Regorafenib Plus Tislelizumab as First-line Systemic Therapy for Patients With Advanced Hepatocellular Carcinoma

Advanced Hepatocellular Carcinoma Clinical Trial

Official title: Regorafenib Plus Tislelizumab as First-line Systemic Therapy for Patients With Advanced Hepatocellular Carcinoma (HCC)

Status Recruiting

Clinical Trial Summary

Combination of anti-angiogenic molecular targeted therapy and anti- programmed cell death -1 immune checkpoint inhibitor (ICI) therapy has shown promising antitumor activity in multiple cancer types, including patients with advanced hepatocellular carcinoma (HCC). The safety profile and optimal dosage of targeted therapy should be carefully evaluated by clinical trials. Regorafenib is one of the standard second-line systemic therapy for advanced HCC. The present study will test the safety and efficacy of combination of regorafenib and tislelizumab, an anti-programmed cell death-1 ICI. The investigator(s) thus hypothesized that combination of tislelizumab and regorafenib is a tolerable regimen and may improve treatment efficacy for patients with advanced HCC. The present study will explore safety and efficacy of the combination of tislelizumab plus regorafenib as first-line therapy for advanced HCC.

Clinical Trial Description

Combination of ICI with anti-angiogenic therapy has been most extensively studies in patients with renal cell carcinoma, for whom both ICI and anti-angiogenic therapy have proven anticancer activity as single-agent therapy. Objective response rate of 30-60% was observed, far exceeding the response rate of single-agent therapy (around 20%). Results from several early-phase trials of this type of combination also support the potential anti-tumor synergy between ICI and anti-angiogenic therapy (multi-kinase inhibitors or monoclonal antibody targeting the vascular endothelial growth factor signaling pathway) in advanced HCC. Further studies should focus on identifying the optimal targeted agent and its biologically effective dosage to achieve the best therapeutic window for the treatment of HCC.

Current evidence indicated the following:

1. Combination of ICI and anti-angiogenic therapy in advanced HCC may have better anti-tumor efficacy compared with single-agent therapy;

2. The immune modulatory effects of the multi-kinase inhibitors may be achieved at dosage lower than recommended for single-agent therapy in the clinic; using this lower dosage when combined with ICI may lower the treatment-related adverse events.

3. Objective response of 40% to 50% was recently reported in a phase 1 study of regorafenib plus nivolumab for patients with advanced gastric or colorectal cancer was reported recently (Fukuoka S, et al. American Society Of Clinical Oncology 2019, abstract#2522). Grade 3 or greater treatment-related adverse events were found in 27% of subjects who received regorafenib 80 mg per day and in 44% of patients who received regorafenib 120 mg per day. Therefore, regorafenib 80 mg/day was defined as the optimal dosage in combination with nivolumab. ;

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular

• NCT number: NCT04183088
• Study type: Interventional
• Source: National Taiwan University Hospital
• Contact: Chiun HSU, MD, PhD
• Phone: +886-2312-3456
• Email: chsu1967@ntu.edu.tw,hsuchiun@gmail.com
• Status: Recruiting
• Phase: Phase 2
• Start date: December 16, 2020
• Completion date: March 1, 2025