Regorafenib After Failure of Lenvatinib in Patients With Unresectable HCC: The RELEVANT-HCC Trial

Prior treatment

• Prior treatment with regorafenib.
• 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); uncontrolled serious medical comorbidities, including unstable arrhythmia or unstable angina; or other significant medical conditions or abnormal findings that, in the opinion of the investigator, may increase the risk associated with study participation.
• 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.
• 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 discontinuation of lenvatinib treatment.

Other illness

• History of allogeneic stem cell transplantation or solid organ transplantation.
• 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%).

Lab values

• Albumin-bilirubin (ALBI) grade 3.

Other

• Fibrolamellar carcinoma or sarcomatoid carcinoma.
• Active brain metastases or leptomeningeal metastases.
• Participants deemed by the investigator to be unlikely to comply with study procedures, restrictions, and requirements.

• Signed informed consent form.
• Age ≥ 19 years at the time of signing the informed consent form.
• Diagnosis of hepatocellular carcinoma (HCC) confirmed histologically or clinically according to the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) guidelines.
• Patients with unresectable HCC who have experienced disease progression or treatment discontinuation due to toxicity during prior treatment with lenvatinib.
• Presence of at least one measurable target lesion according to RECIST v1.1.
• Child-Pugh classification A or B7 (score 7).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Adequate hematologic and end-organ function defined by the following laboratory test results obtained within 14 days prior to testing (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
  • AST and ALT ≤ 7 × upper limit of normal (ULN)
  • Prothrombin time (INR ≤ 1.8 × ULN)
  • Serum creatinine ≤ 2.0 × ULN or calculated creatinine clearance ≥ 40 mL/min (Cockcroft-Gault equation)
• Virological status of hepatitis confirmed and recorded through HBV and HCV screening.
  • Participants with HBV or HCV infection must be receiving antiviral therapy according to institutional guidelines.
• Women of childbearing potential must agree to maintain abstinence or use effective contraception (with an annual failure rate of \< 1%) from the time of signing the informed consent until at least 6 months after the last dose of the study drug. Male participants must agree to maintain abstinence or use effective contraception (with an annual failure rate of \< 1%) and refrain from sperm donation from the time of signing the informed consent until at least 6 months after the last dose of the study drug.