World-first Phase Ib trial evaluates carbon-ion radiotherapy combined with immunotherapy for advanced hepatocellular carcinoma with vascular invasion

Chiba University Hospital and QST Hospital of the National Institutes for Quantum Science and Technology announced that they have conducted the world’s first investigator-initiated Phase Ib clinical trial evaluating the safety and efficacy of carbon-ion radiotherapy combined with immunotherapy for advanced hepatocellular carcinoma with macrovascular invasion, meaning cancer invading blood vessels. The trial was carried out with support from the Clinical Research Center at Chiba University Hospital, an Academic Research Organization (ARO). The findings were published in the international hepatology journal JHEP Reports on March 28, 2026. Advanced hepatocellular carcinoma with vascular invasion has an extremely poor prognosis, and existing drug therapies alone often provide insufficient survival benefit. Improving outcomes requires treatment strategies that preserve liver function while addressing both the primary tumor with vascular invasion and metastatic lesions. The research team therefore conducted an investigator-initiated trial combining carbon-ion radiotherapy, which can treat the primary lesion while reducing the risk of liver function deterioration, with immune checkpoint inhibitor-based immunotherapy, which is expected to improve prognosis compared with conventional anticancer drugs. Key findings include: first, this was the world’s first Phase Ib clinical trial to assess the safety of combining carbon-ion radiotherapy with immune checkpoint inhibitor-based immunotherapy for advanced hepatocellular carcinoma. Second, in 15 participants, immune checkpoint inhibitors were administered first, carbon-ion radiotherapy was performed on or after day seven, and immune checkpoint inhibitors were then administered regularly thereafter; this schedule was confirmed to be feasible and safe. Third, the study showed that combining carbon-ion radiotherapy with potent immunotherapy, an approach previously treated cautiously because of safety concerns, can be performed safely and may support the development of new treatments for advanced hepatocellular carcinoma. The study suggests that this new combination therapy could become a promising option for advanced hepatocellular carcinoma. Based on these results, the two hospitals are currently conducting another investigator-initiated clinical trial in patients with large hepatocellular carcinoma. If established, this treatment may improve the prognosis of hepatocellular carcinoma, a disease that is difficult to cure and prone to recurrence. The paper is titled “MVI-targeted Carbon-ion Radiotherapy Combined with Immunotherapy for Advanced Hepatocellular Carcinoma: Phase Ib DEPARTURE Trial” and was published in JHEP Reports. DOI: https://doi.org/10.1016/j.jhepr.2026.101765. Major funding sources include AstraZeneca K.K., Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, and the Japan Cancer Society Relay For Life Japan “Project Mirai” research grant. The jRCT clinical trial registration number is jRCT2031210046.