Aim: To evaluate the safety, pharmacokinetics and antitumor activity of OPB-31121, a signal transducer and activator of transcription-3 inhibitor, in patients with advanced hepatocellular carcinoma (HCC).
Methods: HCC patients of Child-Pugh A or B who progressed on, or were intolerant to, sorafenib were eligible for this phase 1 trial. We used a standard 3 + 3 dose-escalation design with a 28-day cycle at dose levels of 50, 100, 200 and 400 mg/day. Tumor responses were assessed using the modified Response Evaluation Criteria in Solid Tumors.
Results: Twenty-four patients were enrolled, of whom 23 received OPB-31121 (20 males; median age, 65 years). The most common adverse drug reactions were nausea (87.0%), vomiting (82.6%), diarrhea (69.6%), fatigue/malaise (52.2%), anorexia (47.8%) and peripheral sensory neuropathy (26.1%). The recommended dose for OPB-31121 was determined to be 200 mg. Six patients had stable disease for 8 weeks or more, resulting in disease control rates of 25.0-42.9%. In the 200-mg dose cohort, three of seven patients had stable disease and a median time to progression of 61.0 days. The maximum concentration and area under the plasma concentration-time curve of OPB-31121 were dose proportional.
Conclusion: OPB-31121 demonstrated insufficient antitumor activity for HCC. Furthermore, peripheral nervous system-related toxicities may negatively affect long-term administration of OPB-31121. Therefore, it was deemed difficult to continue the clinical development of OPB-31121 for treating advanced HCC and further investigation is expected in the agent with favorable profile in this category.
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Institute of Oncology Research (IOR), Via Vela 6, 6500 Bellinzona, Switzerland; Oncology Institute of Southern Switzerland (IOSI), Via Vela 6, 6500 Bellinzona, Switzerland. Electronic address:
STAT3 is a key element in many oncogenic pathways and, like other transcription factors, is an attractive target for development of novel anticancer drugs. However, interfering with STAT3 functions has been a difficult task and very few small molecule inhibitors have made their way to the clinic. OPB-31121, an anticancer compound currently in clinical trials, has been reported to affect STAT3 signaling, although its mechanism of action has not been unequivocally demonstrated.
View Article and Find Full Text PDFPhase I Study of OPB-31121, an Oral STAT3 Inhibitor, in Patients with Advanced Solid Tumors.
Cancer Res Treat
October 2015
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Purpose: OPB-31121 is an oral STAT3 inhibitor with a good preclinical antitumor activity. This phase I dose-escalation study of OPB-31121 was conducted to determine maximum-tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor efficacy in patients with advanced solid tumors.
Materials And Methods: Patients received OPB-31121 once daily for 28 days of each cycle followed by 2 weeks rest.
Aim: To evaluate the safety, pharmacokinetics and antitumor activity of OPB-31121, a signal transducer and activator of transcription-3 inhibitor, in patients with advanced hepatocellular carcinoma (HCC).
Methods: HCC patients of Child-Pugh A or B who progressed on, or were intolerant to, sorafenib were eligible for this phase 1 trial. We used a standard 3 + 3 dose-escalation design with a 28-day cycle at dose levels of 50, 100, 200 and 400 mg/day.
Phase 1, open-label, dose-escalation, and pharmacokinetic study of STAT3 inhibitor OPB-31121 in subjects with advanced solid tumors.
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Sarah Cannon Research Institute/Tennessee Oncology, PLLC, 3322 West End Avenue, Suite 900, Nashville, TN, 37203, USA,
Purpose: To determine the maximum tolerated dose (MTD) and biologic activity of OPB-31121, an oral inhibitor of STAT3, administered twice daily (BID) to subjects with advanced solid tumors.
Methods: Subjects received escalating doses of OPB-31121 BID for the first 21 days of each 28-day cycle in a standard 3 + 3 design. Dose-limiting toxicities (DLTs), safety, pharmacokinetics, and antitumor activity were assessed.
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