A Phase II, Open-Label Trial Evaluating GV1001 in Advanced Hepatocellular Carcinoma.

Inclusion criteria

• Hepatocellular carcinoma diagnosis fulfilling one of the following criteria (as per the American Association for the Study of Liver Diseases [AASLD] guidelines, see Appendix 5):

• Nodule in a cirrhotic or non-cirrhotic liver with a biopsy showing HCC;
• Nodule in cirrhotic liver where no biopsy is performed:

• Nodules between 1-2 cm in a cirrhotic liver with a typical coincidal vascular pattern of HCC (i.e. hypervascular with washout in the portal/venous phase) in two dynamic studies: either CT scan, contrast ultrasound or MRI with contrast.
• Nodule larger than 2 cm in a cirrhotic liver with a typical vascular pattern of HCC on a dynamic imaging technique.

Please note: HCC in a non-cirrhotic liver can only be diagnosed with a biopsy showing HCC.

• Measurable disease according to modified RECIST (see Appendix 7).
• At least one treatment-naïve target lesion (treatment-naïve being defined as not having been treated with local therapy, such as surgery, radiation therapy, hepatic arterial embolisation, chemoembolisation, radio-frequency ablation or cryo-ablation).
• Barcelona Clinic Liver Cancer (BCLC) stage A, B or C (see Appendix 6) (Stage D is excluded).
• Child-Pugh stage A (see Appendix 8).
• Male or female aged 18 years or older.
• Adequate haematological parameters, as demonstrated by:

• Haemoglobin greater than or equal to 9.0 g/dL (SI units: 5.6 mmol/L);
• WBC greater than or equal to 3.0 x 109/L;
• Platelets greater than or equal to 75 x 109/L.
• ALT and AST ≤ 5 times the upper limit of normal.
• Bilirubin < 2 mg/dL.
• Serum creatinine smaller than or equal to 1.5 mg/dL (SI units: 132 µmol/L).
• Performance status ECOG 0 or 1.
• Minimum life expectancy of 3 months at screening.
• Written informed consent given prior to any study specific procedures.

Exclusion criteria

• HCC amenable to curative treatment or transplantation.
• History of other malignancies in the last 5 years (10 years in the case of breast cancer), except for adequately treated non-melanoma skin cancers (Basal Cell Carcinoma, Squamous Cell Carcinoma) and carcinoma in situ of the cervix.
• Known history of or co-existing autoimmune disease.
• Known Central Nervous System (CNS) metastases.
• Known history of human immunodeficiency virus (HIV).
• Any medical condition that, in the opinion of the Investigator, may compromise the compliance of the patient to receive study treatment and follow study procedures.
• Treatment with any other IMP within 4 weeks prior to cyclophosphamide administration at Day -3.
• Known sensitivity to any components of cyclophosphamide, GV1001 or GM-CSF.
• Concomitant treatment with the following within 4 weeks of pre-treatment with cyclophosphamide:

• Anti-tumour treatment (including radiotherapy, chemotherapy, immunotherapy, endocrine therapy, cytokines, interferons, protease inhibitors, and gene therapy) and vaccines.
• Chronic corticosteroids (inhaled and topical steroids are permitted including low dose steroids at non-immunosuppressive doses e.g. 15 mg prednisolone daily for up to 7 days).
• Herbal medicine either containing hypericum perforacum (e.g., St Johns Wort) or claiming to have anti-tumour effects (e.g., Iscador).
• Pregnancy or lactation.
• Women of childbearing potential not using reliable and adequate contraceptive methods, defined as the use of oral, implanted, injectable, mechanical or barrier products for the prevention of pregnancy; or women who are practising abstinence; or where the partner is sterile, for example a vasectomy.
• Unable for any other reason to comply with the protocol (treatment or assessments).