Cancer Clinical Research Unit

Inclusion Criteria: - 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 Exclusion Criteria: - Tumors with targetable alterations to EGFR (or other targetable mutations including but not limited to ALK, if routinely tested as a targetable alteration with approved available therapy) - Any untreated brain metastases, including asymptomatic or clinically inactive brain metastases - Active autoimmune or inflammatory disorders - Medical history of myocardial infarction within 6 months prior to randomization - History of non-infectious pneumonitis/ILD, current or suspected ILD - Lung-specific intercurrent clinical significant severe illness - Contraindication to platinum-based doublet chemotherapy or pembrolizumab