A Prospective, Single-arm, Multicenter Phase II Clinical Study of Hepatic Arterial Perfusion Chemotherapy (FOLFOX) in Combination With Adebrelimab and Bevacizumab for Potentially Resectable Hepatocellular Carcinoma
Primary liver cancer mainly consists of three different pathologic types: hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and hybrid HCC-ICC, of which HCC accounts for 90%. According to GLOBOCAN 2018 data, liver cancer is the sixth most prevalent tumor in the world, with about 841,100 new liver cancer cases and 781,600 deaths per year globally, which is the second leading cause of tumor deaths in men worldwide. China is a high incidence area of liver cancer, accounting for about 50% of the global incidence and deaths. The treatment of HCC varies according to disease stage, which is based on the BCLC classification system, Child-Pugh liver function rating, and extent of disease. Approximately 30% of HCC cases are diagnosed in the early stages (i.e., BCLC stage 0 or A), and the main treatment options include surgical resection, ablation techniques, and liver transplantation. However, the 5-year recurrence rate remains as high as 70%. The recommended treatment for intermediate stage HCC (i.e., BCLC stage B) is hepatic artery intervention, i.e., transarterial chemoembolization (TACE), but the scope of applicability is limited due to concomitant disease and liver impairment factors, some patients do not derive a survival benefit from it, and patients ultimately progress after treatment and are no longer suitable for further TACE. In recent years, the multi-drug combination therapy of systemic drugs combined with local therapy has also been gradually adopted, and studies have reported the feasibility of target drugs combined with ICI, TACE or HAIC for the treatment of unresectable hepatocellular carcinoma. The therapeutic aim of Adebrelimab (SHR-1316) is to inhibit tumor growth by specifically blocking the binding of PD-1 to PD-L1 and terminating the immunosuppressive signals generated by this receptor on T cells, so that T cells can re-recognize tumor cells and produce killing effects on them. This study proposes an evaluation to explore the efficacy and safety of irinotecan liposome-based hepatic arterial perfusion chemotherapy (FOLFIRI) in combination with adebrelimab and bevacizumab for the treatment of potentially resectable hepatocellular carcinoma.
• patients voluntarily enrolled in the study and signed an informed consent form.
• 18-75 years old, both male and female.
• patients with HCC diagnosed histologically, cytologically, or clinically.
• CNLC-IIb to IIIaHCC (IIIa is limited to combined portal vein branch thrombosis Ching's staging grade I/II) of the Guidelines for the Management of Primary Liver Cancer (2022 edition).
• not have received any prior local and systemic therapy for HCC.
• at least one measurable lesion (the measurable lesion is ≥10 mm in long diameter or ≥15 mm in short diameter of enlarged lymph node on spiral CT scan according to RECISTv1.1).
• Child-Pugh score ≤7.
• ECOG score:0\
• Expected survival ≥12 weeks.
⁃ Vital organs function in accordance with the following requirements (within 7 days prior to initiation of study treatment).
‣ (1) Routine blood tests: (except hemoglobin, which has not been transfused, granulocyte colony-stimulating factor \[G-CSF\], or corrected with medication within 14 days prior to screening): absolute neutrophil count ≥ 1.5 x 109/L; platelets ≥ 75 x 109/L; hemoglobin ≥ 90 g/L.
‣ (2) Biochemical tests: (no albumin transfusion within 14 days prior to screening): serum albumin ≥29g/L; serum total bilirubin ≤1.5×upper limit of normal range (ULN); alanine aminotransferase (ALT), aspartate aminotransferase acid enzyme (AKP) ≤5×ULN; serum creatinine (Cr) ≤1.5ULN or Cr clearance \>50mL/min.
‣ (3) International normalized ratio (INR) ≤ 2.3 or prothrombin time (PT) exceeding the range of normal control ≤ 6 seconds.
‣ (4) Urine protein \<2+ (if urine protein ≥2+, 24-hour (h) urine protein quantification can be performed, and 24-h urine protein quantification \<1.0 g can be enrolled).
‣ 11\. If the patient has active hepatitis B virus (HBV) infection: HBV-deoxyribonucleic acid (DNA) must be \<500 IU/mL (or \<2500 copies/mL if only copies/mL are available at the study center), and has received at least 14 days of anti-HBV treatment prior to the initiation of study treatment (based on the standard of care in the local area, e.g., entecavir) and is willing to be enrolled at the time of study treatment. Patients who are hepatitis C virus (HCV) ribonucleic acid (RNA)-positive must be receiving antiviral therapy according to standard local treatment guidelines and have liver function within CTCAE grade 1 elevation.
‣ 12\. Patients must agree to use contraception for at least 120 days from the date of informed consent until the last dose of study drug. Must have had a negative serum HCG test within 7 days prior to starting study treatment; must not be breastfeeding.