diffuse astrocytoma

New Clinical Trial Targets Mutations Commonly Found in Lower Grade Gliomas

Within the next few months, the UCSF Brain Tumor Center will begin recruiting for a multi-center clinical trial to evaluate AG-881, a small molecule drug, for treatment of residual or recurrent IDH-mutant grade II glioma

AG-881 is a drug that inhibits the mutated forms of the isocitrate dehydrogenase (IDH) 1 and 2 proteins. IDH1 and IDH2 gene mutations are commonly found across a variety of cancers, including glioma. In the last decade, the discovery of these mutations and their role in brain tumor growth and biology has led to a sweeping re-organization of the World Health Organization (WHO) classification system. Now, certain glioma subtypes are further defined based on their IDH mutation status – a distinction that greatly impacts tumor biology and patient outcomes.

mutant IDH1 structure
The molecular structure of the IDH1 protein with a depiction of the R132H mutation. 

IDH mutations are known to be an early driver of glioma development, though the exact mechanism by which that occurs remains elusive.  AG-881 acts to counter the overactive proteins produced within tumor cells carrying either of those mutations. “With IDH mutations present in the majority of low-grade gliomas, being able to specifically target this known driver of tumor development could have enormous impact,” says UCSF neuro-oncologist Jennifer Clarke, MD, who is leading the study at UCSF. 

Jennifer Clarke, MD
UCSF neuro-oncologist Jennifer Clarke, MD

Preliminary findings from a phase I study of AG-881 show promising results for patients with IDH-mutant glioma. For patients with non-enhancing tumor, average six-month volumetric tumor growth was 6.8% following AG-881 treatment, compared to 24.5% in a similar glioma population without treatment.  In addition, preliminary findings from a second, surgical study of AG-881 showed good brain penetration of the drug. 

In this phase III trial, approximately 360 participants across multiple study sites will receive daily doses of the orally administered drug (or a placebo), with their treatment response followed. To be eligible, patients must have residual or recurrent grade II astrocytoma or oligodendroglioma with confirmed mutation(s) in IDH1 or IDH2, and be between 1 and 5 years from their most recent surgery.   


For More Information on Enrollment

Study of AG-881 in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation 
(415) 353-2966


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