An integrated Phase II/III randomized study comparing durvalumab and tremelimumab ± Hepatic ArteriaL infusion chemotherapy with GEMOX in hepatocellular Carcinoma with high tumor burdEn - ALICE (PRODIGE89 - UCGI44 - ALICE).

Patients with advanced hepatocellular carcinoma and high tumour burden (Vp4 PVTT, Vp3 PVTT with bilateral involvement, >50% liver involvement) have poor outcomes and are under-represented in major hepatocellular carcinoma trials (1,2). HAIC has been widely studied in Asian population, with positive results especially in patients with high tumour burden but is not validated in Western population. The ALICE study is a multicentre, French, open-label, randomised integrated phase II/III trial designed to evaluate the safety and efficacy of GEMOX (gemcitabine and oxaliplatin)-based HAIC in combination with durvalumab and tremelimumab, versus durvalumab and tremelimumab alone in this population. A total of 90 and 196 patients will be enrolled in the phase II and phase III components, respectively, and randomised 1:1 between the two treatment arms. Primary endpoints are objective response rate (RECIST 1.1) for phase II and overall survival for phase III. A safety run-in with independent Data and Safety Monitoring Board review is planned during phase II to assess tolerance of the combination. Progression to phase III will depend on a predefined futility rule based on the ORR observed in the experimental arm.