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RecruitingInterventionalPhase 3

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)

NCT ID: NCT07291037Sponsor: AstraZenecaLast updated: 2026-06-01

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).

Detailed description

TROPION-Lung17 is a phase III, 2-arm, randomised, open-label, multicentre study, assessing the efficacy and safety of Dato-DXd compared with docetaxel in participants with previously treated trophoblast cell surface protein 2 (TROP2) normalised membrane ratio (NMR) positive advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) without actionable genomic alterations (AGA), and to assess the clinical performance of the investigational in vitro diagnostic (IVD) device.

Arms & interventions

  • DrugDatopotamab deruxtecan (Dato-DXd)

    Dato-DXd administered intravenously (IV)

  • DrugDocetaxel

    Docetaxel administered intravenously (IV)

Outcome measures

Primary

  • Progression-free survival (PFS)

    PFS is defined as the time from randomization until radiological progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR), or death due to any cause.

    Time frame: Approximately 2.5 years

  • Overall survival (OS)

    OS is defined as the time from randomization until the date of death due to any cause.

    Time frame: Approximately 3.5 years

Secondary

  • Objective response rate (ORR)

    Time frame: Approximately 2.5 years

  • Duration of response (DoR)

    Time frame: Approximately 2.5 years

  • Time to second progression or death (PFS2)

    Time frame: Approximately 2.5 years

  • Exposure-efficacy relationship

    Time frame: Approximately 2.5 years

  • Exposure-safety relationship

    Time frame: Approximately 2.5 years

  • Covariates effect on exposure

    Time frame: Approximately 2.5 years

  • Immunogenicity of datopotamab deruxtecan (Dato-DXd)

    Time frame: Approximately 2.5 years

  • Participant-reported lung cancer symptoms of non-small cell lung cancer (NSCLC)

    Time frame: Approximately 2.5 years

  • Participant-reported physical functioning

    Time frame: Approximately 2.5 years

  • Participant-reported global health status (GHS)/quality of life (QoL)

    Time frame: Approximately 2.5 years

  • Correlation of TROP2 expression at various cut offs with clinical response

    Time frame: Approximately 2.5 years

  • Diagnostic development and biomarker assay concordance analysis

    Time frame: Approximately 2.5 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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.

Study locations (50)

Research Site

Chandler, Arizona, 85224

Recruiting

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Gilbert, Arizona, 85234

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Goodyear, Arizona, 85338

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Duarte, California, 91010

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Irvine, California, 92618

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La Jolla, California, 92093

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Loma Linda, California, 92350

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Los Angeles, California, 90095

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San Diego, California, 92123

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Grand Junction, Colorado, 81501

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Wheat Ridge, Colorado, 80033

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Newark, Delaware, 19713

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Washington D.C., District of Columbia, 20037

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Fort Myers, Florida, 33901

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Jacksonville, Florida, 32224

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St. Petersburg, Florida, 33709

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Tampa, Florida, 33612

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West Palm Beach, Florida, 33401

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Marietta, Georgia, 30060

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Newnan, Georgia, 30265

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Chicago, Illinois, 60612

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Chicago, Illinois, 60637

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Niles, Illinois, 60714

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Zion, Illinois, 60099

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Louisville, Kentucky, 40207

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South Portland, Maine, 04106

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Baltimore, Maryland, 21201

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Brandywine, Maryland, 20613

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Boston, Massachusetts, 02215

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Detroit, Michigan, 48202

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Rochester, Minnesota, 55905

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Bridgeton, Missouri, 63044

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Columbia, Missouri, 65212

Withdrawn

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Lincoln, Nebraska, 68516

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Albuquerque, New Mexico, 87109

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East Syracuse, New York, 13057

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Portland, Oregon, 97239

Withdrawn

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Hershey, Pennsylvania, 17033

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Philadelphia, Pennsylvania, 19104

Not Yet Recruiting

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Greenville, South Carolina, 29607

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Memphis, Tennessee, 38120

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Austin, Texas, 78745

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Denton, Texas, 76201

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Plano, Texas, 75075

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Charlottesville, Virginia, 22908

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Fairfax, Virginia, 22031

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Williamsburg, Virginia, 23188

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Tacoma, Washington, 98405

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Morgantown, West Virginia, 26506

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Eau Claire, Wisconsin, 54703

Recruiting