Proton Radiotherapy Plus Tremelimumab/Durvalumab for BCLC Stage B and C HCC

Tremelimumab plus durvalumab (STRIDE regimen) is an approved first-line therapy for unresectable hepatocellular carcinoma (HCC), yet it shows limited efficacy with an ORR of only 20.1%. Proton radiotherapy (RT), known for its precision and tissue-sparing advantages, has demonstrated improved survival outcomes and reduced toxicity compared to X-ray RT. Retrospective data suggest that combining proton RT with immune checkpoint inhibitors yields a promising ORR of 61.5%. Preclinical studies further support enhanced antitumor immunity when RT is combined with PD-L1 and CTLA-4 blockade. This phase II, single-arm clinical trial aims to evaluate the safety, efficacy, and immunologic effects of combining proton RT with tremelimumab and durvalumab in patients with unresectable HCC.

NCT Number	NCT06999694
Lead Sponsor	Chang Gung Memorial Hospital
Conditions	HCC - Hepatocellular Carcinoma, Durvalumab, Tremelimumab, Proton Radiotherapy
Enrollment	45 participants
Start Date	2025-05-22
Primary Completion	2030-05-31 (estimated)
Study Completion	2033-05-31 (estimated)
Updated on ClinicalTrials.gov	2025-09-10