University of California San Francisco
Helen Diller Family Comprehensive Cancer Center

New Clinical Trial Targets Mutations Commonly Found in Lower Grade Gliomas

By | February 12, 2020

New Clinical Trial Targets Mutations Commonly Found in Lower Grade Gliomas

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

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.

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

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.