NCT07514455

Regorafenib After Treatment Failure of First Line Immune Checkpoint Inhibitor Treatment in Advanced Hepatocellular Carcinoma Patients

Regorafenib After Failure of First-Line Immune Checkpoint Inhibitor-Based Combination Therapy in Child-Pugh B Patients With HCC: A Phase 2 RECOMEND Trial

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Ju Hyun Shim · Academic / Other
• Sex: All
• Age: 19 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Immune checkpoint inhibitor (ICI)-based regimens (atezolizumab+bevacizumab, durvalumab+tremelimumab, nivolumab+ipilimumab) are now a first-line standard for advanced hepatocellular carcinoma (HCC). For Child-Pugh (CP) A patients, regorafenib, cabozantinib, and ramucirumab are approved second-line agents, but there is no approved second-line systemic therapy for CP-B. In CP-B historical controls treated with best supportive care, median progression free survival (PFS) was \~1.4 months in a REACH trial subgroup analysis and \~1.9 months in a CELESTIAL trial subgroup analysis. Regorafenib demonstrated benefit as a post-sorafenib second-line therapy in CP-A patients in the RESORCE trial, but prospective evidence in CP-B is lacking. A multicenter retrospective study of CP-B patients receiving second-line regorafenib after sorafenib reported a median PFS of 1.8 months, and prospective data after ICI-based first-line therapy are not available. This study will evaluate the efficacy and safety of regorafenib as second-line therapy in CP-B patients with disease progression after first-line ICI-based treatment. The primary objective is to demonstrate superiority over historical controls, with PFS as the primary endpoint. After written informed consent, all participants will receive regorafenib. Regorafenib will be administered at 120 mg orally once daily at the same time each day, after a meal with water, for 3 consecutive weeks followed by 1 week off (4-week cycle). Treatment must start within 3 days after screening and will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination, whichever occurs first. After treatment discontinuation, patients will be followed every 12 week (+/-7 days) for survival status and subsequent anticancer therapies, and survival follow-up will continue for at least 12 months after enrollment of the last participant.

Conditions

• Carcinoma, Hepatocellular
• Hepatic Insufficien
• Disease Progression
• Treatment Failure

Interventions

Type	Name	Description
DRUG	Regorafenib (BAY 73-4506)	Oral regorafenib 120 mg once daily, taken at the same time each day after a meal with water. The study drug is administered on a 28-day cycle, consisting of 3 consecutive weeks of daily dosing followed by 1 week off. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.

Timeline

• Start date: 2026-03-15
• Primary completion: 2028-05-31
• Completion: 2028-06-30
• First posted: 2026-04-07
• Last updated: 2026-04-07

Locations

1 site across 1 country: South Korea