Phase III Study of Datopotamab Deruxtecan Versus Docetaxel in Previously Treated TROP2-positive Advanced or Metastatic Non-squamous NSCLC Without Actionable Genomic Alterations
Purpose
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).
Condition
- Non-small Cell Lung Cancer (NSCLC)
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy 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 Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Arm A: Datopotamab deruxtecan monotherapy Arm B: Docetaxel monotherapy
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
- Masking Description
- TROPION-Lung17 is an open-label study; however, the study will be conducted as 'Sponsor-blind'.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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. |
|
Recruiting Locations
Research Site
Chandler, Arizona 85224
Chandler, Arizona 85224
Research Site
Gilbert, Arizona 85234
Gilbert, Arizona 85234
Research Site
Goodyear, Arizona 85338
Goodyear, Arizona 85338
Research Site
Duarte, California 91010
Duarte, California 91010
Research Site
Irvine, California 92618
Irvine, California 92618
Research Site
La Jolla, California 92093
La Jolla, California 92093
Research Site
Loma Linda, California 92350
Loma Linda, California 92350
Research Site
San Diego, California 92123
San Diego, California 92123
Research Site
Grand Junction, Colorado 81501
Grand Junction, Colorado 81501
Research Site
Wheat Ridge, Colorado 80033
Wheat Ridge, Colorado 80033
Research Site
Newark, Delaware 19713
Newark, Delaware 19713
Research Site
Fort Myers, Florida 33901
Fort Myers, Florida 33901
Research Site
Jacksonville, Florida 32224
Jacksonville, Florida 32224
Research Site
St. Petersburg, Florida 33709
St. Petersburg, Florida 33709
Research Site
Tampa, Florida 33612
Tampa, Florida 33612
Research Site
West Palm Beach, Florida 33401
West Palm Beach, Florida 33401
Research Site
Marietta, Georgia 30060
Marietta, Georgia 30060
Research Site
Newnan, Georgia 30265
Newnan, Georgia 30265
Research Site
Chicago, Illinois 60612
Chicago, Illinois 60612
Research Site
Chicago, Illinois 60637
Chicago, Illinois 60637
Research Site
Niles, Illinois 60714
Niles, Illinois 60714
Research Site
Zion, Illinois 60099
Zion, Illinois 60099
Research Site
Louisville, Kentucky 40207
Louisville, Kentucky 40207
Research Site
South Portland, Maine 04106
South Portland, Maine 04106
Research Site
Baltimore, Maryland 21201
Baltimore, Maryland 21201
Research Site
Brandywine, Maryland 20613
Brandywine, Maryland 20613
Research Site
Boston, Massachusetts 02215
Boston, Massachusetts 02215
Research Site
Detroit, Michigan 48202
Detroit, Michigan 48202
Research Site
Rochester, Minnesota 55905
Rochester, Minnesota 55905
Research Site
Bridgeton, Missouri 63044
Bridgeton, Missouri 63044
Research Site
Lincoln, Nebraska 68516
Lincoln, Nebraska 68516
Research Site
Albuquerque, New Mexico 87109
Albuquerque, New Mexico 87109
Research Site
East Syracuse, New York 13057
East Syracuse, New York 13057
Research Site
Hershey, Pennsylvania 17033
Hershey, Pennsylvania 17033
Research Site
Lancaster, Pennsylvania 17601
Lancaster, Pennsylvania 17601
Research Site
Greenville, South Carolina 29607
Greenville, South Carolina 29607
Research Site
Memphis, Tennessee 38120
Memphis, Tennessee 38120
Research Site
Austin, Texas 78745
Austin, Texas 78745
Research Site
Denton, Texas 76201
Denton, Texas 76201
Research Site
Plano, Texas 75075
Plano, Texas 75075
Research Site
Charlottesville, Virginia 22908
Charlottesville, Virginia 22908
Research Site
Fairfax, Virginia 22031
Fairfax, Virginia 22031
Research Site
Williamsburg, Virginia 23188
Williamsburg, Virginia 23188
Research Site
Tacoma, Washington 98405
Tacoma, Washington 98405
Research Site
Morgantown, West Virginia 26506
Morgantown, West Virginia 26506
Research Site
Eau Claire, Wisconsin 54703
Eau Claire, Wisconsin 54703
More Details
- Status
- Recruiting
- Sponsor
- AstraZeneca
Study Contact
AstraZeneca Clinical Study Information Center1-877-240-9479
information.center@astrazeneca.com
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.