PRT811 Shows Preliminary Efficacy, Consistent Safety in Advanced Glioma and Uveal Melanoma

Source: Targeted Oncology, June 2023

PRT811, a protein arginine methyltransferase 5 (PRMT5) brain-penetrant inhibitor, has exhibited clinical activity and an acceptable safety profile in patients with IDH-positive recurrent, high-grade glioma and splicing mutation (SPLC)-positive uveal melanoma treated in the dose-expansion stage of a phase 1 study (NCT04089449), consistent with findings from the dose-escalation stage of the trial.

Results were presented by Varun Monga, MD, at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. During his presentation, Monga, clinical associate professor of internal medicine-hematology, oncology, and blood and marrow transplantation, Department of Internal Medicine, University of Iowa Carver College of Medicine, stated that although responses occurred in all subgroups assessed, activity was minimal in patients with IDH-negative glioma as well as in those with SPLC-negative uveal melanoma.

PRMT5 overexpression has been shown to induce tumor cell growth, leading to poor clinical outcomes. With its ability to potently and selectively target PRMT5, PRT811 is under investigation in diseases with limited treatment options, including recurrent, high-grade glioma, advanced/metastatic uveal melanoma, and central nervous system lymphomas.