Reference Detail

Ref Type

Journal Article

PMID

(25715763)

Authors

Oh DY, Lee SH, Han SW, Kim MJ, Kim TM, Kim TY, Heo DS, Yuasa M, Yanagihara Y, Bang YJ

Title

Phase I Study of OPB-31121, an Oral STAT3 Inhibitor, in Patients with Advanced Solid Tumors.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cancer research and treatment : official journal of Korean Cancer Association	47	4	2015 Oct	607-15	Cancer Res Treat

URL

Abstract Text

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.Patients received OPB-31121 once daily for 28 days of each cycle followed by 2 weeks rest. A standard 3+3 design was used for dose-escalation. Safety and response were evaluated by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) ver. 3.0 and Response Evaluation Criteria in Solid Tumor (RECIST) ver. 1.0, respectively.Twenty-five patients were treated with OPB-31121 at five dose levels: 100 mg (n=4), 200 mg (n=3), 400 mg (n=3), 600 mg (n=7), and 800 mg (n=8). Seven patients discontinued treatment during cycle 1 for various reasons other than study drug-related adverse events. Among 18 patients who were evaluable for dose-limiting toxicity (DLT), three DLTs were observed: one DLT (grade 3 vomiting) at 600 mg and two DLTs (grade 3 vomiting, grade 3 diarrhea) at 800 mg. The MTD was determined as 800 mg/day. Common adverse events were gastrointestinal adverse event including nausea (84%), vomiting (80%), and diarrhea (72%). Pharmacokinetics did not demonstrate dose-proportionality of OPB-31121. Eight patients had stable disease and 10 patients had disease progression. Two patients (1 colon cancer, 1 rectal cancer) showed tumor shrinkage. One gastric cancer patient continued treatment up to cycle 13 before disease progression.This study demonstrates feasibility of STAT3 inhibition in patients with advanced solid tumor. OPB-31121, at the MTD of 800 mg/day, was safe and relatively well tolerated, and has a preliminary antitumor activity.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
OPB-31121	OPB-31121	0	0

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
OPB-31121		OPB 31121	STAT3 Inhibitor 26	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