BMC Cancer (Mar 2019)

First-in-class immune-modulating small molecule Icaritin in advanced hepatocellular carcinoma: preliminary results of safety, durable survival and immune biomarkers

  • Ying Fan,
  • Shu Li,
  • Xiaoyan Ding,
  • Jian Yue,
  • Jun Jiang,
  • Hong Zhao,
  • Rui Hao,
  • Weiliang Qiu,
  • Kezhen Liu,
  • Ying Li,
  • Shengdian Wang,
  • Limin Zheng,
  • Bin Ye,
  • Kun Meng,
  • Binghe Xu

DOI
https://doi.org/10.1186/s12885-019-5471-1
Journal volume & issue
Vol. 19, no. 1
pp. 1 – 11

Abstract

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Abstract Background With poor prognosis and limited treatment options for advanced hepatocellular carcinoma (HCC), development of novel therapeutic agents is urgently needed. This single-arm phase I study sought to assess the safety and preliminary efficacy of icaritin in human as a potential oral immunotherapy in addition to the immune-checkpoint inhibitors. Methods Eligible advanced HCC patients with Child-Pugh Class A or B were administered with a fixed oral dose of icaritin at either 600 or 800 mg b.i.d. The primary endpoint was safety, and the secondary endpoints included time-to-progression (TTP), overall survival (OS) and the clinical benefit rate (CBR). Icaritin treatment induced immune biomarkers and immune-modulating activities in myeloid cells were also explored. Results No drug-related adverse events ≥ Grade 3 were observed in all 20 enrolled HCC patients. Among the 15 evaluable patients, 7 (46.7%) achieved clinical benefit, representing one partial response (PR, 6.7%) and 6 stable disease (SD, 40%). The median TTP was 141 days (range: 20-343 days), and the median OS was 192 days (range: 33-1036 days). Durable survival was observed in PR/SD patients with a median OS of 488 days (range: 72-773). TTP was significantly associated with the dynamic changes of peripheral neutrophils (p = 0.0067) and lymphocytes (p = 0.0337). Icaritin treatment induced changes in immune biomarkers-and immune-suppressive myeloid cells were observed. Conclusions Icaritin demonstrated safety profiles and preliminary durable survival benefits in advanced HCC patients, which were correlated with its immune-modulation activities and immune biomarkers. These results suggested the potential of icaritin as a novel oral immunotherapy for advanced HCC in addition to antibody-based PD-1/PD-L1 blockade therapies. Trial registration Clinicaltrial.gov identifier. NCT02496949 (retrospectively registered, July 14, 2015).

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