Amivantamab: Participants will receive amivantamab intravenously.
Osimertinib: Participants will receive osimertinib capsules orally.
Lazertinib: Participants will receive lazertinib tablets orally.
Placebo: Participants will receive matching placebo orally.
Study summary
The purpose of this study is to assess the efficacy of the amivantamab and lazertinib combination, compared with osimertinib, in participants with epidermal growth factor receptor (EGFR) mutation (Exon 19 deletions \[Exon 19del\] or Exon 21 L858R substitution) positive, locally advanced or metastatic non-small cell lung cancer (NSCLC).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Participant must have newly diagnosed histologically or cytologically confirmed, locally advanced or metastatic non-small cell lung cancer (NSCLC) that is treatment naive and not amenable to curative therapy including surgical resection or chemoradiation
* The tumor harbors exon 19 deletions (Exon 19del) or Exon 21 L858R substitution, as detected by an food and drug administration (FDA)-approved or other validated test 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) in accordance with site standard of care
* Mandatory submission of unstained tissue from tumor (in a quantity sufficient to allow for central analysis of EGFR mutation status and blood (for circulating tumor deoxyribonucleic acid \[ctDNA\], digital droplet polymerase chain reaction \[ddPCR\], and pharmacogenomic analysis)
* Any toxicities from prior anticancer therapy must have resolved to common terminology criteria for adverse events (CTCAE) Grade 1 or baseline level
* Participant must have at least 1 measurable lesion, according to response evaluation criteria in solid tumors (RECIST) v1.1 that has not been previously irradiated. Measurable lesions should not have been biopsied during screening, but if only 1 non-irradiated measurable lesion exists, it may undergo a diagnostic biopsy and be acceptable as a target lesion, provided the baseline tumor assessment scans are performed at least 14 days after the biopsy
Exclusion Criteria:
* Participant has received any prior systemic treatment at any time for locally advanced Stage III or metastatic Stage IV disease (adjuvant or neoadjuvant therapy for Stage I or II disease is allowed, if administered more than 12 months prior to the development of locally advanced or metastatic disease)
* Participant has an active or past medical history of leptomeningeal disease
* Participant with untreated spinal cord compression. A participant that has been definitively treated with surgery or radiation and has a stable neurological status for at least 2 weeks prior to randomization is eligible provided they are off corticosteroid treatment or receiving low-dose corticosteroid treatment less than or equal to (\<=) 10 milligrams per day (mg/day) prednisone or equivalent
* Participant has an active or past medical history of interstitial lung disease (ILD)/pneumonitis, including drug-induced or radiation ILD/pneumonitis
* Participant has known allergy, hypersensitivity, or intolerance to the excipients used in formulation of amivantamab, lazertinib, or osimertinib, or any contraindication to the use of osimertinib
* Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study
Primary outcome measure(s)
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR) — From randomization to either disease progression or death whichever occurs first (up to 32.8 months) PFS was defined as the time from randomization until the date of objective disease progression based on BICR using RECIST version 1.1 or death (by any cause) the absence of progression, whichever came first. Disease progression was defined using RECIST 1.1 as a 20 percent (%) increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 millimeters (mL). Participants who have not progressed or have not died at the time of analysis were censored at the time of the latest date of their last evaluable RECIST version 1.1 assessment.
Trial sites (269)
Facility
City
Region
Status
Arizona Oncology Associates, PC - HAL
Goodyear
Arizona
Yuma Regional Medical Center
Yuma
Arizona
City of Hope Long Beach Elm
Long Beach
California
University of California Irvine
Orange
California
Rocky Mountain Cancer Centers
Lone Tree
Colorado
Cancer Specialists of North Florida
Jacksonville
Florida
University Cancer And Blood Center LLC
Athens
Georgia
East Jefferson General Hospital
Metairie
Louisiana
Maryland Oncology Hematology, PA
Columbia
Maryland
Henry Ford Hospital
Detroit
Michigan
Minnesota Oncology Hematology P A
Edina
Minnesota
Mayo Clinic
Rochester
Minnesota
Washington University School Of Medicine
St Louis
Missouri
Astera Cancer Care
East Brunswick
New Jersey
Willamette Valley Cancer Institute and Research Center
Eugene
Oregon
University of Pittsburgh Medical Center
Pittsburgh
Pennsylvania
Sarah Cannon Research Institute
Nashville
Tennessee
Texas Oncology P A
Austin
Texas
Oncology Consultants Texas
Houston
Texas
Virginia Cancer Specialists
Fairfax
Virginia
Centro Oncológico Korben
Buenos Aires
Argentina
Instituto Alexander Fleming
Buenos Aires
Argentina
Hospital Privado Centro Medico de Cordoba
Córdoba
Argentina
Centro Oncologico Riojano Integral (Cori)
La Rioja
Argentina
Clínica Viedma
Viedma
Argentina
Flinders Medical Centre
Bedford Park
Australia
Austin Hospital
Heidelberg
Australia
Cabrini Medical Centre
Malvern
Australia
St John of God Hospital Murdoch
Murdoch
Australia
Sir Charles Gairdner Hospital
Nedlands
Australia
Westmead Hospital
Westmead
Australia
Southern Medical Day Care Centre
Wollongong
Australia
Princess Alexandra Hospital
Woolloongabba
Australia
Cliniques Universitaires Saint Luc
Brussels
Belgium
Grand Hopital De Charleroi Site Les Viviers
Charleroi
Belgium
UZ Leuven
Leuven
Belgium
Clinique Saint Pierre
Ottignies
Belgium
Algemeen Ziekenhuis Delta
Roeselare
Belgium
Fundacao Pio XII
Barretos
Brazil
Cetus Oncologia
Belo Horizonte
Brazil
+ 229 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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