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|Ref Type||Journal Article|
|Authors||Okusaka T, Ueno H, Ikeda M, Mitsunaga S, Ozaka M, Ishii H, Yokosuka O, Ooka Y, Yoshimoto R, Yanagihara Y, Okita K|
|Title||Phase 1 and pharmacological trial of OPB-31121, a signal transducer and activator of transcription-3 inhibitor, in patients with advanced hepatocellular carcinoma.|
|Journal||Hepatology research : the official journal of the Japan Society of Hepatology|
|Abstract Text||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).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.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.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.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|OPB-31121||OPB 31121||STAT3 Inhibitor 21||OPB-31121 is a small molecule inhibitor of Stat3 that demonstrates antitumor activity (PMID: 23402820, PMID: 25715763, PMID: 25676869, PMID: 24819685).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||hepatocellular carcinoma||no benefit||OPB-31121||Phase I||Actionable||In a Phase I trial, OPB-31121 treatment resulted in only stable disease in 26% (6/23) of patients with advanced hepatocellular carcinoma, and was considered insufficient for clinical efficacy (PMID: 25676869).||25676869|