GliomaPhase 1NCT02481154
Study of Orally Administered AG-881 in Patients With Advanced Solid Tumors, Including Gliomas, With an IDH1 and/or IDH2 Mutation
A Phase 1 study testing AG881 in people with Glioma, run by Institut de Recherches Internationales Servier at 9 sites in United States.
Trial summary
This study evaluates the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-881 in Gliomas, that harbor an IDH1 and/or IDH2 mutation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioma
- What is being tested?
- AG881
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 9 sitesUnited States
- Study dates
- Jun 2015to 19 Jun 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
Who may be able to join
- Patient must be ≥18 years of age
- Patient must have histologically or cytologically confirmed solid tumor, including glioma, with documented IDH1 and/or IDH2 gene-mutation. Patients in the dose escalation phase must have disease that has recurred or progressed following standard therapy and/or therapy with an inhibitor of mutant IDH1 and/or IDH2, or that has not responded to this therapy. Patients in the expansion phase may have previously untreated disease
- Patient must have evaluable disease by RECIST v1.1 for patients without glioma or by RANO or RANO LGG criteria for patients with glioma
- Patients with glioma must have a baseline brain MRI scan
- Patient must have archived primary tumor biopsies or surgical specimens, or biopsies of recurrent or metastatic samples
- Patient must be amenable to serial peripheral blood sampling, urine sampling, and tumor biopsies during the study
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- Patient must be able to understand and willing to sign an informed consent
- Patient must have ECOG PS of 0 to 2
- Patient must have expected survival of ≥3 months
- Patient must have adequate bone marrow function as evidenced by absolute neutrophil count ≥1.5 ×10^9/L; hemoglobin >9 g/dL (Patients are allowed to be transfused to this level); platelets ≥75 × 10^9/L
- Patient must have adequate hepatic function as evidenced by: Serum total bilirubin ≤1.5 × upper limit of normal (ULN), unless considered due to Gilbert's disease or disease involvement; Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤2.5 × ULN. For patients with bone metastases and/or suspected disease-related liver or biliary involvement, AST, ALT and ALP must be ≤5 × ULN
- Patient must have adequate renal function as evidenced by: Serum creatinine ≤2.0 × ULN or Creatinine clearance >40 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimated: (140-Age) x (weight in kg) x (0.85 if female)/72 x serum creatinine
- Patient must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer
- Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to first study drug administration. Patients with reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy or tubal occlusion or who have not experienced natural menopause (i.e., who have not menstruated at all) for at least 24 consecutive months (i.e., have had menses at any time in the preceding 24 consecutive months). Women with reproductive potential as well as fertile men and their partners who are female with reproductive potential must agree to abstain from sexual intercourse or to use two highly effective forms of contraception from the time of giving informed consent, during the study, and for 90 days (females and males) following the last dose of AG 881
Who cannot join
- Patients who received systemic anticancer therapy or radiotherapy <21 days prior to their first day of study drug administration
- Patients who received an investigational agent (including AG-120 or AG-221) <14 days prior to their first day of study drug administration. In addition, the first dose of AG-881 should not occur before a period ≥5 half-lives of the investigational agent (other than AG-120 or AG-221) has elapsed.
- Patients with gliomas who have had prior treatment with bevacizumab (Avastin) are excluded
- Patients who are pregnant or breast feeding
- Patients with an active severe infection that required anti-infective therapy or with an unexplained fever >38.5°C during screening visits or on their first day of study drug administration (at the discretion of the Investigator, patients with tumor fever may be enrolled)
- Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF <40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan obtained within approximately 28 days of C1D1
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- Patients with a history of myocardial infarction within the 6 months prior to screening
- Patients with known unstable or uncontrolled angina pectoris
- Patients with a known history of severe and/or uncontrolled ventricular arrhythmias
- Patients with QTc interval ≥450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome)
- Patients taking medications that are known to prolong the QT interval unless they can be transferred to other medications within ≥5 half-lives prior to dosing, or unless the medications can be properly monitored during the study.
