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Completed

NCT Number: NCT07537985

Efficacy and Safety Comparison Between PD-1 Inhibitor Combined With Lenvatinib or With Regorafenib For UHCC After Failure of First-line Treatment

There is no definitive evidence regarding the therapeutic efficacy of PD-1 inhibitors combined with tyrosine kinase inhibitors (TKIs) after disease progression following first-line treatment with bevacizumab plus sintilimab for unresectable hepatocellular carcinoma (HCC). There is insufficient evidence to support which TKI should be combined with PD-1 inhibitors as the optimal second-line treatment option after first-line therapy failure. Data on the application of lenvatinib as a second-line treatment are limited, whereas the efficacy and safety of regorafenib combined with PD-1 inhibitors have been preliminarily validated [9]. Therefore, this study aims to compare the efficacy and safety of PD-1 inhibitors combined with either lenvatinib or regorafenib after disease progression following first-line bevacizumab plus sintilimab treatment for unresectable HCC, providing evidence-based guidance for the selection of second-line treatment regimens in clinical practice.

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Key information

Conditions

Hepatocellulcar Carcinoma

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510000, China

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diagnosed with hepatocellular carcinoma (HCC) based on histological or clinical diagnostic criteria;
  • Classified as unresectable HCC following multidisciplinary assessment;
  • Presence of at least one tumor lesion measurable according to EASL criteria;
  • Patients aged ≥18 years and ≤75 years receiving first-line treatment;
  • Child-Pugh liver function class A/B, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score 0-2;
  • 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);
  • Received ≥2 cycles of post-progression treatment with bevacizumab plus sintilimab, lenvatinib, or regorafenib combined with PD-1 inhibitors;
  • 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;
  • Availability of complete baseline data, treatment records, and follow-up data (including imaging assessments, laboratory tests, and clinical documentation).

Exclusion criteria

  • Life expectancy ≤2 months;
  • Presence of intrahepatic cholangiocarcinoma, mixed hepatocellular-cholangiocarcinoma, or other non-HCC malignancies;
  • Active concurrent malignancy or severe comorbid conditions;
  • First-line treatment with other anticancer therapies (chemotherapy, radiotherapy, surgery, or other interventions) concurrently;
  • Known hypersensitivity to study drugs.

Treatment and study plan

Lenvatinib

Drug

Lenvatinib, for weight ≤60 kg, 8 mg/d, po, qd; for weight >60 kg, 12 mg/d, po, qd.

regorafenib

Drug

Regorafenib, 160mg/d, po, qd.

PD-1 inhibitor

Drug

PD-1 inhibitor (Sintilimab, Camrelizumab, Tislelizumab, Toripalimab, Pembrolizumab, Nivolumab), 200mg/dose, iv drip, q3w.

Primary outcomes

  1. Overall Survival (OS)

    Time frame: 6 months

    OS is the length of time from the date of randomization until death from any cause.

  2. Progression Free Survival (PFS)

    Time frame: 6 months

    PFS is defined as the time from the date of randomization to the date of the first objectively documented tumor progression or death due to any cause.

Secondary outcomes

  1. Objective Response Rate (ORR)

    Time frame: 6 months

    ORR, as determined based on tumor response according to RECIST 1.1, is defined as the proportion of all randomized subjects whose best overall response (BOR) is either a CR or PR.

  2. Adverse Events

    Time frame: 30 days

    ORR, as determined based on tumor response according to RECIST 1.1, is defined as the proportion of all randomized subjects whose best overall response (BOR) is either a CR or PR.

Sponsors and collaborators

Lead sponsor

Sun Yat-sen University

Other

Registry information

Official study title

The Efficacy and Safety of PD-1 Inhibitor Combined With Lenvatinib or With Regorafenib For Advanced Hepatocellular Carcinoma After Failure of First-line Bevacizumab Plus Sintilimab: A Retrospective Study

Important dates

Study start
2020
Primary completion
2025
Study completion
2025
First posted
Apr 17, 2026
Registry last updated
Apr 17, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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