An Open-label, Randomized, Multicenter, Phase 3 Study to Assess the Efficacy and Safety of Trastuzumab Deruxtecan as First-line Treatment of Unresectable, Locally Advanced, or Metastatic NSCLC Harboring HER2 Exon 19 or 20 Mutations (DESTINY-Lung04)

Protocol # :
Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Disease Sites
Principal Investigator
Rotow, Julia, Kathleen
Site Research Nurses
Becker, Simone
Janell, Samantha
Kelley, Elaine
Lam, Ethan
MacLeod, Taylor, H.
Mcnally, Megan
Souza, Joseph
Sullivan, Molly, O'Brien
Thistle, Katrina, M.

Trial Description

DESTINY-Lung04 will investigate the efficacy and safety of Trastuzumab Deruxtecan (T-DXd)
versus Standard of Care (SoC) as first-line treatment of Non-Small Cell Lung Cancer (NSCLC)
with HER2 Exon 19 or 20 mutations

Eligibility Requirements

Inclusion Criteria:

- Participants at least 18 years of age

- Locally advanced 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 clinically active brain metastases; previously treated brain metastases allowed

- 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