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NCT Number: NCT03343197

Study of AG-120 and AG-881 in Subjects With 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.

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Key information

Conditions

Glioma Neoplasms Neoplasms by Histologic Type Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neuroectodermal Tumors

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

United States, California, Los Angeles, California, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Be ≥18 years of age.
  • Have histologically or cytologically confirmed recurrent Grade 2 or 3 LGG (oligodendroglioma or astrocytoma according to World Health Organization 2016 classification).
  • Have documented IDH1 R132H gene mutation by local testing and known 1p19q or ATRX mutation status by local testing.
  • 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.
  • 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).
  • Have KPS of ≥60%
  • Have expected survival of ≥12 months.

Exclusion criteria

  • 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.
  • Have had radiation within 6 months of the first dose of AG-120 or AG-881. (Note: Prior biopsy or surgery is allowed.)
  • Have received any prior treatment with an IDH inhibitor.
  • Have received any prior treatment with bevacizumab (Avastin).

Treatment and study plan

AG-120

Drug

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.

AG881

Drug

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.

Primary outcomes

  1. 2-HG concentration in surgically resected tumors

    Time frame: Up to 4 weeks, on average

Secondary outcomes

  1. Safety and tolerability: incidence of adverse events and serious adverse events

    Time frame: Up to 48 weeks, on average

  2. Pharmacodynamics of AG-120 or AG-881 measured by 2-HG concentration in plasma.

    Time frame: Up to 4 weeks, on average

  3. Peak Plasma Concentration (Cmax) of AG-120 or AG-881

    Time frame: Up to 4 weeks, on average

  4. Time to maximum concentration (Tmax) of AG-120 or AG-881

    Time frame: Up to 4 weeks, on average

  5. Area Under the Curve (AUC) of AG-120 or AG-881

    Time frame: Up to 4 weeks, on average

  6. Elimination half-life of AG-120 or AG-881

    Time frame: Up to 4 weeks, on average

  7. Clinical activity associated with AG-120 or AG-881 according to modified RANO_LGG criteria.

    Time frame: Up to 48 weeks, on average

Sponsors and collaborators

Lead sponsor

Institut de Recherches Internationales Servier

Other

Registry information

Official study title

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

Important dates

Study start
2018
Primary completion
2019
Study completion
2025
First posted
Nov 17, 2017
Registry last updated
Feb 17, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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