Phase III Study of Datopotamab Deruxtecan Versus Docetaxel in Previously Treated TROP2-positive Advanced or Metastatic Non-squamous NSCLC Without Actionable Genomic Alterations

Official title

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)

Overview

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.

Interventions

• Drug Datopotamab deruxtecan (Dato-DXd)
  Dato-DXd administered intravenously (IV)
• Drug Docetaxel
  Docetaxel administered intravenously (IV)

Primary outcome measures

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

Secondary outcome measures (12)

• 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

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 50 centers

• Research Site — Chandler
• Research Site — Gilbert
• Research Site — Goodyear
• Research Site — Duarte
• Research Site — Irvine
• Research Site — La Jolla
• Research Site — Loma Linda
• Research Site — Los Angeles
• … and 42 more centers

China · 28 centers

• Research Site — Beijing
• Research Site — Beijing
• Research Site — Beijing
• … and 25 more centers

Germany · 16 centers

Center list to be confirmed — check the primary protocol.

Japan · 15 centers

Center list to be confirmed — check the primary protocol.

Hungary · 11 centers

Center list to be confirmed — check the primary protocol.

Spain · 7 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 7 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 7 centers

Center list to be confirmed — check the primary protocol.

Brazil · 6 centers

• Research Site — Porto Alegre
• Research Site — Porto Alegre
• Research Site — Salvador
• Research Site — São Paulo
• Research Site — São Paulo
• Research Site — São Paulo

Canada · 6 centers

• Research Site — Vancouver
• Research Site — Moncton
• Research Site — Halifax
• Research Site — Brampton
• Research Site — Hamilton
• Research Site — Toronto

Italy · 6 centers

Center list to be confirmed — check the primary protocol.

South Korea · 6 centers

Center list to be confirmed — check the primary protocol.

Australia · 5 centers

• Research Site — Gosford
• Research Site — Kogarah
• Research Site — South Brisbane
• Research Site — St Albans
• Research Site — Wollongong

Austria · 5 centers

• Research Site — Graz
• Research Site — Linz
• Research Site — Rankweil
• Research Site — Vienna
• Research Site — Vienna

Belgium · 5 centers

• Research Site — Hasselt
• Research Site — La Louvière
• Research Site — Libramont-Chevigny
• Research Site — Sint-Niklaas
• Research Site — Yvoir

France · 5 centers

Center list to be confirmed — check the primary protocol.

India · 5 centers

Center list to be confirmed — check the primary protocol.

Thailand · 5 centers

Center list to be confirmed — check the primary protocol.

Poland · 4 centers

Center list to be confirmed — check the primary protocol.

Vietnam · 4 centers

Center list to be confirmed — check the primary protocol.

Turkey (Türkiye) · 2 centers

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07291037 · D763QC00001 · 2024-520101-39-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