Datopotamab Deruxtecan mostra miglioramento significativo della sopravvivenza nei pazienti con carcinoma polmonare non a piccole cellule ad istologia non squamosa in stadio avanzato

Nello studio di fase 3 TROPION-LUNG 01 Datopotamab Deruxtecan mostra un miglioramento clinicamente significativo della sopravvivenza globale nei pazienti con carcinoma polmonare non a piccole cellule ad istologia non squamosa in stadio avanzato -

Nella popolazione complessiva dello studio di fase 3 TROPION-Lung01, i risultati di sopravvivenza globale hanno favorito numericamente datopotamab deruxtecan di Daiichi Sankyo e AstraZeneca rispetto alla chemioterapia, pur non raggiungendo la significatività statistica. 

TROPION-Lung01 aveva precedentemente raggiunto il primo dei due endpoint indipendenti primari di sopravvivenza libera da progressione nella popolazione complessiva dello studio.

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Assessment

• Dato-DXd is currently undergoing regulatory review after filing acceptances from both the FDA and EMA and has potential to be first-to-market in 2L+ mNSCLC
  • Dato-DXd PDUFA date is December 20, 2024
• No new data was presented in the announcement from the full analysis dataset, and the announcement neither confirms nor denies whether Dato-DXd should receive approval with the FDA and EMA in the pre-specified but unpowered Nsq subgroup
  • AZ/Daiichi management argue that Dato-DXd is fileable based on the statistically significant benefit in TROPION-Lung01’s dual primary endpoint of PFS
  • Additionally, management argued that the results in the Nsq population were clinically meaningful due to OS benefit, PFS benefit, more than doubling of ORR, and prolonged DoR when compared to docetaxel
• The timing of the Dato-DXd OS full analysis dataset would allow AZ/Daiichi to present the data at either WCLC’24 (LBA deadline Jul 31^st, 2024) or ESMO’24 (intent to submit LBA May 7^th, 2024; LBA deadline Aug 7^th, 2024)

• ASCO presentations with Dato-DXd:
  • Datopotamab deruxtecan (Dato-DXd) plus pembrolizumab (pembro) with or without platinum chemotherapy (Pt-CT) as first-line (1L) therapy for advanced non-small cell lung cancer (aNSCLC): Subgroup analysis from TROPION-Lung02.
  • ICARUS-LUNG01: A phase 2 study of datopotamab deruxtecan (Dato-DXd) in patients with previously treated advanced non-small cell lung cancer (NSCLC), with sequential tissue biopsies and biomarkers analysis to predict treatment outcome.
  • Analysis of drug-related interstitial lung disease (ILD) inpatients (pts) treated with datopotamab deruxtecan (Dato-DXd).
  • Datopotamab deruxtecan (Dato-DXd) in Chinese patients (pts) with advanced or metastatic non-small cell lung cancer (NSCLC): Results from the phase 1/2 TROPION-PanTumor02 study
  • Intracranial efficacy of datopotamab deruxtecan (Dato-DXd) in patients (pts) with previously treated advanced/metastatic non-small cell lung cancer (a/m NSCLC) with actionable genomic alterations (AGA): Results from TROPION-Lung05
  • A phase 1b, multicenter, open-label study of valemetostat in combination with DXd antibody drug conjugates (ADCs), trastuzumab deruxtecan (T-DXd) or datopotamab deruxtecan (Dato-DXd), in patients with solid tumors.
• Results from the P3 TROPION-Lung01 were presented at ESMO’23 and followed up with Nsq-only data at ELCC’24
  • P3 TROPION-Lung01 (NCT04656652): Dato-DXd (TROP2 ADC) vs docetaxel in 2L/3L mNSCLC with prior IO and chemo
  • N=604 
  • 1EP: PFS and OS
  • 2EP: ORR, DOR, AEs
  • Efficacy (Dato-DXd vs. docetaxel)
    • mPFS (mos): 4.4 vs 3.7 mo (HR=0.75) 
      • Nsq: 5.5 vs 3.6 mo (HR=0.63) 
      • Sq: 2.8 vs 3.9 mo (HR=1.38) 
    • mOS (mos): 12.4 vs 11.0 mo (HR=0.90; interim analysis) 
      • Nsq: 13.4 vs 11.4 mo (HR=0.77, ELCC’24)
      • Sq HR=1.32 
    • ORR: 26% vs 13% 
      • Nsq: 31% vs 13% 
      • Sq: 9% vs 13% 
    • DoR: 7.1 vs 5.6 mo
      • Nsq: 7.7 vs 5.6 mo
      • Sq: 5.9 vs 8.1 mo
  • Safety (Dato-DXd vs. docetaxel) 
    • GR 3+ TRAEs: 25% vs 41% 
    • TRAES associated with 
      • Dose reduction: 20% vs 29% 
      • Discontinuation: 8% vs 12% 
      • Death: 1% vs 1% 
    • AEs of special interest: 
      • ILD/pneumonitis: 8% (Gr3+ 3%, Gr5 2% [7 pt deaths]) vs. 4% (Gr3+ 1%, Gr5 0.3%[1 pt death]) 
      • Mucositis/stomatitis: 54% (Gr3+ 6%) vs. 20% (Gr3+ 1%) 
      • Anemia: 15% (Gr3+ 4%) 
      • Ocular surface toxicity: 19% (Gr3+ 2%) vs. 9% (Gr3+ 0%) 
      • IRRs: 8% (1 patient Gr3+) 

Press Release