A Proof-of-concept Study to Assess the Ability of [18F]AH-111585 PET Imaging to Detect Tumours and Angiogenesis

A Phase 2, Open-label, Proof-of-concept Study to Assess the Ability to Detect Tumours and Angiogenesis Via the Expression of ανβ3/5 Integrin Receptors by [18F]AH-111585 PET Imaging

This proof-of-concept study is designed to assess the ability of [18F]AH-111585 PET imaging to detect tumors and angiogenesis. Up to 30 evaluable subjects are planned to be included at up to 2 study centers in the US. Subjects are considered evaluable if they undergo administration of AH-111585 (18F) Injection, dynamic and static PET imaging, and tumor tissue acquisition. The targeted population is adult subjects at initial diagnosis or recurrence with tumors ≥2.5 cm in diameter who are scheduled to undergo resection or biopsy of the tumor as a result of routine clinical treatment. The tumors must belong to one of the following 5 types:

• High-grade glioma, including glioblastoma multiforme, anaplastic astrocytoma, and anaplastic oligodendroglioma
• Lung cancer, including small cell lung cancer and non-small cell lung cancer
• Head and neck (H&N) tumors, including laryngeal squamous cell carcinoma, well-differentiated thyroid and oral cavity carcinoma
• Sarcoma
• Melanoma

Safety will be assessed from the rates of adverse events, changes in vital signs, changes in electrocardiogram (ECG) parameters, changes in physical examination findings, and changes in clinical laboratory findings.

Efficacy will be assessed as the correlations between parameters derived from the PET images and the reference standards. The reference standards will be immunohistology for αvβ3 integrins and other biomarkers specific for oncology and angiogenesis and from the standard of care imaging.

Measures obtained from optional DCE-CT imaging may also be used to compare the uptake and retention of [18F]AH-111585 in tumors obtained from the dynamic PET to assess functional status of the vascular system of the tumor.

Selection of Subjects: The targeted subject population is adult subjects at initial diagnosis or recurrence with tumours ≥2.5 cm in diameter who are scheduled to undergo resection or biopsy of the tumour as a result of routine clinical treatment.

General Inclusion Criteria for all Subjects:

• The subject is ≥18 years old.
• The subject has been diagnostically imaged and is suspected of having a primary or metastatic tumour lesion ≥2.5 cm of one of the following types: high-grade glioma, including glioblastoma multiforme, anaplastic astrocytoma, and anaplastic oligodendroglioma; lung cancer, including small cell lung cancer and non-small cell lung cancer; H&N tumours, including laryngeal squamous cell carcinoma, and well-differentiated thyroid and oral cavity carcinoma; sarcoma; and melanoma.
• The subject is scheduled to undergo resection or biopsy of the ≥2.5 cm target tumour as a result of routine clinical treatment.
• The subject is scheduled to undergo or has received standard of care diagnostic imaging work-up (following the study centre's routine procedures), e.g. CT with or without contrast, MRI with or without contrast, bone scintigraphy, X-ray, or FDG-PET.
• Female subjects need to be either surgically sterile (has had a documented bilateral oophorectomy and/or documented hysterectomy), post menopausal (cessation of menses for more than 1 year), or if of childbearing potential the results of a serum pregnancy test performed within 24 hours must be negative and with the result known before administration of AH-111585 (18F) Injection. Female subjects of reproductive potential should also employ an effective method of birth control. Barrier contraceptives must be used throughout the study in both sexes.
• The subject is able and willing to comply with study procedures, and signed and dated informed consent is obtained.
• The subject has a blood urea nitrogen value and serum creatinine value of ≤1.5 of the upper normal limit.
• The subject has a platelet count of >75,000 x 10^6/L.
• The subject has a haemoglobin value of >9 g/dL.
• The subject has a prothrombin time and an activated partial thromboplastin time and within normal limits.
• The subject has a clinically acceptable (as judged by the investigator) physical examination at screening and is capable of self-care, i.e. Eastern Cooperative Oncology Group performance status is 0 to 2, such that the subject has a high chance to complete the study.
• The subject has not received any anti-angiogenic agents (e.g. bevacizumab, sorafenib, sunitinib) within 10 days prior to PET imaging.
• The subject has had no open wounds within 10 days prior to study entry.
• The chosen target tumour is not within the liver.

Inclusion Criteria Specific for Subjects with High-grade Glioma:

• The subject is suspected of having supratentorial malignant primary glioma (by biopsy or presenting MRI characteristics as determined by the subject's clinician) requiring further surgical resection as part of the recommended treatment plan for their newly diagnosed disease. These gliomas include glioblastoma multiforme, anaplastic astrocytoma, and anaplastic oligodendroglioma.
• The subject has undergone recent biopsy of newly diagnosed high-grade glioma, has recovered from the effects of surgical biopsy, and baseline on-study MRI/CT is performed within 14 days of entry into the study.

Exclusion Criteria:

• The subject is lactating.
• The subject is being treated with heparin or coumadin.
• The subject has received another investigational medicinal product (IMP) within 14 days before, or will receive an IMP within 1 week after administration of AH-111585 (18F) Injection.
• The subject was previously included in this study.
• The subject experienced substantial changes in their medical status before all essential study procedures (including all imaging procedures and surgical excision or biopsy) are performed.
• The subject has any contraindication to any of the study procedures, products used or its constituents (e.g. X-ray contrast media).
• The subject has known hyper- or hypo-coagulation syndromes. Such coagulopathies include but are not limited to Von Willebrand disease, Protein C deficiency, Protein S deficiency, Hemophilia A/B/C, Factor-V Leiden, and Bernard-Soulier syndrome.
• The subject is unable to lie down for 125 minutes.
• The subject suffers from claustrophobia.
• The subject has known diagnosis of human immunodeficiency virus (HIV) infection.
• The subject has known diagnosis of hepatitis B or C infection.
• The subject has known diagnosis of mental incapacitation and it affects their ability to consent.
• The subject has been diagnosed with a primary or metastatic tumour lesion <2.5 cm.