WCLC 2025 - Posters & ePosters-P1.04.54 Breath-based Lung Cancer Detection: Initial Phase 2 Results for D5-Ethyl-β-D-glucuronide (OWL-EVO1) as a Lung Cancer Probe

P1.04.54 Breath-based Lung Cancer Detection: Initial Phase 2 Results for D5-Ethyl-β-D-glucuronide (OWL-EVO1) as a Lung Cancer Probe

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This study reports initial Phase 2 results for OWL-EVO1, an engineered exogenous volatile organic compound (EVOC) probe (D5-ethyl-β-D-glucuronide) administered intravenously, aimed at improving lung cancer detection via breath analysis. OWL-EVO1 targets extracellular β-glucuronidase present in the tumor microenvironment, releasing D5-ethanol, a volatile reporter compound detectable in exhaled breath. Prior Phase 1 work confirmed safety, tolerability, and proof-of-mechanism.<br /><br />In this multicenter, cross-sectional case-control study (EVOLUTION 2, NCT06193239), 187 participants (90 with biopsy-confirmed lung cancer, all stages, and 97 matched controls with similar comorbidities and risk factors) were recruited across seven UK and EU sites. Up to ten breath samples were collected from pre-dose to 180 minutes post-dose and analyzed via gas chromatography-mass spectrometry (GC-MS). <br /><br />Interim analysis led to lowering the OWL-EVO1 dose from 2 mg/kg to 0.8 mg/kg to mitigate off-target probe cleavage causing early-timepoint signal interference. The optimized protocol found best diagnostic differentiation at 130 minutes post-dose. At this timepoint and dose, sensitivity was 65.1% overall, with 69% sensitivity for early-stage lung cancer (Stages 1 and 2), and specificity was 70.3%. Treated patients showed reduced D5-ethanol levels post-treatment, supporting probe signal correlation with cancer presence. <br /><br />No serious adverse events were reported; 10 mild-to-moderate adverse events possibly related to OWL-EVO1 resolved without sequelae.<br /><br />Challenges include false positives likely from systemic off-target cleavage and false negatives potentially due to tumor variability in probe bioavailability and enzyme expression. Future development focuses on an inhaled OWL-EVO1 formulation to deliver higher localized doses directly to lung tumors, aiming to improve sensitivity and reduce off-target signal.<br /><br />This work advances non-invasive, breath-based lung cancer diagnostics potentially offering improved early detection and greater patient compliance compared to existing low-dose CT screening, addressing a critical unmet medical need.

Asset Subtitle

Robert Rintoul

Meta Tag

Speaker Robert Rintoul

Topic Screening and Early Detection

Keywords

OWL-EVO1

volatile organic compound probe

lung cancer detection

breath analysis

β-glucuronidase

D5-ethanol

gas chromatography-mass spectrometry

diagnostic sensitivity

non-invasive diagnostics

early-stage lung cancer