Regorafenib After Treatment Failure of First Line Immune Checkpoint Inhibitor Treatment in Advanced Hepatocellular Carcinoma Patients

Inclusion Criteria: 1. Voluntarily signed written informed consent form. 2. Age ≥19 years at the time of signing the informed consent form. 3. Histologically or clinically diagnosed hepatocellular carcinoma (HCC) according to the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) guidelines. 4. Disease progression or treatment discontinuation due to toxicity during first-line immune checkpoint inhibitor-based combination therapy (atezolizumab plus bevacizumab, durvalumab plus tremelimumab, or nivolumab plus ipilimumab). 5. At least one measurable target lesion according to RECIST v1.1. 6. Child-Pugh score B (7-8).Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 7. Adequate hematologic and end-organ function defined by the following laboratory results obtained within 14 days prior to the test (or enrollment): * Hemoglobin ≥ 8.5 g/dL * Absolute Neutrophil Count (ANC) ≥1,200/mm³ * Platelet count ≥60,000/µL * Total bilirubin \< 3.5 mg/dL * Serum albumin ≥2.5 g/dL * Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤7 times upper limit of normal (ULN) * Prothrombin time (INR ≤1.8 times ULN) * Serum creatinine ≤2.0 times ULN or calculated creatinine clearance ≥40 mL/min (using the Cockcroft-Gault equation) 10\) Virologic status of hepatitis confirmed and documented by HBV and HCV screening tests.Patients with HBV or HCV infection must receive antiviral therapy according to institutional guidelines. 11\) Women of childbearing potential must agree to remain abstinent or use effective contraception (with an annual failure rate of \< 1%) from the time of signing informed consent until at least 6 months after the last dose of the study drug.Male participants must agree to remain abstinent or use effective contraception (with an annual failure rate of \< 1%) and refrain from sperm donation from the time of signing informed consent until at least 6 months after the last dose of the study drug. Exclusion Criteria: 1. ALBI (Albumin-Bilirubin) grade 3. 2. Fibrolamellar carcinoma or sarcomatoid carcinoma. 3. Prior treatment with regorafenib. 4. Within 2 weeks since the last administration of an immune checkpoint inhibitor. 5. Receipt of any other systemic or locoregional therapy after the failure of first-line immune checkpoint inhibitor-based therapy. 6. History of allogeneic stem cell transplantation or solid organ transplantation. 7. Active brain metastases or leptomeningeal metastases. 8. History of malignancy other than hepatocellular carcinoma (HCC) within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year survival rate \> 90%). 9. Severe cardiovascular disease within 3 months prior to the start of study therapy (e.g., New York Heart Association \[NYHA\] Class II or higher heart disease, myocardial infarction, or cerebrovascular accident); unstable arrhythmia or unstable angina; history of gastrointestinal perforation, fistula, or intra-abdominal abscess within 6 months prior to the start of study therapy; active gastrointestinal disease with a high risk of bleeding or perforation (e.g., peptic ulcer, inflammatory bowel disease, diverticulitis, cholecystitis, acute pancreatitis); untreated high-risk varices or recent history of variceal bleeding (enrollment is permitted only if at least 28 days have passed since stabilization with standard treatment); prolonged QTc interval (\> 450 ms for males, \> 470 ms for females); systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg despite optimal medical therapy; or other significant medical conditions or abnormal findings that, in the opinion of the investigator, may increase the risk associated with study participation. 10. Female participants who are pregnant or breastfeeding, or male or female participants of reproductive potential who are unwilling to use effective contraception from screening until 6 months after the last dose of the study drug. 11. Participants deemed by the investigator to be unlikely to comply with study procedures, restrictions, and requirements. 12. Patients who have received locoregional therapy (e.g., radiofrequency ablation \[RFA\], microwave ablation \[MWA\], transarterial chemoembolization \[TACE\], transarterial radioembolization \[TARE\], transarterial embolization \[TAE\], radiation therapy, etc.) after the discontinuation of immune checkpoint inhibitor-based combination therapy.