A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Inclusion Criteria:

• Participant must have newly diagnosed histologically or cytologically confirmed,locally advanced or metastatic non-small cell lung cancer (NSCLC) that is treatmentnaive and not amenable to curative therapy including surgical resection orchemoradiation

• The tumor harbors exon 19 deletions (Exon 19del) or Exon 21 L858R substitution, asdetected by an food and drug administration (FDA)-approved or other validated testin a clinical laboratory improvement amendments (CLIA) certified laboratory (sitesin the United states [US]) or an accredited local laboratory (sites outside of theUS) in accordance with site standard of care

• Mandatory submission of unstained tissue from tumor (in a quantity sufficient toallow for central analysis of EGFR mutation status and blood (for circulating tumordeoxyribonucleic acid [ctDNA], digital droplet polymerase chain reaction [ddPCR],and pharmacogenomic analysis)

• Any toxicities from prior anticancer therapy must have resolved to commonterminology criteria for adverse events (CTCAE) Grade 1 or baseline level

• Participant must have at least 1 measurable lesion, according to response evaluationcriteria in solid tumors (RECIST) v1.1 that has not been previously irradiated.Measurable lesions should not have been biopsied during screening, but if only 1non-irradiated measurable lesion exists, it may undergo a diagnostic biopsy and beacceptable as a target lesion, provided the baseline tumor assessment scans areperformed at least 14 days after the biopsy

Exclusion Criteria:

• Participant has received any prior systemic treatment at any time for locallyadvanced Stage III or metastatic Stage IV disease (adjuvant or neoadjuvant therapyfor Stage I or II disease is allowed, if administered more than 12 months prior tothe 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 beendefinitively treated with surgery or radiation and has a stable neurological statusfor at least 2 weeks prior to randomization is eligible provided they are offcorticosteroid treatment or receiving low-dose corticosteroid treatment less than orequal 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 excipientsused in formulation of amivantamab, lazertinib, or osimertinib, or anycontraindication to the use of osimertinib

• Participant has symptomatic brain metastases. A participant with asymptomatic orpreviously treated and stable brain metastases may participate in this study