Study of AG-120 and AG-881 in Subjects With Low Grade Glioma

A Phase 1, Multicenter, Randomized, Controlled, Open-Label, Perioperative Study of AG-120 and AG-881 in Subjects With Recurrent, Non-Enhancing, IDH1 Mutant, Low Grade Glioma

Study to evaluate the suppression of 2-HG (2-hydroxyglutarate) in IDH-1 mutant gliomas in resected tumor tissue following pre-surgical treatment with AG-120 or AG-881.

Study Overview

• Status: Completed
• Conditions: Glioma
• Intervention / Treatment: Drug: AG-120; Drug: AG881

Detailed Description

A phase-1, multi-center study in recurrent non-enhancing gliomas with IDH1 R132H mutation for patients who require surgery. The purpose of this study is to evaluate the suppression of 2-HG by comparing the concentration of 2-HG in resected tumors from IDH1 mutant glioma subjects following AG-120 or AG-881 treatment with the 2-HG concentration in untreated, control tumors. The safety, tolerability, PK/PD, and anti tumor activity data from the study in subjects with recurrent non-enhancing Grade 2/3 LGG with an IDH1 R132H mutation for whom surgical resection is indicated will identify the recommended dose of AG-120 and AG-881 for future studies in glioma.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90024
      • United States, California
    • San Francisco, California, United States, 94143
      • United States, California
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • United States, Massachusetts
  • New York
    • New York, New York, United States, 10065
      • United States, New York
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • United States, North Carolina
  • Texas
    • Dallas, Texas, United States, 75390
      • United States, Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be ≥18 years of age.
2. Have histologically or cytologically confirmed recurrent Grade 2 or 3 LGG (oligodendroglioma or astrocytoma according to World Health Organization 2016 classification).
3. Have documented IDH1 R132H gene mutation by local testing and known 1p19q or ATRX mutation status by local testing.
4. Have central confirmation of primarily non-enhancing disease by MRI with less than or equal to 5 mm slice thickness and up to 1 mm interslice gap on either 2D T2 weighted image, 3D T2 weighted image, or FLAIR, with at least 1 non-enhancing tumor measuring 1×1×1 cm.
5. Be candidates for clinical resection but for whom surgery is not urgently indicated (eg, for whom surgery within the next 2-4 months is appropriate).
6. Have KPS of ≥60%
7. Have expected survival of ≥12 months.

Exclusion Criteria:

1. Have received prior systemic anti-cancer therapy within 1 month of the first dose of AG-120 or AG-881 or have received an investigational agent <14 days prior to their first dose of AG-120 or AG-881. In addition, the first dose of AG-120 or AG-881 should not occur before a period of ≥5 half-lives of the investigational agent has elapsed.
2. Have had radiation within 6 months of the first dose of AG-120 or AG-881. (Note: Prior biopsy or surgery is allowed.)
3. Have received any prior treatment with an IDH inhibitor.
4. Have received any prior treatment with bevacizumab (Avastin).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AG-120; AG-120 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle prior to surgery. Following surgery, subjects will have the option to receive treatment with AG-120 .	Drug: AG-120; Prior to surgery subjects will receive AG-120 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects without residual disease following surgery will have the option to receive treatment for up to a year, until disease progression or unacceptable toxicity, whichever occurs first. Subjects with residual disease following surgery will have the option to receive treatment, until disease progression or unacceptable toxicity.
Experimental: AG-881; AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle prior to surgery. Following surgery, subjects will have the option to receive treatment with AG-881.	Drug: AG881; Prior to surgery subjects will receive AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects without residual disease following surgery will have the option to receive treatment for up to a year, until disease progression or unacceptable toxicity, whichever occurs first. Subjects with residual disease following surgery will have the option to receive treatment, until disease progression or unacceptable toxicity.
No Intervention: No Treatment Pre-Surgery; Subjects will not receive treatment prior to surgery. Following surgery, subjects will have the option to receive treatment with AG-120 or AG-881.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
2-HG concentration in surgically resected tumors	Up to 4 weeks, on average

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability: incidence of adverse events and serious adverse events	Up to 48 weeks, on average
Pharmacodynamics of AG-120 or AG-881 measured by 2-HG concentration in plasma.	Up to 4 weeks, on average
Peak Plasma Concentration (Cmax) of AG-120 or AG-881	Up to 4 weeks, on average
Time to maximum concentration (Tmax) of AG-120 or AG-881	Up to 4 weeks, on average
Area Under the Curve (AUC) of AG-120 or AG-881	Up to 4 weeks, on average
Elimination half-life of AG-120 or AG-881	Up to 4 weeks, on average
Clinical activity associated with AG-120 or AG-881 according to modified RANO_LGG criteria.	Up to 48 weeks, on average

Collaborators and Investigators

• Sponsor: Institut de Recherches Internationales Servier

Publications and helpful links

General Publications

• Mellinghoff IK, Lu M, Wen PY, Taylor JW, Maher EA, Arrillaga-Romany I, Peters KB, Ellingson BM, Rosenblum MK, Chun S, Le K, Tassinari A, Choe S, Toubouti Y, Schoenfeld S, Pandya SS, Hassan I, Steelman L, Clarke JL, Cloughesy TF. Vorasidenib and ivosidenib in IDH1-mutant low-grade glioma: a randomized, perioperative phase 1 trial. Nat Med. 2023 Mar;29(3):615-622. doi: 10.1038/s41591-022-02141-2. Epub 2023 Feb 23.

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2018
• Primary Completion (Actual): August 2, 2019
• Study Completion (Actual): March 28, 2025

Study Registration Dates

• First Submitted: November 7, 2017
• First Submitted That Met QC Criteria: November 9, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Glioma; IDH1; AG-120; AG-881
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; ivosidenib
• Other Study ID Numbers: AG120-881-C-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

• IPD Sharing Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• IPD Sharing Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Individual Participant Data Set
2. Study Protocol
3. Statistical Analysis Plan
4. Informed Consent Form
5. Clinical Study Report
6. Study-level clinical trial data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes