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After confirming full eligibility, individuals will all be administered the OWL-EVO1 probe intravenously.

This includes:

* Patients diagnosed with histopathologically confirmed lung cancer.
* Individuals with a CT-proven absence of lung cancer, including those with relevant comorbidities and risk factors such as smoking, COPD, asthma, extrapulmonary malignant tumours, active lung infection/inflammation and other chronic respiratory diseases.

OWL-EVO1

Liz Thompson

Alice Michael

Jiri Skopek

Dr Marie Drosslerova

Karolina Argay

Dr Ildiko Horvath

Amanda Stone

Zoe Armstrong

Dr Laura Succony

Shilpa Pushpan

Zara Gatt

Professor Philip Crosbie

Rebecca Boyles

Dr Edward Caruana

Lisa Hudig

Bethany Bridgwood

Professor Eleanor Mishra

Maria Lapuente

Dr William Ricketts

Lisa Hurley

Asha Vikraman

Dr Susannah Bloch

Robert Rintoul

The Phase 2a Evolution study aims to assess the diagnostic accuracy of the OWL-EV1 Probe Breath Biopsy Test to differentiate between individuals with lung cancer and relevant contrast groups.

The contrast groups will be representative of the clinical populations in which the test is intended to be used.

Thus, Evolution Phase 2a will be designed as a cross-sectional, case-control trial that will be conducted at various sites, both in the UK and EU.

In Evolution Phase 1, Owlstone Medical demonstrated the safety and tolerability of their Exogenous Volatile Organic Compound (EVOC) Probe. This phase also demonstrated proof of mechanism for the cleavage of the EVOC Probe, D5-ethyl-βD-glucuronide (OWL-EVO1), into D5-ethanol which can be detected on breath. This makes OWL-EVO-1 a promising EVOC Probe for the detection of lung cancer.

The Evolution Phase 2a study will evaluate the diagnostic accuracy of an OWL-EVO1 based breath test for the differentiation of those with histopathologically confirmed lung cancer and relevant contrast groups with a CT-proven absence of lung cancer. These contrast groups will include those with relevant comorbidities, to truly evaluate accuracy and the robustness of test performance.

As a secondary objective, the study aims to define a test protocol that minimises healthcare worker effort, whilst maximising tolerability and diagnosed accuracy for the intended use setting.

This phase intends to recruit up to 150 cases and 200 controls. Both cohorts will be administered the probe intravenously. Multiple breath samples will be collected for up to 180 minutes post-probe infusion, with the cumulative sampling time not exceeding 60 minutes.

The study results will provide valuable insights into the expected test performance as well as optimisation of the test in a clinical pathway.

Participants with and without suspicion of having lung cancer will all receive the same IMP

Diagnostic Accuracy Study for OWL-EVO1 as a Lung Cancer EVOC® Probe (Evolution Phase 2)

Diagnostic Accuracy Study for OWL-EVO1 as a Lung Cancer EVOC® Probe

The primary endpoint is to assess the diagnostic accuracy of the OWL-EVO1 Breath Biopsy test to differentiate between individuals with lung cancer and contrast groups. This will be reported using a Receiver Operator Characteristic Curve, NPV, PPV, Sensitivity, Specificity \& Likelihood Ratio's. Metrics will be reported for overall test performance as well as pre-defined subgroup analyses.

To define a test protocol for breath sampling and the OWL-EVO-1 infusion that achieves the optimal balance between minimising healthcare worker effort, maximising tolerability, and optimising diagnostic accuracy for the intended use setting. This will be in terms of method, timing, posture and duration.

To gain a refined understanding of the safety and tolerability of OWL-EVO1. This will be based on reported Adverse Events associated with probe administration.

Owlstone Ltd

OWL-EVO1 probe will be administered to those who are fully eligible, including those diagnosed with lung cancer and healthy volunteers

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.

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

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

The primary endpoint for the Phase 1a study is safety of OWL-EVO1 being administered to the subjects evaluated through the number of adverse events and whether or not they are related to the administered probe.

To determine the optimal dose(mg/kg) of the OWL- EVO1 breath test which maximizes the discriminative signal between cases and controls

The primary endpoint for the Phase 1b study is to evaluate safety of OWL-EVO1 in healthy subjects and Lung cancer patients.

To determine the optimal timing (minutes) of the OWL- EVO1 breath test which maximizes the discriminative signal between cases and controls

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Diagnostic Accuracy Study for OWL-EVO1 as a Lung Cancer EVOC® Probe (Evolution Phase 2)	NCT06193239	Lung Cancer	OWL-EVO1	45 Years - 85 Years	Owlstone Ltd
Diagnostic Accuracy Study for OWL-EVO1 as a Lung Cancer EVOC® Probe (Evolution Phase 2)	NCT06193239	Lung Cancer	OWL-EVO1	45 Years - 85 Years	Owlstone Ltd
Diagnostic Accuracy Study for OWL-EVO1 as a Lung Cancer EVOC® Probe (Evolution Phase 2)	NCT06193239	Lung Cancer	OWL-EVO1	45 Years - 85 Years	Owlstone Ltd
Safety and Dose Ranging Study for OWL-EVO1 as a Lung Cancer EVOC® Probe (Evolution)	NCT05510674	Lung Cancer	OWL-EVO1	18 Years - 80 Years	Owlstone Ltd
Safety and Dose Ranging Study for OWL-EVO1 as a Lung Cancer EVOC® Probe (Evolution)	NCT05510674	Lung Cancer	OWL-EVO1	18 Years - 80 Years	Owlstone Ltd

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