NCT07144254

Tegavivint With Gemcitabine in Patients With Relapsed or Refractory Osteosarcoma

Study of Tegavivint, a Transducin Beta-like Protein 1 (TBL1) Inhibitor, With Gemcitabine in Patients With Relapsed or Refractory Osteosarcoma

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 1 Year – 30 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to define the maximum tolerated dose (MTD) and/or Recommended phase 2 dose (RP2D) of Tegavivint in combination with Gemcitabine in patients with relapsed or refractory osteosarcoma (OS). The study will also investigate the toxicities of Tegavivint in combination with gemcitabine in patients with relapsed or refractory OS.

Detailed description

Recurrent osteosarcoma (OS) has a poor prognosis, with 5-year overall survival after relapse ranging from 13% to 45%. There are currently no chemotherapy agents proven to significantly improve survival in relapsed or refractory OS, particularly in patients with unresectable disease, highlighting the need for new treatments. Tegavivint is a first-in-class small molecule that targets the Wnt/beta-catenin signaling pathway by inhibiting the TBL1-beta-catenin complex, leading to beta-catenin degradation and suppression of oncogenic transcription without affecting its normal cellular functions. Tegavivint showed potent anti-tumor activity in OS cell lines and mouse models, inhibiting tumor growth and metastasis, including activity against chemoresistant and cancer stem-like cells. Recent clinical data shows: Adults: In a Phase 1/2a trial (NCT03459469) with 24 patients, tegavivint at 5 mg/kg (3 weeks on/1 week off) was well tolerated with no dose-limiting toxicities. Most side effects were mild (fatigue, nausea, headache), and serious toxicities common to other Wnt inhibitors were not seen. Tumor shrinkage (\>50%) occurred in five patients, with others achieving prolonged stable disease. Pediatrics: In an ongoing COG Phase 1/2 trial (NCT04851119), tegavivint was tested in 10 patients at 5 and 6.5 mg/kg. No DLTs were observed, and the recommended dose was set at 6.5 mg/kg. Most side effects were grade 1-2; grade ≥3 events were infrequent.

Conditions

• Osteosarcoma Recurrent
• Osteosarcoma in Children
• Relapsed Osteosarcoma
• Refractory Osteosarcoma

Interventions

Type	Name	Description
DRUG	Tegavivint	Tegavivint will be administered second, IV over 4 hours, on days 1, 8, and 15 at the dose level assigned at study entry Cycle length will be 21 days. A cycle may be repeated for a total of 17 cycles, up to a total duration of therapy of approximately 12 months.
DRUG	Gemcitabine	Gemcitabine will be administered first, intravenously (IV) over 60 minutes, on days 1 and 8 at a fixed dose of 1000 mg/m2

Timeline

• Start date: 2026-01-22
• Primary completion: 2028-05-01
• Completion: 2028-05-01
• First posted: 2025-08-27
• Last updated: 2026-03-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study