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

NCT07537985 | Completed DMC

• 1 other identifier: IM-LENREG
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatocellulcar Carcinoma

Keywords

Bevacizumab; Sintilimab; Lenvatinib; Regorafenib; PD-1; ICIs; second-line treatment

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS)

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

  6 months

• Progression Free Survival (PFS)

  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.

  6 months

Secondary Outcomes (2)

• Objective Response Rate (ORR)

  6 months

• Adverse Events

  30 days

Study Arms (2)

LP Group

EXPERIMENTAL

Lenvatinib, PD-1 Inhibitor

Drug: Lenvatinib; Drug: PD-1 Inhibitor

RP Group

ACTIVE COMPARATOR

Regorafenib, PD-1 Inhibitor

Drug: Regorafenib; Drug: PD-1 Inhibitor

Interventions

Lenvatinib DRUG

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

LP Group

Regorafenib DRUG

Regorafenib, 160mg/d, po, qd.

RP Group

PD-1 Inhibitor DRUG

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

LP Group; RP Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510000, China

Location

MeSH Terms

Interventions

lenvatinib; regorafenib; Immune Checkpoint Inhibitors

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 12, 2026
• First Posted: April 17, 2026
• Study Start: January 1, 2020
• Primary Completion: August 1, 2025
• Study Completion: December 25, 2025
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

CN (1)