Safety and Dose Ranging Study for OWL-EVO1 as a Lung Cancer EVOC® Probe (Evolution)

The Evolution study is a phase 1a and 1b study evaluating the safety and pharmacokinetics of D5- ethyl-βGlucuronide as well as the target dose for the probe to maximize the difference between controls and subjects with lung cancer. The phase 1a study will be designed as a single ascending dose study in healthy volunteers and will be conducted in a phase 1 trial unit with a primary objective to assess safety of the probe. A subsequent phase 1b study will be conducted at clinical sites and will aim to find the optimal dosing and breath sampling protocol to maximize the accuracy of the breath test. Evolution Phase 1 is a multicentre study; Phase 1a will be conducted at a Phase 1 facility in Belgium and Phase 1b will be conducted in the UK.

Owlstone has recently pioneered the EVOC approach which enables active investigation of disease specific pathways by administering probe compounds to patients and measure its signal on breath. In the Evolution study, Owlstone Medical aims to evaluate one such EVOC probe strategy based on the administration of the probe OWL-EVO1. The Evolution study consist of phase 1a, in which the safety and pharmacokinetics of OWL-EVO1 are assessed; in this part of the study up to 21 healthy volunteers will be recruited. The probe will be administered for the first time in humans in a single ascending dose design. Five different doses of the probe are planned to be administered across 5 different cohorts. This part of the study will be conducted at a Phase 1 unit in Belgium. Participating subjects will be administered a dose of the EVOC probe; up to 8 breath samples, using Owlstone's RECIVA, will be collected in a 24h wash-out. In the subsequent Phase 1b, research will aim to identify the most optimal dose and timing of the breath test to maximise the discriminative signal between lung cancer patients (cases) and healthy controls. Up to 50 cases and 50 controls will be recruited in selected sites in the UK. The Phase 1b has been designed as an adaptive trial design. Participating subjects will be administered the probe and will provide up to 7 breath samples over a 240 minute wash-out. This study is intended to provide proof of concept for the use of OWL-EVO1 as a probe for breath-based detection of lung cancer. This will be an important step towards creating a breath-based screening approach for lung cancer.