NCT07151326

Cabozantinib for Progressive HCC Post-first-line Immuno-oncologic Combination Therapy

A Phase II, Single-arm, Multi-center Trial of Cabozantinib for Progressive Hepatocellular Carcinoma (HCC) Post-first-line Immuno-oncologic Combination Therapy (CAPIO Study)

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: National Health Research Institutes, Taiwan · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

1. To investigate the efficacy and safety of cabozantinib in patients with progressive HCC after ICI-based combination treatment. 2. To explore potential tissue and peripheral blood biomarkers associated with clinical benefits of cabozantinib, and resistance mechanisms of prior ICI and cabozantinib.

Detailed description

Immune checkpoint inhibitor (ICI)-based combination therapy, such as atezolizumab-bevacizumab or tremelimumab-durvalumab, has become the current standard first-line treatment for advanced hepatocellular carcinoma (HCC). However, there is no approved second-line treatment yet following progression on these ICI-based combination therapies. Multikinase inhibitors (MKIs), such as lenvatinib, sorafenib, cabozantinib, and regorafenib, are often recommended by established guidelines, expert consensus, and retrospective studies. However, this approach lacks robust evidence from prospective studies or reliable biomarkers for patient selection. Cabozantinib, a MKI targeting vascular endothelial growth factor receptor (VEGFR), MET, and the TAM family of kinases (TYRO3, AXL, and MER), is one of the standard post-sorafenib treatments for advanced HCC. It has shown comparable effectiveness to sorafenib in the first-line setting. The safety profile of cabozantinib is well established and manageable. Furthermore, cabozantinib offers several advantages that make it a rational treatment option after ICI failure: 1. Potent VEGFR inhibition: Cabozantinib effectively inhibits angiogenesis, which is essential for tumor growth. 2. Additional AXL inhibition: Cabozantinib targets AXL, which is a key mediator of tumor progression and ICI resistance across different cancer types. 3. Clinical evidence: A recent phase II trial demonstrated that around 30% of patients receiving cabozantinib after progression with ICIs remained progression-free at 6 months, despite an objective response rate of 6%. This underscores the need for biomarkers to identify patients who are more likely to benefit from cabozantinib after ICI failure. In this trial, the investigators aim to investigate the efficacy and safety of cabozantinib in HCC patients who have progressed on first-line ICI-based combination. Additionally, the investigators will explore tumor tissue and peripheral blood biomarkers for clinical benefits of cabozantinib, and resistance mechanisms of prior ICI and current cabozantinib.

Conditions

• Hepatocellular Carcinoma (HCC)

Interventions

Type	Name	Description
DRUG	Cabozantinib	All patients will be treated with cabozantinib at 60 mg once daily.

Timeline

• Start date: 2025-09-01
• Primary completion: 2028-06-01
• Completion: 2028-06-01
• First posted: 2025-09-03
• Last updated: 2025-09-03

Locations

9 sites across 1 country: Taiwan