The goal of this investigator-initiated, a single-arm, open-label, pilot study is to investigate the safety, tolerability, and efficacy of intravenous HNF4α srRNA treatment in subjects with advanced Intrahepatic Cholangiocarcinoma (ICC).
Condition of disease: advanced intrahepatic cholangiocarcinoma Intervention： HNF4α srRNA will be administered intravenously for the treatment of ICC. The dosing regimen is planned for a second dose 14 ± 3 days post-initial treatment, followed by subsequent treatments every 28 ± 7 days, with adjustments made based on patient tolerance and therapeutic response. This is a dose escalation assay employing a i3+3 design to assess escalating HNF4α srRNA dosages: 25 μg, 50 μg, and 100 μg. Post-initial dose, a 14-day dose-limiting toxicities (DLT) observation will evaluate tolerability and safety, guiding dose adjustments or selection of the Recommended Dose (RD) for the expansion phase. Cohorts may include up to 9 participants, adjusted for safety.
Drug: HNF4α srRNA, a drug specifically designed to target liver cancer cells and facilitate the expression of HNF4α.
According to Amendment 1, patients who have received at least 4 cycles of HNF4α srRNA therapy and have a tumor assessment of SD (stable disease) or PD (progressive disease) per RECIST v1.1 criteria may, after a comprehensive evaluation by the investigator considering the patient's treatment history and the current safety and efficacy data of HNF4α srRNA, continue HNF4α srRNA at the same dose, or have their dose adjusted, in combination with immunotherapy, targeted therapy, or chemotherapy.
Males or females, aged 18 years or older.
Histologically or cytologically confirmed intrahepatic cholangiocarcinoma patients.
Patients with intrahepatic cholangiocarcinoma not suitable for surgical resection, liver transplantation, or ablation therapy, or those with post-surgical recurrence and/or metastasis.
Patients not suitable for local or systemic treatment, or those who have progressed after at least one chemotherapy regimen containing gemcitabine/fluoropyrimidine/platinum, etc..
Patients with any of the following criteria were excluded from participation in this study
Inadequate liver function：Albumin (ALB) < 25 g/L, or total bilirubin > 5 × the upper limit of normal (ULN), or aspartate aminotransferase (AST), alkaline phosphatase (ALP), or alanine aminotransferase (ALT) >10 × ULN.
Inadequate renal function defined as creatinine >1.5 × ULN or calculated creatinine clearance < 40 mL/min.
Absolute neutrophil count (ANC) < 1.0×109/L, or Platelets < 30×109/L, or Hemoglobin < 8.5 g/dL.