A Prospective, Open-label, Single-arm, Phase 2 Study of Hepatic Arterial Infusion Chemotherapy Combined With Lenvatinib and Cadonilimab as Conversion Therapy for Initially Unresectable Hepatocellular Carcinoma
This is an open-label, single-arm, phase 2 study evaluating hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and cadonilimab as conversion therapy for initially unresectable hepatocellular carcinoma (HCC). The primary objective is to assess the conversion rate, defined as the proportion of participants who are deemed amenable to curative-intent treatment by the multidisciplinary team (MDT), including R0 resection, curative ablation, or liver transplantation, after study treatment. Secondary objectives include curative-intent intervention rate, tumor response, survival outcomes, safety, pathological response, and exploratory tissue and blood biomarkers.
• Hepatocellular carcinoma proven on biopsy or confirmed by radiological hallmarks according to the American Association for the Study of Liver Diseases (AASLD) or the European Association for the Study of the Liver (EASL) guidelines.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Not suitable for curative-intent treatment (including radical hepatic resection, liver transplantation, or curative ablation) after evaluation by the hepatobiliary tumor MDT expert group. Specifically, any of the following conditions are met:
‣ R0 resection is not feasible.
⁃ In participants without cirrhosis, the volume of normal liver parenchyma is less than 30% of the total liver volume; or in participants with cirrhosis, the volume of normal liver parenchyma is less than 40% of the total liver volume; or ICG-R15 \>15%.
⁃ BCLC stage B or C.
• No prior systemic anti-tumor treatment for hepatocellular carcinoma before the first dose.
• According to RECIST version 1.1, at least 1 measurable lesion, or a measurable lesion that has clearly progressed after local treatment.
• Participants with portal vein tumor thrombus (PVTT):
‣ Chen's group A and B, or Cheng's type I-III, can be enrolled.
⁃ Cheng's type IV, defined as superior mesenteric vein tumor thrombus, cannot be enrolled.
• Participants with hepatic vein tumor thrombus:
‣ VV1 and VV2 can be enrolled.
⁃ VV3, or Sakamoto type I (inferior vena cava tumor thrombus), can also be enrolled.
⁃ Sakamoto type II (inferior vena cava tumor thrombus extending above the diaphragm) or Sakamoto type III (inferior vena cava tumor thrombus reaching the right atrium) cannot be enrolled.
• Participants with oligometastases outside the liver can be enrolled. Oligometastases are defined as up to three metastatic lesions in a maximum of two organs, with the largest diameter ≤3 cm.
• Child-Pugh score ≤7.
• Adequate organ and bone marrow function within 7 days before enrollment:
‣ Absolute neutrophil count ≥1.5×10\^9/L; platelet count ≥75×10\^9/L; hemoglobin ≥9.0 g/dL.
⁃ Total bilirubin ≤2× upper limit of normal (ULN); ALT and AST ≤5× ULN; serum albumin ≥28 g/L; alkaline phosphatase ≤5× ULN.
⁃ Serum creatinine ≤1.5× ULN or creatinine clearance ≥50 mL/min; urine protein \<2+; if urine protein ≥2+, 24-hour urinary protein must be \<1 g.
⁃ INR ≤2.3 or prothrombin time prolongation ≤6 seconds.
• Estimated life expectancy ≥12 weeks.
• Female participants of childbearing potential, or male participants whose partners are of childbearing potential, must agree to use effective contraception during study treatment and for 6 months after the last dose.
• Signed written informed consent and ability to comply with study visits and procedures.