A Phase I, Single-arm, Open-label, Dose-escalation, Safety and Pharmacokinetic Study of AU409 Capsule in Advanced Hepatocellular Carcinoma Patients Who Failed Standard Treatment
This study is a Phase I, dose-escalation study of AU409 in advanced hepatocellular carcinoma patients who failed standard treatment. A '3+3' dose-escalation design will be utilized to gradually increase the dose of AU409, aiming to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor efficacy of multi-dose AU409 in patients with advanced HCC.
• Male or female of 18-75 (inclusive) years of age.
• Patients with histologically and/or cytologically and/or radiologically confirmed advanced (unresectable or metastatic) hepatocellular carcinoma (HCC) that have failed any of standard treatment (including Immunotherapies and/or Tyrosine Kinase Inhibitor therapies, or Oxaliplatin-based systemic chemotherapies), recurrence, or are intolerant.
• Before treatment initiation, patients must have previously completed chemotherapy, radiotherapy, interventional therapy for more than 4 weeks (except palliative radiotherapy for bone metastasis). And all treatment-related toxicities (except hair loss, pigmentation, and chemotherapy-related neurotoxicities, etc.) have recovered (≤ level 1 or baseline level).
• Have at least one evaluable disease lesion based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST).
• ECOG score of 0 or 1.
• Patients with Child Pugh class A or some class B (≤7 and no hepatic encephalopathy).
• Have a life expectancy of \>12 weeks.
• Able to be orally administered.
• Laboratory examinations must meet the following criteria within 7 days before treatment initiation:
‣ Absolute neutrophil count（ANC）≥1.5 × 109/L，platelets（PLT） count ≥75 × 109/L，hemoglobin（HGB）≥90 g/L，and patients are not allowed to receive blood transfusion or other haematopoietic growth factors within 14 days before treatment initiation.
⁃ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be ≤5.0×upper limit of normal (ULN).
⁃ Total bilirubin (TBIL) ≤1.5×ULN.
⁃ Ablumin (ALB) ≥28g/L.
⁃ Serum creatinine (CRE) ≤1.0×ULN, creatinine clearance rate (CCR) ≥60 mL/min (Cockcroft-Gault equation).
⁃ International normalized ratio（INR）≤1.5，prothrombin time (PT) ≤1.5×ULN.
⁃ Have a negative serum pregnancy test for premenopausal women (postmenopausal women who have been menopausal for at least 12 months are considered as infertile). For male patients (including male patients' female spouses of child-bearing potential) and female patients of child-bearing potential must be contraceptive throughout the study and within the 6 months following the last dose of AU409.
⁃ Patients voluntarily give written informed consent form (ICF).