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

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.

Eligibility Criteria:
Inclusion Criteria:

* Aged 45-85 years.
* Ability to provide informed consent.
* BMI 16 - \<40.
* Receiving a CT including the thoracic region, within the last 6 months.

Exclusion Criteria:

1. (Anticipated) inability to complete the breath sampling procedure (e.g., inability to maintain adequate ventilation unaided or claustrophobia).
2. Potential subjects who in the opinion of the investigator lack mental capacity.
3. Received an investigational medical product in the context of a Clinical Trial (CTIMP) during the 28 days prior to administration of the (first) probe, or within 5 times the half-life of the investigational medicinal product previously received, whichever is longer.\*
4. Individuals under diagnostic investigation for a potential malignancy other than lung cancer that has not yet reached a conclusive diagnosis\*\*.
5. Individuals with an inconclusive lung abnormality (indeterminate pulmonary nodule) on CT-scan requiring CT-based monitoring rather than biopsy and/or treatment.
6. Documented history of pulmonary surgery or endobronchial interventional procedures other than biopsy, lavage, or bronchial brushings. These include surgical resection, Video Assisted Thoracic Surgery (VATS), bronchial thermoplasty and coiling, airway stenting or other interventional bronchoscopic procedures.
7. Pregnant or breastfeeding women and women of child-bearing potential not using adequate contraceptive methods (Subjects must agree to use contraception for 2 months post last dose).
8. Individuals under investigation for suspicion of lung cancer who are unlikely to receive a definitive tissue diagnosis of lung cancer prior to treatment (e.g. stereotactic ablative radiotherapy without tissue confirmation).

   * Note:

In the case that the participant has taken part in a study with an investigational medicinal product please contact the Owlstone medical monitor for advice.

\*\*Note: Individuals with a confirmed cancer diagnosis ARE eligible (such as a diagnosis of prostate cancer now undergoing hormone therapy). Individual with a previous history of cancer other than lung cancer, including those under active surveillance, ARE eligible. Individuals scheduled to attend a cancer screening program; prostate, breast, lung, colon, ARE eligible.