Clinical Trial 23805

• Overview

  Study 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)

  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).

  Objective:

  Primary objectives *To assess the superiority of Dato-DXd vs docetaxel by assessment of PFS by BICR in participants with TROP2 QCS-NMR positive non-squamous NSCLC without AGA *To assess the superiority of Dato-DXd vs docetaxel by assessment of OS in participants with TROP2 QCS-NMR positive non-squamous NSCLC without AGA Secondary objectives *To assess the superiority of Dato-DXd vs docetaxel by assessment of ORR in participants with TROP2 QCS-NMR positive non-squamous NSCLC without AGA *To assess the superiority of Dato-DXd vs docetaxel by assessment of DoR in participants with TROP2 QCS-NMR positive non-squamous NSCLC without AGA *To assess the superiority of Dato-DXd vs docetaxel in terms of PFS2 in participants with TROP2 QCS-NMR positive non-squamous NSCLC without AGA *To evaluate exposure response relationship for efficacy and safety endpoints *To investigate the immunogenicity of Dato-DXd *To assess participant-reported lung cancer symptoms of NSCLC in participants treated with Dato-DXd relative to docetaxel *To assess participant-reported physical functioning in participants treated with Dato-DXd relative to docetaxel *To assess participant-reported GHS/QoL in participants treated with Dato-DXd relative to docetaxel *To assess TROP2 diagnostic test performance and relationship with other tumour-derived biomarkers or diagnostics tests, and support diagnostic test development

• Treatments

  Therapies:

  Chemotherapy (NOS); TROP2-targeted Antibody drug conjugate

  Medications:

  Datopotamab Deruxtecan (); Taxotere (docetaxel); docetaxel ()

• Inclusion Criteria

  Key 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.
  • Additional Criteria May Apply.

• Exclusion Criteria

  Key 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.
  • Additional Criteria May Apply.

If you are interested in learning more about clinical trials, our clinical trial navigators can discuss your options and recommend opportunities that may be suitable for you. Call 813-745-6100 or 1-800-679-0775 (toll-free) or submit a clinical trials inquiry form.