NCT07062055 | RECRUITING | Hepatocellular Carcinoma

Detailed Description:

Hepatocellular carcinoma (HCC) remains a major clinical challenge, primarily due to its frequent diagnosis at advanced stages and the limited proportion of patients eligible for curative surgical interventions. For individuals with advanced or unresectable disease, current treatment options include targeted therapy, immunotherapy, and radiotherapy. Although these modalities have led to incremental improvements in survival outcomes, the overall prognosis remains unsatisfactory, with only modest gains in progression-free survival (PFS) and overall survival (OS). Among systemic therapies, multi-targeted tyrosine kinase inhibitors (TKIs) such as sorafenib and lenvatinib have been widely adopted as first-line treatments. However, their clinical benefits are limited by low objective response rates (ORR), significant adverse events, and the eventual emergence of drug resistance. In light of these limitations, anti-angiogenic agents such as bevacizumab have emerged as promising alternatives. Bevacizumab not only inhibits tumor angiogenesis but also modulates the tumor microenvironment to enhance antitumor immune responses, offering a potential synergistic effect when combined with immune checkpoint inhibitors (ICIs). QL1706 is a novel bispecific antibody targeting both programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), designed to enhance T cell-mediated antitumor immunity through dual immune checkpoint blockade. Compared to conventional monoclonal antibodies, this dual-targeting strategy may offer improved antitumor efficacy without a proportional increase in immune-related toxicity. Preliminary clinical studies across multiple tumor types have demonstrated a favorable safety and efficacy profile, supporting its potential for broader oncologic application. Moreover, emerging preclinical and early-phase clinical data suggest that the combination of QL1706 and bevacizumab may have particular therapeutic synergy in HCC. Stereotactic body radiotherapy (SBRT) is a highly precise radiation technique capable of delivering ablative doses to tumor lesions while sparing surrounding healthy tissue. In patients with HCC who are ineligible for surgical resection, SBRT has shown promising outcomes in terms of local tumor control and overall survival. Beyond its cytotoxic properties, SBRT may enhance tumor immunogenicity by promoting antigen release and modulating the tumor microenvironment, thereby potentiating the effects of immunotherapy. This prospective, multicenter, single-arm Phase II clinical trial is designed to evaluate the efficacy and safety of a combination regimen comprising bevacizumab, QL1706, and SBRT in patients with Barcelona Clinic Liver Cancer (BCLC) stage C HCC with portal vein tumor thrombus (PVTT) or extrahepatic oligometastatic disease. The primary endpoint is PFS. Secondary endpoints include OS, ORR, disease control rate (DCR), duration of response (DoR), quality of life (QoL), and safety, as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Exploratory analyses will investigate immunologic responses and biomarker dynamics, including programmed death-ligand 1 (PD-L1) expression, immune cell infiltration (e.g., CD8⁺T cells, natural killer cells), and vascular endothelial growth factor (VEGF)-related alterations within the tumor microenvironment. Patient-reported outcomes, including health-related quality of life, will be assessed using validated instruments such as the EORTC QLQ-C30 questionnaire. ligible patients are required to provide written informed consent and must meet all inclusion criteria as confirmed by imaging and pathological evaluation. The treatment regimen consists of bevacizumab, QL1706, and SBRT. SBRT will be delivered to the intrahepatic primary tumor, PVTT, and any identified extrahepatic oligometastatic lesions. This combination strategy maximizes antitumor efficacy by integrating three complementary mechanisms of action: anti-angiogenesis, immune activation, and localized tumor ablation. Through comprehensive clinical, radiologic, and biomarker-based assessments, this trial aims to determine whether such a multimodal therapeutic approach can provide meaningful clinical benefit for patients with BCLC stage C HCC complicated by PVTT or extrahepatic oligometastatic disease.