Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of (South), Korea
Changhoon Yoo , Jihoon Kang , Kyu-Pyo Kim , Ho Yeong Lim , Jee Hyun Kim , Myung Ah Lee , Tae-You Kim , Baek-Yeol Ryoo
Background: The signal transducer and activator of transcription 3 (STAT3) signaling pathway might be a promising therapeutic target for hepatocellular carcinoma (HCC). Methods: This study was a multicenter, open-label, non-comparative, dose escalating phase I study of OPB-111077, an oral STAT3 inhibitor, in patients with advanced HCC who failed on sorafenib. Continuous dosing (daily administration: 50 mg to 400 mg) and intermittent dosing (4-days on/3-days off administration: 300 mg to 900 mg) regimens were evaluated and the dose-limiting toxicities (DLTs), maximal tolerated dose (MTD), and recommended dose (RD) were the primary endpoints. Results: A total of 33 patients (19 for continuous dosing and 14 for intermittent dosing) were enrolled. One patient experienced a DLT with grade 3 dizziness, but the MTD was identified in neither the continuous nor the intermittent dosing cohorts. The RDs were determined to be 250 mg for the continuous dosing regimen and 600 mg for the intermittent dosing regimen. There was no treatment-related death; 6 patients (18%) had grade 3-4 toxicities including thrombocytopenia (6%), fatigue (3%), and dizziness (3%). No patients achieved complete or partial responses and the median progression-free survival was 1.4 months (95% confidence interval, 0.8-2.8). Conclusions: OPB-11107 was well tolerated in patients with advanced HCC after sorafenib failure, but only showed limited preliminary efficacy outcomes. Further investigation of the role of the STAT3 signaling pathway in HCC and the development of biomarkers for STAT3 inhibitors are warranted. Clinical trial information: NCT01942083
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