Efficacy Study of Pegylated Recombinant Human Arginase 1 as a Second-line Therapy in Patients With Advanced Liver Cancer

Inclusion Criteria:

• Clinical diagnosis of hepatocellular carcinoma (HCC) according to the European Association for the Study of the Liver (EASL) criteria
• Patients with advanced HCC defined as unresectable disease which is not amenable OR refractory to local-regional therapy OR with extra-hepatic involvement
• Patients have received prior systemic treatment with sorafenib for at least 14 days (not necessarily consecutive), and resulted in either disease progression or intolerance with sorafenib treatment
• Sorafenib must be the last antineoplastic treatment before enrollment
• Patients who are suitable for percutaneous tissue biopsy
• ECOG Performance Status 0-2
• Adequate hematological, renal and hepatic function as assessed by the following blood tests sampled at screening visit
• Life expectancy longer than 12 weeks
• Subjects with at least one measurable lesion assessed by CT scan or other imaging within 4 weeks prior to the first dose of PEG-BCT-100
• Normal ECG
• Patients who give written informed consent prior to any study specific screening procedures with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.

Exclusion Criteria:

• Has received any surgery, loco-ablative, transarterial therapy or radiotherapy ≤ 2 weeks prior to the first dose of PEG-BCT-100
• Has received systemic cancer therapy, e.g. chemotherapy, targeted biologic or enzymes, either approved or investigational, ≤ 2 weeks prior to the first dose of PEG-BCT-100.
• Any toxic effects (except hair loss) of the prior therapy have not been resolved to Grade 2 or less according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events.
• Prior malignancy except cervical carcinoma in situ or treated basal cell carcinoma. Any cancers treated curatively > 5 years prior to study entry are permitted.
• Child-Pugh class of B or C
• Patients with ascites uncontrolled by medication
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.
• Prior treatment with arginine depleting agent.
• Female patients who are pregnant or lactating, or men and women of reproductive potential not willing or not able to employ an effective method of birth control/contraception to prevent pregnancy during treatment and for 6 months after discontinuing study treatment. The definition of effective contraception should be in agreement with local regulation and based on the judgment of the principal investigator or a designated associate.
• A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment.
• Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
• Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
• Subjects, who in the opinion of the Investigator, are unable to comply with the trial treatment and the related trial procedures.