Related Experiment Video
Updated: Apr 16, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Phase I Study of OPB-31121, an Oral STAT3 Inhibitor, in Patients with Advanced Solid Tumors
Do-Youn Oh1,2, Se-Hoon Lee1,2, Sae-Won Han1,2
1Department 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. 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.
Results:
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.
Conclusion:
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.
Insights
This Phase I trial found that OPB-31121, an oral STAT3 inhibitor, is safe and well-tolerated in patients with advanced solid tumors. The maximum-tolerated dose (MTD) was determined to be 800 mg/day, showing preliminary antitumor activity.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Signal transducer and activator of transcription 3 (STAT3) signaling pathway is implicated in various cancers.
- OPB-31121 is an oral small molecule inhibitor targeting STAT3 with demonstrated preclinical antitumor effects.
Purpose of the Study:
- To evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor efficacy of OPB-31121.
- To determine the maximum-tolerated dose (MTD) of OPB-31121 in patients with advanced solid tumors.
Main Methods:
- A Phase I, dose-escalation study using a standard 3+3 design.
- Patients received OPB-31121 orally once daily for 28 days per cycle with 14 days rest.
- Safety assessed via NCI-CTCAE v3.0; response evaluated by RECIST v1.0.
Main Results:
- Twenty-five patients were treated across five dose levels (100-800 mg).
- The MTD was established at 800 mg/day, with dose-limiting toxicities including vomiting and diarrhea.
- Common adverse events were gastrointestinal, including nausea (84%), vomiting (80%), and diarrhea (72%).
- Preliminary antitumor activity observed, with 8 patients achieving stable disease and 2 showing tumor shrinkage.
Conclusions:
- OPB-31121 demonstrates feasibility for STAT3 inhibition in advanced solid tumors.
- The drug is safe and relatively well-tolerated at the MTD of 800 mg/day.
- OPB-31121 exhibits preliminary antitumor activity, warranting further investigation.
Related Concept Videos
01:11Clinical Trials: Overview
01:15Bioavailability Study Design: Healthy Subjects Versus Patients
02:56Treatment Resistent Cancers