A Dose Ascending, Open Phase I Clinical Study to Evaluate the Safety, Tolerability , Pharmacokinetics Characteristics and Preliminary Effectiveness of VG161 in Subjects with Advanced Primary Liver Cancer
VG161 is a recombinant human-IL12/15/PDL1B oncolytic HSV-1 Injectable. This phase I study will be conducted in HSV-seropositive subjects with advanced primary liver cancer that are refractory to conventional therapies. This is an open label study and it's divided into two parts. Part 1: This part is ascending dose design to determine the safety and tolerability of VG161 and find recommended dose of VG161. Part 2: This part is extended dose design to determine the effectiveness of VG161.
⁃ According to 'The Diagnostic and Therapeutic Criteria for Primary Liver Cancer' (NMPA, 2019 Edition), subject with advanced primary hepatocellular carcinoma, intrahepatic cholangiocarcinoma, combined hepatocellular which is refractory/relapsed after and/or intolerant of standard therapies or for which no standard therapy exists. For the second stage of Simon\'s two-stage in part 2, only patients with advanced primary hepatocellular carcinoma will be enrolled.
⁃ There are tumor lesions intrahepatic and / or extrahepatic metastases that can be injected under B ultrasound and meet the volume requirements of the current dose group, and the longest diameter of injectable tumor lesion \>1.5cm（or the shortest diameter of lymph node lesions）
⁃ Eastern Cooperative Oncology Group (ECOG) scores 0 or 1.
⁃ Life expectancy is at least 3 months.
⁃ Required organ function:
‣ 1\) Hematology blood (no blood transfusion or colony stimulating factor treatment within 14 days): absolute neutrophil count (ANC)≥1.5×10\^9L, platelets (PLT)≥75×10\^9L, hemoglobin (Hb)≥85g/L; 2) Liver function: Total Serum bilirubin (TBIL)≤1.5×ULN (the upper limit of the reference range), Alanine aminotransferase (ALT)≤5×ULN, aspartate aminotransferase (AST)≤5×ULN; 3)Child-Pugh A-B level; 4) Renal function: Serum creatinine≤1.5×ULN, and creatinine clearance≥45 ml/min (calculated per Cockcroft-Gault formula); 5) Coagulation function: activated partial thromboplastin time (APTT)≤1.5×ULN, prothrombin time(PT) ≤1.5×ULN, international standardized ratio (INR)≤1.5×ULN.
‣ 6\. Subjects who are HBV-DNA negative; or HBV-DNA positive are required to receive treatment in accordance with the 'Guidelines for the prevention and treatment of chronic hepatitis B' (2019 Edition) or clinical practice.
• Subjects of childbearing potential (male and female) must agree to use a reliable contraceptive method (hormone or barrier method or abstinence) during the study and for at least 90 days following the last dose; females of childbearing potential must have a negative blood pregnancy test within 7 days of study enrollment.
• Signed written informed consent.