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

"Heptovax" - A Phase II, Open-Label Trial Evaluating the Safety and Efficacy of GV1001 in Advanced Hepatocellular Carcinoma.

The purpose of this study is to investigate the efficacy of GV1001 in locally advanced or metastatic HCC. Also the safety of GV1001 and immunogenicity will be evaluated.

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):

  1. Nodule in a cirrhotic or non-cirrhotic liver with a biopsy showing HCC;

  2. 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).