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

This is an interventional diagnostic trial for Lung Cancer Read More

Inclusion Criteria:Phase 1a

1. Aged 18-70 years
2. Ability to provide written informed consent
3. Weight not exceeding 100 kg
4. Body Mass Index (BMI) between 18.5 and 30
5. Meeting criteria for fitness for infusion as detailed in Section 10.3.1 - Safety Assessment Phase 1a and b Study

Inclusion Criteria: Phase 1b

1. Aged 55-80 years
2. Ability to provide informed consent
3. Weight not exceeding 100kg
4. BMI between 18.5 and 30.0
5. Meeting criteria for fitness for infusion as detailed in Section 10.3.1 - Safety Assessment Phase 1a and b Study

Control specific inclusion criteria - phase 1b ONLY 1. healthy as per medical records and clinical assessment at screening

Lung cancer subject specific inclusion criteria - Phase 1b ONLY

1. Tumor Node Metastasis (TNM) stage I, II, III or IV primary lung cancer.
2. Multi-Disciplinary Team (MDT) diagnosis of an invasive malignant lung tumor. This evaluation should integrate data from the clinical, imaging and pathology work-up.

Exclusion Criteria:

Phase 1a and 1b

1. (Anticipated) inability to complete the breath sampling procedure due to e.g., inability to maintain adequate ventilation unaided or claustrophobia.
2. Received an investigational medical product in the context of a Clinical Trial (CTIMP)during the 28 days prior to first probe administration.
3. History of alcohol dependence or diagnosis of alcoholism.

4. Subjects known to suffer from an unstable systemic, inflammatory, infectious, or neoplastic condition. Specifically, subjects should be excluded if:

   4.1. Currently in the process of investigation for a potential malignancy. 4.2. Any history of cancer or indeterminate lung nodule. 4.3. Known active bacterial, fungal, or viral infection including but not limited to upper respiratory tract infection, tuberculosis, pneumonia, cystitis, pyelonephritis, active gastritis under medical treatment, prostatitis, or viral hepatitis. Patients can be recruited after being symptom free for at least 2 weeks for mild infections or 6 weeks if admitted to the hospital and/or treated with intravenous antibiotics. For the avoidance of doubt: Any skin infection without subcutaneous involvement (such as acne vulgaris) is permissible in the study.

   4.4. Clinically diagnosed presence of rheumatoid arthritis. Osteoarthritis, spondylarthritis and sports injuries are NOT exclusion criteria 28.

   4.5. Documented history of a clinically important lung condition including asthma, Chronic Obstructive Pulmonary Disease (COPD), α1- antitrypsin deficiency, moderate to severe bronchiectasis and/or exacerbation of bronchiectasis requiring treatment, cystic fibrosis, primary ciliary dyskinesia, allergic bronchopulmonary aspergillosis/mycosis, moderate to severe pulmonary fibrosis or hypersensitivity pneumonitis.

   4.6. Known renal function impairment (eGFR 45ml/min or less). 4.7. Known liver function impairment with test results being above 1.5 times the normal upper limit.

   4.8. Pregnant or breastfeeding women and women of child-bearing potential not using adequate contraceptive methods. Please refer to Appendix 1 for an overview of highly effective contraceptive measures that are accepted adequate contraceptive methods for this study. A woman of childbearing potential is a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient any hospitalization during the 6 weeks prior to first probe administration.

5. Known glucose intolerance or Diabetes Mellitus.
6. Self-reported immunocompromised patients: specifically, patients with Acquired Immune Deficiency Syndrome (AIDS), inborn or acquired severe immunodeficiency including those caused by pharmacological treatment.
7. Documented history of pulmonary surgery or endobronchial interventional procedures other than biopsy, lavage, or bronchial brushings. These include surgical resection,

Control specific exclusion criteria - phase 1b ONLY

1. Under clinical investigation for lung cancer
2. Current smoker
3. At high risk of lung cancer: Aged 55-70 with >30 packyears smoking history, either a current smoker or quit smoking in the past 15 years as per USPSTF risk-criteria30.

Lung cancer subject specific exclusion criteria - phase 1b ONLY

1. Initiation of treatment for lung cancer prior to providing final breath sample.