ESTRO 2024 - Abstract Book

S2129

Clinical - Upper GI

ESTRO 2024

95

Mini-Oral

Phase Ib trial of Durvalumab plus tremelimumab with particle therapy for advanced HCC: DEPARTURE

Hirokazu Makishima 1,2 , Sadahisa Ogasawara 3 , Keisuke Koroki 3 , Masaru Wakatsuki 2 , Asahi Takahashi 4 , Hiroaki Kanzaki 3 , Kazufumi Kobayashi 3 , Masanori Inoue 3 , Soichiro Kiyono 3 , Masato Nakamura 3 , Naoya Kanogawa 3 , Takayuki Kondo 3 , Shingo Nakamoto 3 , Yuki Shiko 3 , Yoshihito Ozawa 4 , Yosuke Inaba 4 , Tomoya Kurokawa 4 , Hideki Hanaoka 4 , Shigeru Yamada 2 , Naoya Kato 3 1 University of Tsukuba, Department of Radiation Oncology, Tsukuba, Japan. 2 National Institutes for Quantum Science and Technology, QST Hospital, Chiba, Japan. 3 Chiba University, Department of Gastroenterology, Chiba, Japan. 4 Chiba University Hospital, Clinical Research Center, Chiba, Japan

Purpose/Objective:

Hepatocellular carcinoma (HCC) has a unique character and even when extrahepatic lesions are observed, intrahepatic lesions tend to be the prognosis-defining lesion, especially when macrovascular invasion (MVI) is observed. Recent breakthroughs realised with immuno-checkpoint inhibitors (ICI) have improved the prognosis of Barcelona Clinic Liver Cancer Stage C HCC patients but still fall short in cases with MVI and the development of a revolutionary therapeutic approach is required. Particle therapy, both proton beam therapy and carbon-ion radiotherapy (C-ion RT) has been reported to provide good local control in patients with HCC while maintaining liver function, including those with MVI. This is realised by the exceptional dose distribution of particle therapy, delivering high doses to the tumour while sparing the particularly radiosensitive normal liver tissue. Radiotherapy is also known to have both immunostimulant and immunosuppressant effects and both are stronger with higher doses, potentially making particle therapy a good match with ICI combination therapy. Based on this, we hypothesized that particle therapy in combination with ICI could provide a survival benefit in advanced HCC patients. The DEPARTURE trial aims to evaluate whether treatment with durvalumab, alone or in combination with tremelimumab, plus particle therapy is safe, and explore the possibility of being a synergistically effective treatment for advanced HCC with MVI. This is a Phase Ib, multicentre, open-label, single-arm, investigator-initiated clinical trial testing durvalumab monotherapy in combination with particle therapy (Cohort A) and that of durvalumab plus tremelimumab in combination with particle therapy (Cohort B) in advanced HCC patients with MVI who have preserved liver function of Child – Pugh A. Both cohorts began with patients resistant to standard treatments. After safety confirmation, the study expanded to systemic therapy-naïve patients, totalling 15. Cohort A receives 1500 mg of durvalumab every four weeks. Cohort B receives the same 1500 mg of durvalumab every four weeks plus an additional 300 mg of tremelimumab on day 1 of the first cycle. As particle therapy, carbon-ion radiotherapy (C-ion RT) begins after day 8 following the initial drug administration. The relative biological effectiveness weighted dose is set at 60 Gy in four fractions over one week, targeting one representative intrahepatic nodule with MVI. The primary endpoint is adverse event rates, including dose-limiting toxicity (DLT), with secondary endpoints on progression-free survival (PFS) and overall survival (OS) (jRCT2031210046). Material/Methods: