Glioblastoma Multiforme of BrainPhase 1NCT07464925
A Phase 1 Safety and Dose Finding Study of GLIX1 in Adults With Recurrent or Progressive High-grade Glioma
A Phase 1 study testing GLIX1 in people with Glioblastoma Multiforme of Brain and Glioma, run by Tetragon Biosciences Ltd at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme of Brain, Glioma, Glioblastoma
- What is being tested?
- GLIX1
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 4 sitesUnited States
- Study dates
- 20 Apr 2026to Dec 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Main Inclusion Criteria:
- Adult patients aged ≥18 years at the time of informed consent
- Participants must have histologically confirmed Grade 3 or Grade 4 glioma
- Recurrent or progressive disease
- A maximum of two prior treatment lines
- Interval of at least 3 months since the last day off of radiotherapy, unless tumor progression and index lesion is outside the prior radiation field.
- Interval since last dose of systemic therapy and Baseline MRI of ≥28 days, except:
- for nitrosoureas (e.g., lomustine, carmustine, fotemustine): 42 days (6 weeks)
- for monoclonal antibodies: 42 days (6 weeks)
- for small molecules, 4 weeks or at least 5 half-lives (whatever is longer)
- Recovered from all toxicities from prior treatments to Grade 1 or less by NCI CTCAE v6.0:
- Participants receiving corticosteroids must be on a stable or decreasing dose of ≤6 mg daily dexamethasone (or ≤40 mg prednisone) for the 7 days prior to the start of study treatment.
- Participants with seizures must be adequately controlled on a stable regimen of anti-epileptic drugs.
- Adequate performance status: Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Ability to swallow tablets or capsules.
- Adequate hematological, liver and renal function.
- Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to first dosing. Women must use a highly effective form of contraception (with Pearl Index <1%) for the duration of the study and for at least 3 months after the last dose of study medication.
- Men with partners of childbearing potential must be willing to use condoms in combination with a second effective method of contraception by the partner during the study and for at least 3 months after the last dose of study medication.
Main Exclusion Criteria:
- Known contraindication for gadolinium (Gd) based, contrast-enhanced MRI
- Prior history of another invasive malignancy unless a complete remission was achieved at least 3 years prior to enrolment AND no additional therapy is required during the study period, except for anti-estrogen or androgen therapy and/or bisphosphonates or denosumab.
- Participants with known active or uncontrolled infection, and/or unexplained fever >38°C in the 3 days prior to the start of study treatment.
- Major non-tumor related surgical procedure or significant traumatic injury within 28 days prior to signing of consent.
- Receiving any investigational products (defined as treatment for which there is currently no regulatory authority-approved indication) within 4 weeks or 5 half-lives (whichever is the longest) prior to Baseline MRI.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 4 recruiting
- Recruiting
Northwestern Medicine
Chicago, Illinois, 60611
Ditte Primdahl, MD, 312-695-1202, cancer@northwestern.edu
- Recruiting
NYU Langone Health
New York, New York, 10016
Alexandra Miller, MD, (212) 731-6267, cancertrials@nyulangone.org
Alexandra Miller, MD, PhD
- Recruiting
Stanford University
Palo Alto, California, 94304
Lewis Naya, (650) 725-0379, secure-sci-cto-neuro-crcs@lists.stanford.edu
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Patrick Grogan, MD, 813-745-8000, Patrick.grogan@moffitt.org
Patrick Grogan, MD
About this study
Official title: An Open-Label Phase 1 Safety and Dose Finding Study of Orally Administered GLIX1 in Adults With Recurrent or Progressive High-grade Glioma
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.
Read the 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
- Being tested
- GLIX1
- Keywords
- GLIX1, Glioma, GBM, Glioblastoma, TET2
- Medical subject headings
- Glioma, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GLIX1Drug
Administered orally, once daily, in cycles of 28 days
| Study group | Role | What they receive |
|---|---|---|
| GLIX1 | Experimental | Escalating doses of GLIX1, starting at a dose of 1000 mg/day Receives: Drug: GLIX1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Profile of GLIX1 (%Participants with Treatment-emergent Adverse Events)
%Participants with treatment-emergent adverse events (TEAEs) based on CTCAE v6.0
Measured: From first administration of GLIX1 (Cycle 1 Day 1) until 30 days following last dose administration
Maximal Tolerated Dose and/or Recommended Dose
Maximal Tolerated Dose (MTD) is selected as the dose for which the isotonic estimate of the Dose Limiting Toxicity (DLT) rate is closest to the target rate of 0.3
Measured: From first administration of GLIX1 (Cycle 1 Day 1) until one cycle of 28 days is complete
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2026
- Study start20 Apr 2026
- Primary completionJun 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma Multiforme of BrainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- This is a first in human, open-label, multicenter dose-escalation study followed by a dose expansion cohort, designed to define the recommended dose of GLIX1 in participants with a high grade glioma that progressed during or recurred after prior treatment. The study will employ the Bayesian Optimal Interval (BOIN) design to guide dose escalation/de-escalation decisions based on Dose Limiting Toxicities.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tetragon Biosciences Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07464925
- Sponsor's protocol ID
- GLIX1-C101
- Status last verified
- Nov 2026
- First submitted
- 2 Mar 2026
- Last updated
- 4 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Phase 1 Safety and Dose Finding Study of Orally Administered GLIX1 in Adults With Recurrent or Progressive High-grade Glioma
- ClinicalTrials.gov ID
- NCT07464925
- Acronym / sponsor ID
- GLIX1-C101
- Conditions
- Glioblastoma Multiforme of Brain, Glioma, Glioblastoma
- Keywords
- GLIX1, Glioma, GBM, Glioblastoma, TET2
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Tetragon Biosciences LtdIndustry (pharma, biotech, devices)
- Study start
- 20 Apr 2026 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 11 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a first in human, open-label, multicenter dose-escalation study followed by a dose expansion cohort, designed to define the recommended dose of GLIX1 in participants with a high grade glioma that progressed during or recurred after prior treatment. The study will employ the Bayesian Optimal Interval (BOIN) design to guide dose escalation/de-escalation decisions based on Dose Limiting Toxicities.
| Arm | Type | Receives |
|---|---|---|
| GLIX1 | Experimental | Drug: GLIX1Escalating doses of GLIX1, starting at a dose of 1000 mg/day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GLIX1Administered orally, once daily, in cycles of 28 days | Drug | GLIX1 |
Primary outcome
Safety Profile of GLIX1 (%Participants with Treatment-emergent Adverse Events)
Time frame: From first administration of GLIX1 (Cycle 1 Day 1) until 30 days following last dose administration
%Participants with treatment-emergent adverse events (TEAEs) based on CTCAE v6.0
Maximal Tolerated Dose and/or Recommended Dose
Time frame: From first administration of GLIX1 (Cycle 1 Day 1) until one cycle of 28 days is complete
Maximal Tolerated Dose (MTD) is selected as the dose for which the isotonic estimate of the Dose Limiting Toxicity (DLT) rate is closest to the target rate of 0.3
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Stanford University
Palo Alto, United States
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GLIX1 in people with Glioblastoma Multiforme of Brain and Glioma, run by Tetragon Biosciences Ltd at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety Profile of GLIX1 (%Participants with Treatment-emergent Adverse Events) (time frame: From first administration of GLIX1 (Cycle 1 Day 1) until 30 days following last dose administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.