered by IV infusion.

  • DrugDirect Oral Anticoagulant (DOAC)

    DOAC will be administered orally.

  • DrugLow Molecular Weight Heparin (LMWH)

    LMWH will be administered subcutaneously.

Outcome measures

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.

    Time frame: Up to 1 year 6 months

  • 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.

    Time frame: Up to approximately 4 years and 9 months

  • 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.

    Time frame: Up to approximately 4 years and 9 months

  • 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.

    Time frame: Up to approximately 4 years and 9 months

  • 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.

    Time frame: Up to approximately 4 years and 9 months

Secondary

  • All Cohorts Except Cohort 4: Number of Participants with AEs

    Time frame: Up to 1 year 6 months

  • All Cohorts Except Cohort 4: Number of Participants with AEs by Severity

    Time frame: Up to 1 year 6 months

  • All Cohorts Except Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values

    Time frame: Up to 1 year 6 months

  • All Cohorts Except Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values by Severity

    Time frame: Up to 1 year 6 months

  • All Cohorts Except Cohort 4: ORR Based on Independent Central Review (ICR)

    Time frame: Up to 1 year 6 months

  • All Cohorts Except Cohort 4: Duration of Response (DoR) Based on Investigator Assessment (INV)

    Time frame: Up to 1 year 6 months

  • All Cohorts Except Cohort 4: Time to Response (TTR) Based on INV

    Time frame: Up to 1 year 6 months

  • All Cohorts Except Cohort 4: Clinical Benefit Rate (CBR)

    Time frame: Up to 1 year 6 months

  • All Cohorts Except Cohort 4: Progression-free Survival (PFS)

    Time frame: Up to 3 years

  • All Cohorts Except Cohort 4: Overall Survival (OS)

    Time frame: Up to approximately 4 years

  • All Cohorts Except Cohort 4: Number of Participants with Venous Thromboembolic Events (VTE)

    Time frame: Up to 1 year 6 months

  • All Cohorts Except Cohort 4: Number of Participants with Venous Thromboembolic Events (VTE) by Severity

    Time frame: Up to 1 year 6 months

  • All Cohorts Except Cohort 4: Serum Concentration Immediately Prior to the Next Dose Administration (Ctrough) of Amivantamab

    Time frame: Cycle 2 Day 1 of 28-day cycle

  • Cohort 4: Cancer Therapy Satisfaction as Assessed by Modified Therapy Administration Satisfaction Questionnaire - Intravenous (TASQ-IV)

    Time frame: Up to 1 year 6 months

  • Cohort 4: Cancer Therapy Satisfaction as Assessed by Modified Therapy Administration Satisfaction Questionnaire - Subcutaneous (TASQ-SC)

    Time frame: Up to 1 year 6 months

  • Cohort 4: Patient-reported Status as Assessed by Patient Global Impression of Change (PGIC) Scale Score

    Time frame: Up to 1 year 6 months

  • Cohort 4: Patient-reported Status as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score

    Time frame: Up to 1 year 6 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 locations (26)

University of California at San Diego

La Jolla, California, 92093

Recruiting

University of California Irvine

Orange, California, 92868

Recruiting

Stanford Cancer Institute

Stanford, California, 94305

Recruiting

Johns Hopkins Office of Capital Region Research - Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016

Recruiting

Baptist Lynn Cancer Institute

Boca Raton, Florida, 33486

Completed

Mount Sinai Medical Center

Miami Beach, Florida, 33140

Recruiting

AdventHealth

Orlando, Florida, 32804

Recruiting

H. Lee Moffitt Cancer & Research Institute

Tampa, Florida, 33612

Completed

University of Kansas Cancer Center

Westwood, Kansas, 66205

Recruiting

Sidney Kimmel Cancer Center - Bayview Campus

Baltimore, Maryland, 21224

Recruiting

Boston Medical Center

Boston, Massachusetts, 02118

Recruiting

Washington University School Of Medicine

St Louis, Missouri, 63110

Recruiting

Hackensack University Medical Center

Hackensack, New Jersey, 07601

Recruiting

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901

Recruiting

Hematology-Oncology Associates of CNY

East Syracuse, New York, 13057

Completed

Novant Health 1

Charlotte, North Carolina, 28204

Completed

Novant Health

Winston-Salem, North Carolina, 27106

Completed

Cleveland Clinic 1

Cleveland, Ohio, 44111

Completed

Cleveland Clinic

Cleveland, Ohio, 44195

Completed

Cleveland Clinic 2

Mayfield Heights, Ohio, 44124

Completed

Cleveland Clinic 3

Warrensville Heights, Ohio, 44122

Completed

The Huntsman Cancer Institute

Salt Lake City, Utah, 84112

Completed

Virginia Cancer Specialists

Fairfax, Virginia, 22031

Recruiting

Providence Regional Cancer Partnership

Everett, Washington, 98201

Completed

Virginia Mason Medical Center

Seattle, Washington, 98101

Completed

Swedish Cancer Institute

Seattle, Washington, 98104

Recruiting