Dr Monga on the Background of Investigating PRT811 in Glioma and Melanoma
Source: OncLive, August 2023
Varun Monga, MD, clinical associate professor, internal medicine, hematology, oncology, and blood and marrow transplantation, University of Iowa, discusses the background for investigating the protein arginine methyltransferase 5 (PRMT5) brain-penetrant inhibitor PRT811 in a phase 1 study (NCT04089449) in patients with recurrent high-grade glioma or uveal melanoma, as well as the agent’s mechanism of action.
In this first-in-human, open-label, multi-center study, investigators aimed to expand on previous data shared regarding the use of PRT811 in high-grade glioma or uveal melanoma. In a previously reported portion of the study, the PRMT5 brain-penetrant inhibitor exhibited beneficial responses in patients who received the agent at 600 mg daily. In an updated readout of the safety and efficacy data that was given at the 2023 ASCO Annual Meeting, investigators shared that treatment with PRT811 exhibited clinical activity in patients with IDH-positive glioma or uveal melanoma with limited treatment options. The agent alsocontinued to show an acceptable safety profile consistent with previous findings. Notably, PRT811 elicited an overall response rate (ORR) of 12.5% in patients with IDH-positive glioma and an ORR of 10% in patients with splicing mutation (SPLC)–positive uveal melanoma.
PRT811 is a novel compound that targets PRMT5, which is highly expressed in patients with glioblastoma and hybrid glioma tumors, as well as in patients whose tumors are SPLC-positive, Monga begins. The activity of PRT811 was previously defined in the phase 1 trial, Monga explains.