Although immunotherapy-based therapies (including targeted-immunotherapy or dual-immunotherapy protocols) have become the first-line standard treatment for advanced hepatocellular carcinoma (HCC), there remains a lack of high-level evidence to guide the selection of second-line therapies following progression in immune checkpoint inhibitors (ICIs). Additionally, direct comparative data are scarce for combination treatment modalities such as "continuation of the original first-line regimen with added agents" or "switching to agents with different mechanisms".

To address this clinical need and explore novel second-line treatment strategies for advanced HCC, we plan to conduct an exploratory clinical trial to investigate the efficacy and safety comparison between intensified therapy (plus lenvatinib) and conversion therapy (regorafenib combined with PD-1 inhibitor) for advanced hepatocellular carcinoma after failure of fFirst-line bevacizumab plus sintilimab.

Inclusion Criteria:

1. Diagnosed with hepatocellular carcinoma (HCC) based on histological or clinical diagnostic criteria;
2. Classified as unresectable HCC following multidisciplinary assessment;
3. Presence of at least one tumor lesion measurable according to EASL criteria;
4. Child-Pugh liver function class A/B, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score 0-2;
5. Disease progression confirmed by CT/MRI and evaluated according to modified RECIST (mRECIST)/RECIST v1.1 criteria after ≥2 cycles of first-line therapy with bevacizumab (15 mg/kg intravenous infusion, once every 3 weeks) combined with sintilimab (200 mg intravenous infusion, once every 3 weeks);
6. Received ≥2 cycles of post-progression treatment with bevacizumab plus sintilimab, lenvatinib, or regorafenib combined with PD-1 inhibitors;
7. Age ≥18 and ≤75 years;
8. Capability to comprehend the study protocol and provide written informed consent;
9. Laboratory parameters: hemoglobin(Hb) ≥8.5 g/dL, white blood cell (WBC) count >2000/mm³, platelet (PLT) count ≥75,000/mm³, absolute neutrophil count (ANC) >1500/mm³, total bilirubin ≤30 μmol/L, serum albumin ≥30 g/L, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 times the upper limit of normal (ULN), serum creatinine ≤1.5 times ULN, international normalized ratio (INR) ≤1.5, prothrombin time (PT) ≤18 seconds;
10. Availability of complete baseline data, treatment records, and follow-up data (including imaging assessments, laboratory tests, and clinical documentation).

Exclusion Criteria:

1. Life expectancy ≤2 months;
2. Presence of intrahepatic cholangiocarcinoma, mixed hepatocellular-cholangiocarcinoma, or other non-HCC malignancies;
3. Active concurrent malignancy or severe comorbid conditions;
4. First-line treatment with other anticancer therapies (chemotherapy, radiotherapy, surgery, or other interventions) concurrently;
5. Pregnancy or lactation;
6. Known hypersensitivity to study drugs;
7. Clinically significant gastrointestinal bleeding within 30 days prior to enrollment;
8. Refusal to comply with study and/or follow-up procedures.