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

A Phase 2, Multicenter, Open-Label, 2-Cohort Study of Trastuzumab Deruxtecan (DS-8201a), an Anti-HER2 Antibody Drug Conjugate (ADC), for HER2-Over-Expressing or -Mutated, Unresectable and/or Metastatic Non Small Cell Lung Cancer (NSCLC) (DESTINY-Lung01)

The primary objective of this trial is to evaluate the efficacy of trastuzumab deruxtecan in HER2-overexpressing and/or HER2-mutated advanced NSCLC participants.

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 and Cohort 1a: 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 tissue sample
• For Cohort 2 only: Participant has any known documented activating HER2 mutation from an archival tumor tissue sample analyzed by CLIA laboratory or equivalent. Note: HER2 mutation documented only from a liquid biopsy sample cannot be used for enrollment.
• Presence of at least 1 measurable lesion assessed by the investigator and based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Is willing and able to provide an adequate archival tumor tissue 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:

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

• For Cohort 1 and Cohort 1a: 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 history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, or current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out due to imaging at screening

• Has a QT interval corrected by Fridericia's formula (QTcF) 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