NCT07464925

A Phase 1 Safety and Dose Finding Study of GLIX1 in Adults With Recurrent or Progressive High-grade Glioma

An Open-Label Phase 1 Safety and Dose Finding Study of Orally Administered GLIX1 in Adults With Recurrent or Progressive High-grade Glioma

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Tetragon Biosciences Ltd · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label, multicenter dose-escalation study to be followed by a dose expansion to define the optimal dose of GLIX1 as monotherapy by reviewing safety and tolerability, disease characteristics and pharmacokinetic profiles and preliminary clinical activity in participants with a high grade diffuse glioma that progressed during or recurred after prior standard of care therapies or investigational therapies as clinically indicated. Patients will be treated daily with GLIX1 capsules until disease progression or unacceptable safety.

Detailed description

Glioblastomas (GBMs) are the most common and aggressive primary malignant tumors in adult central nervous system. High-grade glioma almost always recur and/or progress, and upon progression treatment options are very limited with no universal standard therapy established. GLIX1 is a small molecule administered PO (per os, i.e., orally), that targets the deoxyribonucleic acid (DNA) damage repair mechanism by enhancing Tet methylcytosine dioxygenase 2 (TET2) activity. Increasing the activity of the TET2 enzyme increases DNA oxidation at 5-methylcytosine residues. Such oxidation is normally processed by base excision repair. During base excision repair, a single stranded DNA break is formed. These single strand DNA breaks are well tolerated in normal cells. In cancer, alterations in DNA methylation are common and TET2 activity is inhibited, giving rise to increased DNA methylation in close genomic proximity. When GLIX1 agonizes TET2 activity in cancer cells, excessive base excision repair results in numerous single strand DNA breaks in close proximity, which ultimately converge to form double strand DNA breaks that overwhelm the repair capacity of these cancer cells, resulting in apoptotic cell death. High-grade glioma have some of the lowest levels of genomic 5-hydroxymethylcytosine. Thus, enhancing the activity of the TET2 enzyme in these cells is likely to have the greatest effect in terms of treating cancers. Indeed, GLIX1 has been shown to cross the blood brain barrier in rodents and has shown significant activity in various in vitro and in vivo GBM and glioma tumor models.

Conditions

• Glioblastoma Multiforme of Brain
• Glioma
• Glioblastoma

Interventions

Type	Name	Description
DRUG	GLIX1	Administered orally, once daily, in cycles of 28 days

Timeline

• Start date: 2026-03-01
• Primary completion: 2027-06-01
• Completion: 2027-12-01
• First posted: 2026-03-11
• Last updated: 2026-03-20

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study