A Study to Investigate the Efficacy and Safety of Dato-DXd With or Without Osimertinib Compared With Platinum Based Doublet Chemotherapy in Participants With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Study summary

This study will assess the effect of Dato-DXd in combination with osimertinib or Dato-DXd monotherapy versus platinum-based doublet chemotherapy in terms of progression-free survival (PFS).

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Key things to know

Main goalTreatment

This describes the study’s primary purpose.

What is being studiedDato-DXd and Osimertinib

Plus 3 other study approaches.

Who it may be forNon-small cell lung cancer (NSCLC) · EGFR · Locally advanced

These are broad labels—not an eligibility decision.

Checked against the public recordLast updated Oct 15, 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?211 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: Dato-DXd; Drug: Osimertinib; Drug: Pemetrexed; Drug: Carboplatin; Drug: Cisplatin

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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

Locally advanced→Metastatic or stage IV→

Biomarkers

EGFR→

Treatment approach

Targeted therapy→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

\- Histologically or cytologically confirmed non-squamous NSCLC.
\- Must have evidence of documented pre-existing EGFRm information (EGFRm known to be associated with (epidermal growth factor receptor \[EGFR\] tyrosine kinase inhibitor \[TKis\] sensitivity \[Ex19del, L858R, G719X, S768I, or L861Q\], either alone or in combination with other EGFR mutations, which may include T790M).
\- Documented extra-cranial radiologic progression on prior osimertinib monotherapy (as most recent line of treatment) in the adjuvant, locally advanced, or metastatic setting.
\- Less than or equal to (\<=2) prior lines of EGFR TKIs (osimertinib is the only permitted prior third generation EGFR TKI).
\- At least one lesion, not previously irradiated, that qualifies as a RECIST v1.1 TL at baseline and can be accurately measured at baseline.
\- World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
\- Adequate bone marrow reserve and organ function within 7 days before randomization.

Reasons someone may not be able to joinExclusion criteria

\- Use of chemotherapy, vascular endothelial growth factor inhibitor, immunotherapy or any anti-cancer therapy in the metastatic setting. Platinum-based chemotherapy in non-metastatic setting within 12 months prior to randomization.
\- History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 2 years before the first dose of study intervention.
\- Any evidence of severe or uncontrolled systemic diseases, including, but not limited to active bleeding diseases, active infection, active ILD/pneumonitis, cardiac disease.
\- Has significant third-space fluid retention (example \[eg.\], ascites or pleural effusion) as judged by the investigator and is not amenable for required repeated drainage.
\- History of non-infectious ILD/pneumonitis including radiation pneumonitis that required steroids or drug-induced ILD, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
\- Has severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.
-Unstable spinal cord compression and/or unstable brain metastases.
\- Participants with symptomatic brain metastases (including leptomeningeal involvement).
\- Clinically significant corneal disease.
\- Uncontrolled infection requiring systemic antibiotics, antivirals, or antifungals, suspected infections or inability to rule out infections. Use of systemic antibiotics within 14 days of randomization.
\- Has known human immunodeficiency virus (HIV) infection that is not well controlled.

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 SiteFayetteville, Arkansas
Research SiteFountain Valley, California
Research SiteSan Diego, California
Research SiteJacksonville, Florida
Research SiteKansas City, Missouri
Research SiteNew York, New York
Research SiteMaumee, Ohio
Research SitePittsburgh, Pennsylvania
Research SiteNashville, Tennessee
Research SiteFitzroy
Research SiteHeidelberg
Research SiteKogarah

Source and freshness
Processed from ClinicalTrials.gov. Last public update: Oct 15, 2026. Always confirm current availability with the study team.

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