Phase III Study of Datopotamab Deruxtecan Versus Docetaxel in Previously Treated TROP2-positive Advanced or Metastatic Non-squamous NSCLC Without Actionable Genomic Alterations
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).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
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 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).
Primary outcome measure(s)
Progression-free survival (PFS) — Approximately 2.5 years 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.
Overall survival (OS) — Approximately 3.5 years OS is defined as the time from randomization until the date of death due to any cause.
Trial sites (206)
Facility
City
Region
Status
Research Site
Chandler
Arizona
Recruiting
Research Site
Gilbert
Arizona
Recruiting
Research Site
Goodyear
Arizona
Recruiting
Research Site
Duarte
California
Recruiting
Research Site
Irvine
California
Recruiting
Research Site
La Jolla
California
Recruiting
Research Site
Loma Linda
California
Recruiting
Research Site
Los Angeles
California
Recruiting
Research Site
San Diego
California
Recruiting
Research Site
Grand Junction
Colorado
Recruiting
Research Site
Wheat Ridge
Colorado
Recruiting
Research Site
Newark
Delaware
Recruiting
Research Site
Washington D.C.
District of Columbia
Withdrawn
Research Site
Fort Myers
Florida
Recruiting
Research Site
Jacksonville
Florida
Recruiting
Research Site
St. Petersburg
Florida
Recruiting
Research Site
Tampa
Florida
Recruiting
Research Site
West Palm Beach
Florida
Recruiting
Research Site
Marietta
Georgia
Recruiting
Research Site
Newnan
Georgia
Recruiting
Research Site
Chicago
Illinois
Recruiting
Research Site
Chicago
Illinois
Recruiting
Research Site
Hinsdale
Illinois
Not Yet Recruiting
Research Site
Niles
Illinois
Recruiting
Research Site
Zion
Illinois
Recruiting
Research Site
Louisville
Kentucky
Recruiting
Research Site
South Portland
Maine
Recruiting
Research Site
Baltimore
Maryland
Recruiting
Research Site
Brandywine
Maryland
Recruiting
Research Site
Boston
Massachusetts
Recruiting
Research Site
Detroit
Michigan
Recruiting
Research Site
Rochester
Minnesota
Recruiting
Research Site
Bridgeton
Missouri
Recruiting
Research Site
Columbia
Missouri
Withdrawn
Research Site
Lincoln
Nebraska
Recruiting
Research Site
Albuquerque
New Mexico
Recruiting
Research Site
East Syracuse
New York
Recruiting
Research Site
Portland
Oregon
Withdrawn
Research Site
Hershey
Pennsylvania
Recruiting
Research Site
Lancaster
Pennsylvania
Recruiting
+ 166 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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