Phase III Study of Datopotamab Deruxtecan Versus Docetaxel in Previously Treated TROP2-positive Advanced or Metastatic Non-squamous NSCLC Without Actionable Genomic Alterations

Study summary

TROPION-Lung17 will measure the efficacy and safety of datopotamab deruxtecan (Dato-DXd) compared with docetaxel in patients with trophoblast cell surface protein 2 (TROP2) positive advanced or metastatic lung cancer without actionable genomic alterations (AGA).

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Key things to know

Main goalTreatment

This describes the study’s primary purpose.

What is being studiedDatopotamab deruxtecan (Dato-DXd) and Docetaxel

The study team can explain what participation involves.

Who it may be forNon-small cell lung cancer (NSCLC) · Metastatic or stage IV

These are broad labels—not an eligibility decision.

Checked against the public recordLast updated Oct 13, 2026 · Source: ClinicalTrials.gov

Is enrollment open?Recruiting

The study is currently accepting participants.

What kind of study?Phase 3

Interventional

Where is it offered?206 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: Datopotamab deruxtecan (Dato-DXd); Drug: Docetaxel

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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

Metastatic or stage IV→

Treatment approach

Chemotherapy→

Study topics

After prior treatment→

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

\- Pathologically documented Stage IIIB, IIIC, or Stage IV non-squamous non-small cell lung cancer (NSCLC) without actionable genomic alterations (AGA) at the time of randomisation and meets the criteria for NSCLC:
Participants must have documented negative test results for EGFR (eg, exon 19 deletion or exon 21 L858R, exon 21 L861Q, exon 18 G719X, or exon 20 S768I mutation), ALK, and ROS1 genomic alterations. Note: If test results for EGFR, ALK, and ROS1 are not available, participants are required to undergo prospective testing performed centrally for these genomic alterations in a Sponsor-designated central laboratory.
Has no known tumour genomic alterations in NTRK, BRAF V600, RET, MET exon 14 skipping, KRAS G12C, or HER2. Additionally, participants must not have known tumour genomic alteration of any other actionable driver oncogenes for which there are locally approved targeted first-line therapies. Note: Participants whose tumours harbour BRAF (exception V600) or KRAS (exception G12C) mutations are eligible for the study.
Prospectively assessed TROP2 NMR positive based on results from an appropriately validated investigational TROP2 RxDx device in a Sponsor- designated, regulatory compliant central laboratory.
Documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC.
Participants must have received platinum based chemotherapy (PBC) in combination with anti-programmed death-protein 1 (anti-PD-1)/anti-programmed death-ligand 1 (anti-PD-L1) monoclonal antibody (mAb) as the only prior line of therapy or received PBC and anti-PD-1/anti-PD-L1 monoclonal antibody (in either order) sequentially as the only 2 prior lines of therapy.
Provision of acceptable formalin fixed and paraffin embedded (FFPE) tumour sample for assessment of TROP2.
At least one lesion not previously irradiated that qualifies as a Response Evaluation Criteria in Solid Tumours, Version 1.1 (RECIST 1.1) target lesion (TL) at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for accurate repeated measurements.
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
Adequate bone marrow reserve and organ function within 7 days before randomisation.

Reasons someone may not be able to joinExclusion criteria

Squamous, mixed NSCLC, or small cell lung cancer (SCLC) histology.
NSCLC disease that is eligible for definitive local therapy alone.
History of another primary malignancy other than NSCLC, except for malignancy treated with curative intent with no known active disease within 3 years before randomisation and of low potential risk for recurrence.
Spinal cord compression or brain metastases, unless asymptomatic, stable, and not requiring treatment with corticosteroids or anticonvulsants for at least 7 days prior to randomisation.
Clinically significant corneal disease.
Has active or uncontrolled hepatitis B or C virus infection.
Known human immunodeficiency virus (HIV) infection that is not well controlled.
Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals.
History of ILD/pneumonitis, including radiation pneumonitis (apart from radiation pneumonitis that did not require steroids), or drug-induced ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening. Examples of suspected ILD/pneumonitis by imaging include the presence of lung parenchymal fibrosis, such as combined pulmonary fibrosis and emphysema (CPFE), and any radiographic features consistent with interstitial lung abnormalities, including but not limited to, extensive ground glass opacities, reticular opacities, traction bronchiectasis, and honeycombing.
Has severe pulmonary function compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the study enrolment, severe asthma, severe COPD, restrictive lung disease, symptomatic pleural effusion, etc).

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 SiteChandler, Arizona
Research SiteGilbert, Arizona
Research SiteGoodyear, Arizona
Research SiteDuarte, California
Research SiteIrvine, California
Research SiteLa Jolla, California
Research SiteLoma Linda, California
Research SiteLos Angeles, California
Research SiteSan Diego, California
Research SiteGrand Junction, Colorado
Research SiteWheat Ridge, Colorado
Research SiteNewark, Delaware

Source and freshness
Processed from ClinicalTrials.gov. Last public update: Oct 13, 2026. Always confirm current availability with the study team.

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