The primary purpose of the study is to assess how well amivantamab in combination with lazertinib or in combination with chemotherapy works (antitumor activity) in participants with epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC; that is one of the major types of lung cancer).

Inclusion Criteria:

• Have histologically or cytologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC) that is not amenable to curative intent therapy
• Epidermal growth factor resistance-mutation (EGFRm) must be an Ex19del or Ex21 L858R substitution, as detected by food and drug administration (FDA)-approved or other validated test in a clinical laboratory improvement amendments (CLIA)-certified laboratory (sites in the US), or an accredited local laboratory (sites outside of the US) in accordance with site standard of care. In the European union (EU), the local test must be Conformité Européenne (CE)-marked or an in-house laboratory-developed test from health institutions in the EU in accordance with Article 5(5) of the in vitro diagnostic regulations (IVDR ) 2071/746, as amended
• Have at least 1 measurable lesion, according to RECIST version (v)1.1, that has not been previously irradiated
• Any toxicities from prior systemic anticancer therapy must have resolved to national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 5.0 grade 1 or baseline level (except for alopecia [any grade], grade <=2 peripheral neuropathy, or grade <=2 hypothyroidism stable on hormone replacement)
• Have an eastern cooperative oncology group (ECOG) performance status of 0 to 1

Exclusion Criteria:

• Medical history of active interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis. Participants with medical history of radiation pneumonitis, including radiation pneumonitis which required steroid treatment, should consult with the medical monitor and eligibility be assessed on a case-by-case basis
• Had major surgery excluding placement of vascular access or tumor biopsy or had significant traumatic injury within 4 weeks before the first dose of anticancer treatments or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study
• Participant has uncontrolled tumor-related pain (symptomatic lesions amenable to palliative radiotherapy should be treated prior to first dosing)
• Received an investigational treatment that has not been cleared (based on at least 5 half lives of any pharmaceutical treatment) before the planned first dose of study treatment or is currently enrolled in an investigational study
• Has a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment could likely interfere with any study endpoints of safety or the efficacy of the study treatment(s)

The data sharing policy of Johnson & Johnson Innovative Medicine is available at www.innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu.