Regorafenib After Treatment Failure of First Line Immune Checkpoint Inhibitor Treatment in Advanc… (NCT07514455) | Clinical Trial Compass
Not Yet RecruitingPhase 2
Regorafenib After Treatment Failure of First Line Immune Checkpoint Inhibitor Treatment in Advanced Hepatocellular Carcinoma Patients
South Korea20 participantsStarted 2026-03-15
Plain-language 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.
Who can participate
Age range19 Years – 80 Years
SexALL
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Inclusion criteria
✓. Voluntarily signed written informed consent form.
✓. Age ≥19 years at the time of signing the informed consent form.
✓. Histologically or clinically diagnosed hepatocellular carcinoma (HCC) according to the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) guidelines.
✓. Disease progression or treatment discontinuation due to toxicity during first-line immune checkpoint inhibitor-based combination therapy (atezolizumab plus bevacizumab, durvalumab plus tremelimumab, or nivolumab plus ipilimumab).
✓. At least one measurable target lesion according to RECIST v1.1.
✓. Child-Pugh score B (7-8).Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
✓. Adequate hematologic and end-organ function defined by the following laboratory results obtained within 14 days prior to the test (or enrollment):
Exclusion criteria
✕. ALBI (Albumin-Bilirubin) grade 3.
What they're measuring
1
Progression Free Survival
Timeframe: From treatment initiation until the date of first documented progression or death from any cause, whichever comes first, assessed up to 36 months.
. Fibrolamellar carcinoma or sarcomatoid carcinoma.
✕. Prior treatment with regorafenib.
✕. Within 2 weeks since the last administration of an immune checkpoint inhibitor.
✕. Receipt of any other systemic or locoregional therapy after the failure of first-line immune checkpoint inhibitor-based therapy.
✕. History of allogeneic stem cell transplantation or solid organ transplantation.
✕. Active brain metastases or leptomeningeal metastases.
✕. History of malignancy other than hepatocellular carcinoma (HCC) within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year survival rate \> 90%).