- Patients with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C
- Patients with known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
- Patients with brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery, or other therapy, including those used to control symptoms, within 1 month of first dose
- Glioma patients with evidence of intracranial or intratumoral hemorrhage either by MRI or CT scan
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
UT Southwestern Medical Center
Dallas, Texas, 77030
Duke University Medical Center
Durham, North Carolina, 27710
MD Anderson Cancer Center
Houston, Texas, 75390
UCLA Oncology Center
Los Angeles, California, 90024
University of Miami
Miami, Florida, 33136
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of California San Francisco
San Francisco, California, 94143
About this study
Official title: A Phase 1, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered AG-881 in Patients With Advanced Solid Tumors, Including Gliomas, With an IDH1 and/or IDH2 Mutation
This study evaluates the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-881 in Gliomas, that harbor an IDH1 and/or IDH2 mutation.
Read the detailed description
The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-881 in gliomas, that harbor an IDH1and/or IDH2 mutation. The first portion of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of AG-881 to determine the maximum tolerated dose (MTD) and/or the recommended Phase II dose. The second portion of the study is a dose expansion phase where patients will receive AG-881 to further evaluate the safety, tolerability, and clinical activity of the recommended Phase II dose. The anticipated time on study treatment is until disease progression, unacceptable toxicity occurs or the patient is removed at the discretion of the investigator
- Conditions
- Glioma
- Being tested
- AG881
- Keywords
- Glioma, IDH1, IDH2, Dual Mutation, AG-881
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AG881Drug
AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Patients may continue treatment with AG-881 until disease progression or development of other unacceptable toxicity
| Study group | Role | What they receive |
|---|---|---|
| AG881 | Experimental | AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Patients may continue treatment with AG-881 until disease progression, development of other unacceptable toxicity or Investigator discretion Receives: Drug: AG881 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety/Tolerability; incidence of adverse events
Measured: Up to 26 weeks, on average
Maximum Tolerated Dose and/or the recommended Phase II dose of AG881 in patients with advance solid tumors, including gliomas
Measured: Up to 26 weeks, on average
Secondary outcomes (4)
Pharmacokinetic profiles including max concentration (Cmax), time to maximum concentration (Tmax), AUC, and elimination half-life
Measured: Up to 26 weeks, on average
Pharmacodynamic levels of AG-881
Measured: Up to 26 weeks, on average
Pharmacodynamic levels of 2-HG
Measured: Up to 26 weeks, on average
Clinical Activity according to RECIST v 1.1 (2009) for patients with solid tumors, by RANO (2010) criteria for patients with glioma
Measured: Up to 26 weeks, on average
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2015 (estimated)
- Study startJun 2015
- Primary completion17 Oct 2022
- Study completion19 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GliomaStudies 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
- Single group
- Masking
- None (open label)
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut de Recherches Internationales Servier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02481154
- Sponsor's protocol ID
- AG881-C-002
- Status last verified
- Feb 2026
- First submitted
- 16 Jun 2015
- Last updated
- 17 Feb 2026
- Results posted
- No
- Individual data sharing
- Yes: Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * sponsored by Servier * with a first patient enrolled as of 1 January 2004 onwards * for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
Publications
Mellinghoff IK, Penas-Prado M, Peters KB, Burris HA 3rd, Maher EA, Janku F, Cote GM, de la Fuente MI, Clarke JL, Ellingson BM, Chun S, Young RJ, Liu H, Choe S, Lu M, Le K, Hassan I, Steelman L, Pandya SS, Cloughesy TF, Wen PY. Vorasidenib, a Dual Inhibitor of Mutant IDH1/2, in Recurrent or Progressive Glioma; Results of a First-in-Human Phase I Trial. Clin Cancer Res. 2021 Aug 15;27(16):4491-4499. doi: 10.1158/1078-0432.CCR-21-0611. Epub 2021 Jun 2.
PubMed 34078652
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered AG-881 in Patients With Advanced Solid Tumors, Including Gliomas, With an IDH1 and/or IDH2 Mutation
- ClinicalTrials.gov ID
- NCT02481154
- Acronym / sponsor ID
- AG881-C-002
- Conditions
- Glioma
- Keywords
- Glioma, IDH1, IDH2, Dual Mutation, AG-881
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- Institut de Recherches Internationales ServierUniversity, hospital or other
- Study start
- Jun 2015 (actual)
- Primary completion
- 17 Oct 2022 (actual)
- Study completion
- 19 Jun 2024 (actual)
- First posted
- 25 Jun 2015 (estimated)
- 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 study evaluates the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-881 in Gliomas, that harbor an IDH1 and/or IDH2 mutation.
