• Participants at least 18 years of age

• Locally advanced and unresectable NSCLC, not amenable to curative therapy, or metastatic disease

• Histologically documented non-squamous NSCLC with HER2 mutation in exons 19 or 20 by tissue NGS or ctDNA

• Treatment-naïve for palliative intent systemic therapy for locally advanced or metastatic disease

• Left ventricular ejection fraction (LVEF) ≥ 50%

• Measurable disease assessed by Investigator based on RECIST 1.1

• Protocol-defined adequate organ function including cardiac, renal, hepatic function

• ECOG 0-1

• Having tumour tissue available for central testing