for people ages 18-123 (full criteria)
at San Francisco, California and other locations
study started
completion around



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

Official Title

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)


Eligible participants will be those diagnosed with unresectable, locally advanced or metastatic histologically documented non-squamous NSCLC with HER2 exons 19 or 20 mutations and who are treatment-naïve for palliative intent systemic therapy for locally advanced or metastatic disease.

The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan as first-line treatment of Non-Small Cell Lung Cancer (NSCLC) as compared with Standard of Care treatment (Investigator's choice of cisplatin or carboplatin + pembrolizumab + pemetrexed). This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse or simply to live longer, compared to patients receiving standard of care treatment. This study is also looking to see how the treatment and the cancer affects patients' quality of life.


Locally Advanced or Metastatic Non-Small Cell Lung Cancer, DS-8201a, HER2 exon 19 or 20 mutations, ERBB2 gene (coding for the HER2 protein), T-DXd, Trastuzumab Deruxtecan, Locally advanced and unresectable non-squamous NSCLC, Metastatic non-squamous NSCLC, Non-small cell lung cancer, Lung Neoplasms, Non-Small-Cell Lung Carcinoma, Carboplatin, Pembrolizumab, Trastuzumab, Pemetrexed, Cisplatin


You can join if…

Open to people ages 18-123

  • 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

You CAN'T join if...

  • 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


  • Research Site currently not accepting new patients, but might later
    San Francisco California 94143 United States
  • Research Site accepting new patients
    Santa Rosa California 95403 United States
  • Research Site accepting new patients
    Los Angeles California 90048 United States
  • Research Site accepting new patients
    Santa Monica California 90404 United States


accepting new patients at some sites,
but this study is not currently recruiting here
Start Date
Completion Date
Phase 3 research study
Study Type
Expecting 450 study participants
Last Updated