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

Официальное название

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)

Обзор

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).

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (12)

• Objective response rate (ORR) [Срок оценки: Approximately 2.5 years]
• Duration of response (DoR) [Срок оценки: Approximately 2.5 years]
• Time to second progression or death (PFS2) [Срок оценки: Approximately 2.5 years]
• Exposure-efficacy relationship [Срок оценки: Approximately 2.5 years]
• Exposure-safety relationship [Срок оценки: Approximately 2.5 years]
• Covariates effect on exposure [Срок оценки: Approximately 2.5 years]
• Immunogenicity of datopotamab deruxtecan (Dato-DXd) [Срок оценки: Approximately 2.5 years]
• Participant-reported lung cancer symptoms of non-small cell lung cancer (NSCLC) [Срок оценки: Approximately 2.5 years]
• Participant-reported physical functioning [Срок оценки: Approximately 2.5 years]
• Participant-reported global health status (GHS)/quality of life (QoL) [Срок оценки: Approximately 2.5 years]
• Correlation of TROP2 expression at various cut offs with clinical response [Срок оценки: Approximately 2.5 years]
• Diagnostic development and biomarker assay concordance analysis [Срок оценки: Approximately 2.5 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

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Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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