Intensified versus conversion therapy for advanced liver cancer after first-line bevacizumab plus sintilimab fails
Efficacy and Safety Comparison Between Intensified Therapy (Plus Lenvatinib) and Conversion Therapy (Regorafenib Combined With PD-(L)1 Inhibitor) For Advanced Hepatocellular Carcinoma After Failure of First-line Bevacizumab Plus Sintilimab: A Prospective, Randomized, Two-Cohort, Phase II Study
This study tests whether adding lenvatinib or switching to regorafenib plus a PD-1 blocker works better and is safe for adults with advanced hepatocellular carcinoma whose cancer progressed after first-line bevacizumab plus sintilimab.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 80 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Sun Yat-sen University Academic / other |
| Drugs / interventions | bevacizumab, sintilimab, lenvatinib, chemotherapy, immunotherapy |
| Locations | 1 site (Guangzhou, Guangdong) |
| Trial ID | NCT07501351 on ClinicalTrials.gov |
What this trial studies
This phase 2 interventional trial at Sun Yat-sen University Cancer Center compares two second-line strategies for unresectable hepatocellular carcinoma after progression on first-line bevacizumab plus sintilimab: intensified therapy by adding lenvatinib versus conversion therapy using regorafenib combined with a PD-1 inhibitor. Eligible adults (18–75) must have measurable disease, Child-Pugh A/B liver function, ECOG 0–2, and documented progression after at least two cycles of the prior regimen. Participants will receive one of the two combination regimens and be followed with imaging per mRECIST/RECIST v1.1 and routine safety monitoring to compare response, disease control, and adverse events. Findings will provide exploratory comparative data to help guide selection of second-line options and inform larger confirmatory studies.
Who should consider this trial
Good fit: Adults aged 18–75 with unresectable, measurable hepatocellular carcinoma who progressed after at least two cycles of bevacizumab plus sintilimab, with Child‑Pugh A/B liver function and ECOG performance status 0–2, and who can provide informed consent.
Not a fit: Patients with poor liver function (Child‑Pugh C), ECOG >2, significant uncontrolled comorbidities, or prior severe intolerance to lenvatinib, regorafenib, or PD‑1 inhibitors are unlikely to benefit or be eligible.
Why it matters
Potential benefit: If successful, this could identify a better second-line approach that prolongs disease control and delays progression for patients with advanced HCC after first-line immunotherapy failure.
How similar studies have performed: Similar sequencing and combination approaches have shown promising activity in early-phase and observational studies, but direct randomized head-to-head comparisons are scarce.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
Guangzhou, Guangdong
- Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.