Home › Trials › NCT07291037

Datopotamab deruxtecan versus docetaxel for previously treated TROP2-positive advanced non-squamous NSCLC

A Phase III, Randomised, Open-Label, Multicentre Study of Datopotamab Deruxtecan or Docetaxel in Previously Treated TROP2-positive Advanced or Metastatic Non-squamous Non-Small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung17)

Phase 3 Interventional AstraZeneca · NCT07291037

This trial tests whether datopotamab deruxtecan works better than docetaxel for people with TROP2-positive advanced or metastatic non-squamous NSCLC who have already received prior therapy and do not have actionable genomic alterations.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment400 (estimated)
Ages18 Years and up
SexAll
SponsorAstraZeneca Industry-sponsored
Drugs / interventionschemotherapy, radiation, datopotamab
Locations204 sites (Chandler, Arizona and 203 other locations)
Trial IDNCT07291037 on ClinicalTrials.gov

What this trial studies

This is a randomized, open-label Phase III trial that assigns participants to receive either datopotamab deruxtecan (Dato-DXd) or docetaxel. Eligible participants have previously treated advanced or metastatic non-squamous NSCLC, are TROP2-positive by a normalized membrane ratio (NMR) test, and lack actionable genomic driver alterations like EGFR, ALK, or ROS1. The trial compares efficacy and safety between the two arms and also evaluates the performance of an investigational in vitro diagnostic (IVD) device for TROP2 testing. Multiple visits to participating research sites in Arizona are required for treatment and follow-up.

Who should consider this trial

Good fit: Ideal candidates are adults with previously treated stage IIIB–IV non-squamous NSCLC who are TROP2 NMR-positive and have no actionable genomic alterations (e.g., EGFR, ALK, ROS1, BRAF, RET, MET exon 14, KRAS G12C, NTRK, HER2).

Not a fit: Patients with actionable driver mutations, squamous-cell histology, or confirmed TROP2-negative tumors are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, this could provide a more effective and/or better tolerated treatment option than docetaxel for TROP2-positive, previously treated non-squamous NSCLC.

How similar studies have performed: Earlier-phase trials of datopotamab deruxtecan have shown promising response rates in TROP2-positive NSCLC, but phase III confirmation is still needed.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion 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 epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) genomic alterations.
  * Has no known tumour genomic alterations in neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), rearranged during transfection (RET), mesenchymal-epithelial transition (MET) exon 14 skipping, Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C, human epidermal growth factor receptor 2 (HER2) or any other actionable driver oncogenes for which there are locally approved and available targeted first-line therapies.
  * Prospectively assessed trophoblast cell surface protein 2 (TROP2) normalised membrane ratio (NMR) positive.
* 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.

Exclusion 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 non-infectious interstitial lung disease (ILD)/pneumonitis including radiation pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
* Severe pulmonary function compromise per Investigator discretion.

Where this trial is running

Chandler, Arizona and 203 other locations

+154 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 → Find more trials like this →
Conditions Non-small Cell Lung CancerTROPION-Lung17Non-small cell lung cancerAdvanced non-squamous NSCLCMetastatic non-squamous NSCLCDatopotamab deruxtecan (Dato-DXdDS-1062a)Docetaxel
Last reviewed 2026-06-10 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.