DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing or -Mutated Non-Small Cell Lung Cancer

Inclusion Criteria:

- Age ≥20 years old in Japan, ≥18 years old in other countries

- Pathologically documented unresectable and/or metastatic non-squamous NSCLC

- Has relapsed from or is refractory to standard treatment or for which no standard
treatment is available

- For Cohort 1 only: HER2-overexpression (IHC 2+ or 3+) status must be assessed and
confirmed by Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory or
equivalent, from an archival tumor sample

- For Cohort 2 only: Documented any known activating HER2 mutation from an archival
tumor sample analyzed by CLIA laboratory or equivalent

- Presence of at least 1 measurable lesion assessed by the investigator based on
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

- Is willing and able to provide an adequate archival tumor sample

- Is willing to undergo a tissue biopsy, after the completion of the most recent
treatment regimen

- Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1

Exclusion Criteria:

- Was previously treated with HER2-targeted therapies, except for pan-HER class tyrosine
kinase inhibitors

- For Cohort 1 only: Has known HER2 mutation

- Has a medical history of myocardial infarction, symptomatic congestive heart failure
(CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia

- Has a QTc prolongation to > 450 millisecond (ms) in males and > 470 ms in females

- Has a medical history of clinically significant lung disease

- Is suspected to have certain other protocol-defined diseases based on imaging at
screening period

- Has history of any disease, metastatic condition, drug/medication use or other
condition that might, per protocol or in the opinion of the investigator, compromise:

1. safety or well-being of the participant or offspring

2. safety of study staff

3. analysis of results