Icaritin early phase Trial: With poor prognosis and limitedtreatment options for advanced hepatocellular carcinoma (HCC),development ofnovel therapeutic agents is urgently needed. This single-arm phase I studysought to assess thesafety and preliminary efficacy of icaritin in human as apotential oral immunotherapy in addition to the immune-checkpoint inhibitors.

Keyfindings of this icaritin study include: 1) Nodrug-related adverse events≥Grade 3 were observed in all 20 enrolled HCC patients. 2) Among the15evaluable patients, 7 (46.7%) achieved clinical benefit, representing onepartial response (PR, 6.7%) and 6 stable disease (SD, 40%). The median TTP was141 days. Durable survival was observed in PR/SD patients with a median OS of488 days (range: 72-773). TTP was significantly associated with the dynamicchanges of peripheral neutrophils (p= 0.0067) and lymphocytes (p= 0.0337).Icaritin treatment induced changes in immune biomarkers-and immune-suppressivemyeloid cells were observed.

Summary: Icaritin demonstrated safety profiles and preliminary durablesurvival benefits in advanced HCC patients, which were correlated with itsimmune-modulation activities and immune biomarkers. These results suggestedthepotential of icaritin as a novel oral immunotherapy for advanced HCC inaddition to antibody-based PD-1/PD-L1blockade therapies.