Eparlitozoviril as Adjuvant Therapy for Resectable HCC With MVI

Summary

Tumor recurrence is the leading cause of death and a major bottleneck for long-term survival in patients with hepatocellular carcinoma (HCC). Therefore, there is an urgent clinical need for effective postoperative adjuvant therapies to reduce postoperative recurrence and improve long-term survival, especially for HCC patients with high-risk factors. However, no standard adjuvant treatment regimen has been established so far, and domestic and international guidelines have not reached a consensus on relevant recommendations. It is generally recognized that postoperative antiviral therapy with nucleoside analogues and interferon yields definite benefits for patients with HBV- or HCV-related HCC, particularly those in Asian populations. Some interventions have been proven ineffective. For instance, the majority of studies have demonstrated that postoperative chemotherapy fails to bring survival benefits and may even lead to worse prognosis in HCC patients. Besides, multiple treatment modalities including transarterial chemoembolization (TACE), radiotherapy, targeted therapy and immunotherapy are still under investigation.

MVI has been well documented as a strong high-risk factor for postoperative recurrence of HCC. The presence of MVI indicates the capacity of tumor cells for local invasion and distant metastasis. According to the number and location of microscopic tumor foci observed under pathological microscopy, MVI is classified into three grades: (1) M0: No microscopic tumor foci detected; (2) M1: No more than 5 microscopic foci within 1 cm adjacent to the primary tumor; (3) M2: More than 5 microscopic foci or foci located beyond 1 cm from the primary tumor. A retrospective study from Zhongshan Hospital, Fudan University enrolled 661 HCC patients who developed recurrence within 5 years after curative resection, and reported that the rate of MVI positivity was 31.6% among these recurrent cases. Another retrospective study conducted at Eastern Hepatobiliary Surgery Hospital of Shanghai involving 496 HCC patients showed that patients with MVI had significantly lower recurrence-free survival (RFS) and overall survival (OS) compared with those without MVI. A series of studies have been carried out to explore postoperative adjuvant treatments for resectable HCC patients complicated with MVI. A phase III randomized controlled trial conducted by Wei et al. revealed that for patients with single resectable HCC (tumor ≥ 5 cm) combined with MVI, postoperative adjuvant TACE (1 to 2 cycles) achieved a median disease-free survival (DFS) of 17.45 months (95% CI: 11.99-29.14), versus 9.27 months (95% CI: 6.05-13.70) in the active surveillance group (HR=0.70, p=0.020). In addition, Li et al. evaluated the efficacy of postoperative adjuvant FOLFOX-based hepatic arterial infusion chemotherapy (HAIC) in resectable HCC patients with MVI. The results demonstrated that adjuvant HAIC could significantly prolong DFS, with a median DFS of 20.3 months versus 10.0 months (p=0.001). Collectively, active postoperative intervention is clinically meaningful for resectable HCC patients with MVI.

In recent years, tumor immunotherapy represented by immune checkpoint inhibitors, including antibodies against programmed death-1 (PD-1), programmed death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), has gradually become a key therapeutic strategy for malignancies. Tumor cells can inhibit T cell activity and evade immune surveillance by expressing immune checkpoint ligands. Blockade of these immune checkpoints can enhance the proliferation, survival and cytotoxicity of T cells, thereby exerting anti-tumor effects. Anti-PD-1/PD-L1 antibodies have exhibited favorable efficacy in a variety of solid tumors.

Given the high postoperative recurrence risk of resectable HCC with MVI and the lack of consensus on standard adjuvant regimens, as well as the proven efficacy of PD-1 monoclonal antibodies and HAIC in this setting in previous randomized controlled trials, we designed a prospective, single-center, open-label, phase II cohort study. This study aims to preliminarily evaluate the efficacy and safety of eparlitozoviril (dual PD-1/CTLA-4 immunotherapy), compared with active surveillance, in resectable HCC patients with MVI. The findings of this study may provide evidence for the optimization of postoperative adjuvant treatment for HCC.

Conditions

• HCC - Hepatocellular Carcinoma

Interventions

DRUG

eparlitozoviril

Eparlitozoviril: 7.5 mg/kg iv q3w. Treatment duration: up to 6 months, or until disease recurrence, death or intolerable AEs.

OTHER

Control group

Active surveillance, every 3 months, until disease recurrence, death.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-06-12

Primary Completion

2028-06-30

Completion

2029-06-30

Countries

• China

Study Locations