The purpose of this study is to evaluate izalontamab brengitecan (iza-bren) combined with osimertinib in participants with previously untreated, locally advanced or metastatic EGFR-mutant NSCLC, compared to osimertinib alone or osimertinib combined with platinum-based chemotherapy
Participants must have histologically or cytologically confirmed non-squamous NSCLC, newly diagnosed locally advanced (Stage IIIB/IIIC), metastatic (Stage IVA/IVB), or recurrent disease not amenable to curative surgery or definitive radiotherapy and requiring systemic treatment
Participants must have documented EGFR-TKI-sensitizing mutation (exon 19 deletion or exon 21 L858R substitution)
Participants must have measurable extracranial disease per RECIST v1.1 as assessed by the investigator
Participants must have ECOG Performance Status 0-1
Participants must not have unstable, symptomatic, or uncontrolled CNS metastases, including brain, leptomeningeal disease, and/or spinal cord compression
Participants must not have history of ILD/pneumonitis requiring treatment with steroids (≥ Grade 2), or current or suspected ILD/pneumonitis
Participants must not have clinically significant cardiac disease
Other protocol-defined inclusion/exclusion criteria apply.