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Updated: Dec 25, 2025
Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies
Published on: June 20, 2015
Phase 1 study of napabucasin, a cancer stemness inhibitor, in patients with advanced solid tumors
Akihito Kawazoe1, Yasutoshi Kuboki1, Hideaki Bando1
1Department of Gastroenterology and Gastrointestinal Oncology Division, National Cancer Center Hospital East, Kashiwa, Japan.
Purpose:
Napabucasin is a cancer stemness inhibitor that targets a number of oncogenic pathways, including signal transducer and activator of transcription 3 (STAT3). Phase 1/2 studies suggest tolerability and anti-tumor activity in various types of cancer; a Phase 3 study of napabucasin plus standard therapy in colorectal cancer is ongoing. This is a Phase 1 dose-escalation study in patients with advanced solid tumors, and the first study of napabucasin in Japanese patients.
Methods:
Patients received napabucasin 480, 960, or 1440 mg daily in 28-day cycles until disease progression or intolerable toxicity. Primary objectives were to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and the pharmacokinetic (PK) profile of napabucasin. Blood samples were taken for PK analysis on Days 1, 2, 8, and 15 of Cycle 1, and Days 29 and 30 of Cycle 2. Secondary objectives were to assess napabucasin antitumor activity, and the relationship between biomarkers and antitumor activity. JapicCTI-No: JapicCTI-132152.
Results:
Enrolled were 14 patients (480 mg [n = 3], 960 mg [n = 4], 1440 mg [n = 7]). One patient experienced a DLT (Grade 3, anorexia). MTD was 1440 mg/day. Most common drug-related adverse events were diarrhea (n = 9), nausea (n = 4), vomiting (n = 3), and anorexia (n = 3). Napabucasin showed a similar PK profile to previous studies and no abnormal accumulation was observed. Following treatment, two patients had stable disease; the remaining 12 had progressive disease.
Conclusion:
Napabucasin was well-tolerated at doses up to 1440 mg/day in Japanese patients with advanced solid tumors; the PK profile was comparable to that reported previously.
Insights
Napabucasin, a cancer stemness inhibitor, was well-tolerated in Japanese patients with advanced solid tumors up to 1440 mg/day. Pharmacokinetics were consistent with prior studies, supporting further clinical investigation.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Napabucasin is a novel cancer stemness inhibitor targeting oncogenic pathways like STAT3.
- Previous studies indicate tolerability and anti-tumor activity in various cancers.
Purpose of the Study:
- To evaluate the safety, tolerability, and pharmacokinetics of napabucasin in Japanese patients with advanced solid tumors.
- To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs).
Main Methods:
- Phase 1 dose-escalation study involving 14 patients receiving napabucasin at 480, 960, or 1440 mg daily.
- Primary objectives included DLT assessment, MTD determination, and pharmacokinetic profiling.
- Secondary objectives assessed anti-tumor activity and biomarker correlations.
Main Results:
- The MTD was determined to be 1440 mg/day.
- Most common adverse events included diarrhea, nausea, and anorexia.
- Napabucasin exhibited a comparable pharmacokinetic profile to previous studies without abnormal accumulation.
Conclusions:
- Napabucasin is well-tolerated up to 1440 mg/day in Japanese patients with advanced solid tumors.
- The pharmacokinetic profile is consistent with prior findings.
- The study supports the continued development of napabucasin.
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