NCT06045975

Durvalumab/Tremelimumab in Neoadjuvant and Adjuvant Setting in Patients With HCC Treated by by Percutaneous Ablation Procedure

Durvalumab/Tremelimumab in Neoadjuvant and Adjuvant Setting in Patients With HCC Treated by by Percutaneous Ablation Procedure in Curative Intent: French Multicenter Phase 2 Therapeutic

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

This project is a Phase 2 trial testing the safety and efficacy of treatment with Durvalumab/Tremelimumab in neoadjuvant and Durvalumab in adjuvant setting in patients with BCLC A HCC treated by by percutaneous ablation (PA) procedure in a curative intent. DUMELEP is a Multicentre, Phase 2 trial Eligible patients will receive consecutively: 1. 1 Durvalumab 1500 mg/Tremelimumab 300 mg infusion in a neoadjuvant setting 2. percutaneous ablation procedure in a curative attempt at Day 30 3. 11 monthly Durvalumab 1500 mg infusions. 4. Classical follow-up during an additional year (every 3 months)

Detailed description

Immunotherapy is currently the gold standard for first-line treatment of advanced HCC based of the combination of check-point inhibitors (CPI). The first approved regimen is based on the association of atezolizumab and bevacizumab, an antiangiogenic molecule. More recently, the HIMALAYA trial demonstrated the superiority of durvalumab-tremelimumab over sorafenib, establishing a new first-line option.The combination of Immunotherapy and locoregional treatments in earlier HCC stages may reduce relapse rates. Preliminary data from the IMBRAVE 050 trail reports lower rates of recurrence following HCC percutaneous ablation (PA) or resection associated with atezolizumab and bevacizumab in adjuvant setting.PA procedures and most likely electroporation induce T-cell recruitment that may foster immunomodulation. In particular, radiofrequency ablation (RFA) can lead to stimulation of NK cells with a more differentiated and proactivatory phenotypic profile with general increase of functional activities. As compared with RFA, these local changes of IRE induce more robust systemic effects, including both tumorigenic and immunogenic events. Indeed, the preservation of the tumor microvasculature and extracellular matrix within the coagulated zone would favour infiltration by anti tumoral immune cells. These observations are relevant for development of neoadjuvant and adjuvant immunotherapeutic strategies in the setting of HCC treated by percutaneous ablation, and particularly IRE . Neoadjuvant and adjuvant trials using these new molecules must now be cautiously designed based on the rigorous selection of special populations and therapeutic indications based on the following criteria: * Exclusion of early forms of HCC with low probability of recurrence for statistical power issues * Inclusion of patients with HCC treated in "curative intent" by new PA techniques such as electroporation * Selective inclusion of patients treated with PA whose immunomodulatory properties are recognized

Conditions

• HCC - Hepatocellular Carcinoma

Interventions

Type	Name	Description
DRUG	Durvalumab/Tremelimumab in neoadjuvant and Durvalumab in adjuvant setting	* Durvalumab 1500 mg/Tremelimumab 300 mg infusion in a neoadjuvant setting followed by PA procedure at Day 30+/-7 days * 11 monthly Durvalumab 1500 mg infusions.

Timeline

• Start date: 2024-03-28
• Primary completion: 2027-09-28
• Completion: 2028-09-28
• First posted: 2023-09-21
• Last updated: 2025-04-02

Locations

1 site across 1 country: France