Datopotamab Deruxtecan mostra miglioramento significativo della sopravvivenza nei pazienti con carcinoma polmonare non a piccole cellule ad istologia non squamosa in stadio avanzato
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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 31st, 2024) or ESMO’24 (intent to submit LBA May 7th, 2024; LBA deadline Aug 7th, 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
- mPFS (mos): 4.4 vs 3.7 mo (HR=0.75)
- 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+)