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)
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).
∙ \- 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.