Phase 2 Study of ADI-PEG 20 Plus Lenvatinib Treatment in Subjects With Unresectable Hepatocellular Carcinoma

Inclusion Criteria23

• Prior diagnosis of HCC confirmed by radiology, histology, or cytology.
• Patients were rs-6025211 non-TT with rs9679162 non-GG genotype , or serum arginine level ≥ 84.2 µM with rs9679162 non-GG genotype. Treatment naïve or under Lenvatinib treatment for \< 2 months.
• Measurable disease using RECIST 1.1 (Appendix A). At least 1 measurable lesion must be present.
• Child-Pugh (cirrhosis status) score class A (Appendix C).
• Barcelona Cancer of the Liver (BCLC) stage C (Appendix B).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment (Appendix D).
• Expected survival of at least 3 months.
• Age \>18 years.
• Fully recovered from prior surgery and none within 2 weeks prior to week 1 visit. Liver biopsy for HCC confirmation is allowed.
• Female subjects and male subjects must be asked to use appropriate contraception for both the male and female for the duration of the study. Male partners of female subjects and female partners of male subjects must agree to use two forms of contraception or agree to refrain from intercourse for the duration of the study if they are of childbearing potential. Females of childbearing potential must not be pregnant at the start of the study, and a serum human chorionic gonadotropin (HCG) pregnancy test must be negative before entry into the study. If positive HCG pregnancy test, further evaluation to rule out pregnancy must be performed according to GCP before this subject is deemed eligible. Females not of childbearing potential must be post-menopausal (defined as cessation of regular menstrual period for at least 12 months).
• Informed consent must be obtained prior to study initiation.
• No concurrent investigational studies are allowed.
• Total bilirubin \< 2.5 mg/dL and no evidence of bile obstruction.
• Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 x upper limit of normal range.
• Serum albumin level ≥ 3.0 g/dl.
• Prothrombin time (PT)-international normalized ratio (INR): PT \<3 seconds above control or INR \<1.7.
• Absolute neutrophil count (ANC) \>1,500/µL.
• Platelets \>50,000/µL.
• Serum uric acid ≤ 8 mg/dL (with or without medication control).
• Serum creatinine ≤ 1.5 x the upper limit of normal range, or, if serum creatinine \>1.5 x the upper limit of normal range, then the creatinine clearance must be ≥ 40 mL/min.
• Subjects with active hepatitis B or C on anti-viremic compounds may remain on such treatment, except for interferon.
• Encephalopathy - none or mild (grade 1 or 2, by Child-Pugh classification); lactulose of other supportive care allowed.
• Ascites - absent or slight (by Child-Pugh classification); diuretic therapy allowed.