Study of AG-120 and AG-881 in Subjects with Low Grade Glioma
This clinical trial will evaluate the safety, tolerability, and anti-tumor activity of AG-120 or AG-881, when administered to patients with recurrent low-grade glioma before surgery.
AG-120 is an orally administered drug that specifically inhibits a mutated form of IDH1, which is commonly mutated in a variety of cancers. Mutant IDH1 drives tumor growth in part by producing a molecule called 2HG. AG-120 is designed to inhibit mutant IDH1, and therefore the formation of 2-HG.
AG-881 is an orally administered drug that inhibits the mutated forms of both IDH1 and IDH2 proteins, which are both found in a variety of cancers. Mutant IDH1 and IDH2 proteins both contribute to increased formation of 2HG, so AG-881 acts to ultimately inhibit 2HG production. The suppression of 2HG-mediated signaling is thought to inhibit cell growth in tumor cells with IDH mutations.
Specifically, this study will examine 2-HG concentrations in resected tumor tissue to evaluate how well AG-120 and/or AG-881 suppress 2-HG levels when administered prior to surgery. 2-HG levels in the groups receiving AG-120 or AG-881 will be compared to resected tumor tissue from participants that did not receive treatment with either of these drugs. Eligible participants will be randomly assigned to one of the following groups:
- Experimental Group 1: AG-120 prior to surgery
- Experimental Group 2: AG-881 prior to surgery
- No Intervention: No treatment prior to surgery
- 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
- 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)