Recruiting
Phase 3

Dato-DXd vs. Docetaxel

Sponsor:

AstraZeneca

Code:

NCT07291037

Conditions

Non-small Cell Lung Cancer (NSCLC)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Datopotamab deruxtecan (Dato-DXd)

Docetaxel

Study Details

Brief 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).

Conditions

Non-small Cell Lung Cancer (NSCLC)

Study ID

NCT07291037

Start date

Oct 31, 2025

Status verified date

Aug, 2026

Completion date

Jan 29, 2029

Anticipated

Primary completion date

Jan 29, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 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.

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 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).

Study Design

Enrollment

400 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A: Datopotamab deruxtecan (Dato-DXd) monotherapy

Participants in the Dato-DXd monotherapy group will receive Dato-DXd as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

active comparator: Arm B: Docetaxel monotherapy

Participants in the docetaxel monotherapy group will receive docetaxel as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

Interventions

Datopotamab deruxtecan (Dato-DXd)

Dato-DXd administered intravenously (IV)

Docetaxel

Docetaxel administered intravenously (IV)

Primary outcome measure

  • Progression-free survival (PFS) [ Time Frame: Approximately 2.5 years ]
  • Overall survival (OS) [ Time Frame: Approximately 3.5 years ]

Central Contacts and Locations

Central contacts

AstraZeneca Clinical Study Information Center

1-877-240-9479information.center@astrazeneca.com

Locations

Research Site

Recruiting

Chandler, Arizona, United States, 85224

Research Site

Recruiting

Gilbert, Arizona, United States, 85234

Research Site

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Goodyear, Arizona, United States, 85338

Research Site

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Duarte, California, United States, 91010

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Irvine, California, United States, 92618

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La Jolla, California, United States, 92093

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Loma Linda, California, United States, 92350

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Los Angeles, California, United States, 90095

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San Diego, California, United States, 92123

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Grand Junction, Colorado, United States, 81501

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Wheat Ridge, Colorado, United States, 80033

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Newark, Delaware, United States, 19713

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Fort Myers, Florida, United States, 33901

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Jacksonville, Florida, United States, 32224

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St. Petersburg, Florida, United States, 33709

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Tampa, Florida, United States, 33612

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West Palm Beach, Florida, United States, 33401

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Marietta, Georgia, United States, 30060

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Newnan, Georgia, United States, 30265

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Chicago, Illinois, United States, 60612

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Chicago, Illinois, United States, 60637

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Niles, Illinois, United States, 60714

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Zion, Illinois, United States, 60099

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Louisville, Kentucky, United States, 40207

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South Portland, Maine, United States, 04106

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Baltimore, Maryland, United States, 21201

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Brandywine, Maryland, United States, 20613

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Boston, Massachusetts, United States, 02215

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Detroit, Michigan, United States, 48202

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Rochester, Minnesota, United States, 55905

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Bridgeton, Missouri, United States, 63044

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Lincoln, Nebraska, United States, 68516

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Albuquerque, New Mexico, United States, 87109

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East Syracuse, New York, United States, 13057

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Hershey, Pennsylvania, United States, 17033

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Lancaster, Pennsylvania, United States, 17601

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Greenville, South Carolina, United States, 29607

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Memphis, Tennessee, United States, 38120

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Austin, Texas, United States, 78745

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Denton, Texas, United States, 76201

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Plano, Texas, United States, 75075

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Charlottesville, Virginia, United States, 22908

Research Site

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Fairfax, Virginia, United States, 22031

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Williamsburg, Virginia, United States, 23188

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Tacoma, Washington, United States, 98405

Research Site

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Morgantown, West Virginia, United States, 26506

Research Site

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Eau Claire, Wisconsin, United States, 54703

Research Site

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Vancouver, British Columbia, Canada, VSZ 4E6

Research Site

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Moncton, New Brunswick, Canada, E1C 6Z8

Research Site

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Halifax, Nova Scotia, Canada, B3H 2Y9

Research Site

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Brampton, Ontario, Canada, L6R 3J7

Research Site

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Hamilton, Ontario, Canada, L8V 1C3

Research Site

Recruiting

Toronto, Ontario, Canada, M5G 1X6

More Information

Sponsor

AstraZeneca

Last update posted

Sep 4, 2026

Last verified

Aug, 2026

Keywords

  • TROPION-Lung17
  • Non-small cell lung cancer (NSCLC)
  • Advanced non-squamous NSCLC
  • Metastatic non-squamous NSCLC
  • Datopotamab deruxtecan (Dato-DXd; DS-1062a)
  • Docetaxel
  • Trophoblast cell surface protein 2 (TROP2)
  • Normalised membrane ratio (NMR)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by AstraZeneca on 2026-09-04.