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Investigating Dato-DXd with or without Osimertinib for advanced lung cancer

A Phase III, Open-label, Sponsor-blind, Randomized Study of Dato-DXd With or Without Osimertinib Versus Platinum-based Doublet Chemotherapy for Participants With EGFR-mutated Locally Advanced or Metastatic Non-small Cell Lung Cancer Whose Disease Has Progressed on Prior Osimertinib Treatment (TROPION-Lung15)

PHASE3 · AstraZeneca · NCT06417814

This study is testing a new treatment called Dato-DXd, with and without another drug called osimertinib, to see if it helps people with advanced lung cancer who have already tried other therapies.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment744 (estimated)
Ages18 Years to 130 Years
SexAll
SponsorAstraZeneca (industry)
Drugs / interventionsosimertinib, chemotherapy, immunotherapy, radiation
Locations302 sites (Fayetteville, Arkansas and 301 other locations)
Trial IDNCT06417814 on ClinicalTrials.gov

What this trial studies

This Phase III, open-label, multicenter study evaluates the efficacy and safety of Dato-DXd, both in combination with osimertinib and as a monotherapy, compared to standard platinum-based doublet chemotherapy in patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). Participants will be randomized into three groups to assess progression-free survival (PFS) and safety outcomes. The study aims to provide insights into treatment options for patients whose disease has progressed after prior osimertinib therapy.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed non-squamous NSCLC who have documented EGFR mutations and have experienced disease progression on prior osimertinib treatment.

Not a fit: Patients with squamous cell carcinoma or those who have not received prior osimertinib may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could offer a new effective treatment option for patients with advanced EGFR-mutated NSCLC.

How similar studies have performed: Other studies have shown promising results with similar targeted therapies in EGFR-mutated lung cancer, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion 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.

Exclusion 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.

Where this trial is running

Fayetteville, Arkansas and 301 other locations

+252 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Metastatic Non-small Cell Lung Cancer, Epidermal growth factor receptor gene mutation, Standard of Care, Locally, advanced carcinoma, Metastatic carcinoma, Non-small cell lung cancer, Dato-dxd, Datopotamab deruxtecan

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.