Detailed description
The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-881 in gliomas, that harbor an IDH1and/or IDH2 mutation. The first portion of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of AG-881 to determine the maximum tolerated dose (MTD) and/or the recommended Phase II dose. The second portion of the study is a dose expansion phase where patients will receive AG-881 to further evaluate the safety, tolerability, and clinical activity of the recommended Phase II dose. The anticipated time on study treatment is until disease progression, unacceptable toxicity occurs or the patient is removed at the discretion of the investigator
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AG881 | Experimental | Drug: AG881AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Patients may continue treatment with AG-881 until disease progression, development of other unacceptable toxicity or Investigator discretion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patient must be ≥18 years of age
- Patient must have histologically or cytologically confirmed solid tumor, including glioma, with documented IDH1 and/or IDH2 gene-mutation. Patients in the dose escalation phase must have disease that has recurred or progressed following standard therapy and/or therapy with an inhibitor of mutant IDH1 and/or IDH2, or that has not responded to this therapy. Patients in the expansion phase may have previously untreated disease
- Patient must have evaluable disease by RECIST v1.1 for patients without glioma or by RANO or RANO LGG criteria for patients with glioma
- Patients with glioma must have a baseline brain MRI scan
- Patient must have archived primary tumor biopsies or surgical specimens, or biopsies of recurrent or metastatic samples
Key exclusion criteria (15 listed)
- Patients who received systemic anticancer therapy or radiotherapy <21 days prior to their first day of study drug administration
- Patients who received an investigational agent (including AG-120 or AG-221) <14 days prior to their first day of study drug administration. In addition, the first dose of AG-881 should not occur before a period ≥5 half-lives of the investigational agent (other than AG-120 or AG-221) has elapsed.
- Patients with gliomas who have had prior treatment with bevacizumab (Avastin) are excluded
- Patients who are pregnant or breast feeding
- Patients with an active severe infection that required anti-infective therapy or with an unexplained fever >38.5°C during screening visits or on their first day of study drug administration (at the discretion of the Investigator, patients with tumor fever may be enrolled)
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 |
|---|---|---|
| AG881AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Patients may continue treatment with AG-881 until disease progression or development of other unacceptable toxicity | Drug | AG881 |
Primary outcome
Safety/Tolerability; incidence of adverse events
Time frame: Up to 26 weeks, on average
Maximum Tolerated Dose and/or the recommended Phase II dose of AG881 in patients with advance solid tumors, including gliomas
Time frame: Up to 26 weeks, on average
4 secondary outcomes
Pharmacokinetic profiles including max concentration (Cmax), time to maximum concentration (Tmax), AUC, and elimination half-life
Time frame: Up to 26 weeks, on average
Pharmacodynamic levels of AG-881
Time frame: Up to 26 weeks, on average
Pharmacodynamic levels of 2-HG
Time frame: Up to 26 weeks, on average
Clinical Activity according to RECIST v 1.1 (2009) for patients with solid tumors, by RANO (2010) criteria for patients with glioma
Time frame: Up to 26 weeks, on average
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
- Derived from this study: PubMed 34078652Mellinghoff IK, Penas-Prado M, Peters KB, Burris HA 3rd, Maher EA, Janku F, Cote GM, de la Fuente MI, Clarke JL, Ellingson BM, Chun S, Young RJ, Liu H, Choe S, Lu M, Le K, Hassan I, Steelman L, Pandya SS, Cloughesy TF, Wen PY. Vorasidenib, a Dual Inhibitor of Mutant IDH1/2, in Recurrent or Progressive Glioma; Results of a First-in-Human Phase I Trial. Clin Cancer Res. 2021 Aug 15;27(16):4491-4499. doi: 10.1158/1078-0432.CCR-21-0611. Epub 2021 Jun 2.
- Individual participant dataSharing planned: Yes. Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * sponsored by Servier * with a first patient enrolled as of 1 January 2004 onwards * for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
9 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 AG881 in people with Glioma, run by Institut de Recherches Internationales Servier at 9 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?
The sponsor lists 14 inclusion and 15 exclusion criteria. 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: finished, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety/Tolerability; incidence of adverse events (time frame: Up to 26 weeks, on average). 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?
On the ClinicalTrials.gov record for NCT02481154, which also lists 1 linked publication.
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 17 Feb 2026.