A Study to Investigate the Efficacy and Safety of Trastuzumab Deruxtecan as the First Treatment Option for Unresectable, Locally Advanced/Metastatic Non-Small Cell Lung Cancer With HER2 Mutations

Study summary

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

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Key things to know

Main goalTreatment

This describes the study’s primary purpose.

What is being studiedTrastuzumab Deruxtecan and Cisplatin

Plus 3 other study approaches.

Who it may be forNon-small cell lung cancer (NSCLC) · HER2 · Early-stage or resectable

These are broad labels—not an eligibility decision.

Checked against the public recordLast updated Oct 21, 2026 · Source: ClinicalTrials.gov

Is enrollment open?Active Not Recruiting

The study is underway but is not accepting new participants.

What kind of study?Phase 3

Interventional

Where is it offered?130 U.S. locations

Locations may change over time.

Who runs it?AstraZeneca

Study sponsor

Study overview

What this study is about

Purpose: Treatment
Study type: Interventional
Phase: Phase 3
Sponsor: AstraZeneca
Interventions being studied: Drug: Trastuzumab Deruxtecan; Drug: Cisplatin; Drug: Carboplatin; Drug: Pembrolizumab; Drug: Pemetrexed

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How this study is categorized

These labels come from structured fields and exact terms in the public record.

Cancer type

Non-small cell lung cancer (NSCLC)→

Disease setting

Early-stage or resectable→Locally advanced→Metastatic or stage IV→

Biomarkers

HER2→

Treatment approach

Immunotherapy→Chemotherapy→

Public criteria

Who may be able to participate

The sponsor separates these requirements into two groups. You do not need to interpret them alone—use them to guide a conversation with the study team.

Requirements people may need to meetInclusion 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

Reasons someone may not be able to joinExclusion 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

Important: This is the sponsor’s public criteria, not a determination of eligibility. The study team must review your individual situation.

Study sites

U.S. locations

Research SiteAnchorage, Alaska
Research SiteLos Alamitos, California
Research SiteLos Angeles, California
Research SiteOrange, California
Research SiteSan Francisco, California
Research SiteSanta Monica, California
Research SiteSilver Spring, Maryland
Research SiteBoston, Massachusetts
Research SiteAnn Arbor, Michigan
Research SiteBasking Ridge, New Jersey
Research SiteMiddletown, New Jersey
Research SiteMontvale, New Jersey

Source and freshness
Processed from ClinicalTrials.gov. Last public update: Oct 21, 2026. Always confirm current availability with the study team.

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