Phase IIb, Randomized, Active-Controlled, Parallel-Group, Multicenter Clinical Study to Evaluate the Efficacy and Safety of AST-3424 in Patients With AKR1C3-High Expressing Advanced Hepatocellular Carcinoma Who Progressed After Systemic Therapy With Immune Checkpoint Inhibitors
The goal of this clinical trial is to learn if drug AST-3424 works to treat AKR1C3 high expressing advanced hepatocellular carcinoma after failure of systemic therapy with immune checkpoint inhibitors. The main question it aims to answer is: Does AST-3424 prolong survival in patients with AKR1C3-high Expressing advanced Hepatocellular Carcinoma who have progressed after immune checkpoint inhibitors based therapies? Researchers will compare AST-3424 to regorafenib (current optional therapy for target patients) to see if AST-3424 works. Participants will: Receive AST-3424 infusion on Day 1 and Day 8 of each 21-day treatment cycle or take regorafenib once a day on Day 1 -Day 21 of each 28-day treatment cycle.
• Patients with pathologically confirmed advanced hepatocellular carcinoma (HCC).
• Documented disease progression confirmed by medical imaging after failure of prior systemic therapy regimens containing immune checkpoint inhibitors (ICIs).
• Barcelona Clinic Liver Cancer (BCLC) stage B or C; ineligible for or refusing surgical resection or locoregional liver therapies (including transarterial intervention and ablation).
• Child-Pugh class A or B liver function (score ≤ 7), with no history of hepatic encephalopathy.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• At least one measurable extracranial lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Expected survival ≥ 3 months.
• Availability of pathological tissue blocks or sections (including archived samples) for AKR1C3 expression and related biomarker analysis. Immunohistochemistry (IHC) results must confirm high expression of AKR1C3.
• Adequate organ function.
⁃ For subjects positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb):
⁃ HBV DNA level must be \< 2000 IU/mL or 10⁴ copies/mL Subjects must be receiving anti-HBV therapy . This therapy must be maintained throughout the study period and for 6 months after the last dose of study drug.
⁃ For subjects positive for HCV antibody, HCV-RNA level must be below the lower limit of detection (LLOD) of the study center.
⁃ Female subjects of childbearing potential must be non-lactating and have a negative pregnancy test result within 7 days prior to treatment initiation. A positive urine pregnancy test result must be confirmed by a serum pregnancy test.
⁃ Female and male subjects of childbearing potential must agree to use effective contraceptive measures from the time of study enrollment until 6 months after the last dose of study drug.
⁃ Subjects must voluntarily participate in the study, provide written informed consent after a full understanding of the study details, and have good compliance to cooperate with study treatment, observation, and follow-up procedures.