NCT05134532

Regorafenib After Progression on Atezolizumab Plus Bevacizumab in Advanced HCC

Phase II Trial of Regorafenib in Patients With Unresectable Hepatocellular Carcinoma After Progression on First Line Atezolizumab Plus Bevacizumab (REGONEXT Trial)

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: CHA University · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

Summary

To investigate efficacy and toxicity of regorafenib after treatment with atezolizumab and bevacizumab combination

Detailed description

* There is preclinical and clinical data on synergistic activity of angiogenesis inhibitors and anti-programmed death-1 (anti-PD-1) targeted therapy. Targeting VEGFR decreased T-regulatory cells and Myeloid-derived suppressor Cells. In addition, VEGF-A produced in the tumor microenvironment enhanced expression of PD-1 involved in CD8 T cell exhaustion8. The combination of targeted therapy and immune-checkpoint inhibitors (ICIs), either in a parallel or sequential manner, could theoretically lead to enhanced anti-tumor responses, reflected in durable responses and prolonged survival. However, there have been lack of clinical data of targeted agents who developed progressive disease with ICIs. * In previous phase I study, pharmacodynamics indicated a sustained occupancy of \> 70% of PD-1 molecules on circulating T-cells ≥ 2 months following infusion. Based on these findings, ICI use may retain the prolonged effect even after discontinuation. There was a case report of a sorafenib-refractory patient experiencing progressive disease during ICI combination treatment with the anti-PD-1 antibody and the anti-GITR antibody within phase I trial followed by a prolonged tumor response during third-line regorafenib monotherapy. * In patients with advanced HCC, anti-VEGF monoclonal antibodies, multi-kinase inhibitor (sorafenib, regorafenib, cabozantinib and lenvatinib) and ICIs are available treatment options, however, treatment sequencing and combination strategy are challenging. * Atezolizumab plus bevacizumab demonstrated survival benefit and established as a new first-line therapy, hence it is clinically important to study the efficacy and toxicity of regorafenib after treatment with ICIs or ICI combination.

Conditions

• Hepatocellular Carcinoma

Interventions

Type	Name	Description
DRUG	regorafenib	Regorafenib 160 mg orally every day for 3 weeks of every 4-week cycle (i.e. 3 weeks on, 1 week off) plus best supportive care

Timeline

• Start date: 2021-12-24
• Primary completion: 2024-10-30
• Completion: 2024-10-30
• First posted: 2021-11-26
• Last updated: 2023-04-26

Locations

2 sites across 1 country: South Korea