Dr Monga on the Investigation of PRT811 in High-Grade Glioma or Uveal Melanoma

Varun Monga, MD, clinical associate professor, Internal Medicine, Hematology, Oncology, and Blood and Marrow Transplantation, University of Iowa, discusses the investigation of the protein arginine methyltransferase 5 (PRMT5) brain-penetrant inhibitor PRT811 in patients with recurrent high-grade glioma or uveal melanoma.

A phase 1 trial (NCT04089449) investigated PRT811 monotherapy in patients with advanced solid tumors, central nervous system lymphoma, or glioma. Data from cohorts of patients with high-grade glioma (n = 38) and uveal melanoma (n = 23) who enrolled in the expansion phase of the trial and received the recommended phase 2 dose of 600 mg of oral PRT811 per day, Monga says. Safety findings were consistent with previous data from the dose-escalation portion of the study, he says. The majority of treatment-emergent adverse effects were grade 1 or 2, and they included gastrointestinal toxicities, fatigue, fall, and myelosuppression.

Efficacy was evaluated by IDH mutation status within the glioma cohort by splicing mutation status in the uveal melanoma cohort, Monga explains.

The overall response (ORR) rate in patients with IDH-positive glioma (n = 16) was 12.5%, with both responders experiencing a complete response. However, no patients responded in the IDH-negative group (n = 22). Those with uveal melanoma group with splicing mutations (n = 10) had an ORR of 10%, with 1 patient achieving a partial response. No patients responded in the group of patients without splicing mutations (n = 13). he expands.

The clinical benefit rate (CBR) was 31.3% for the IDH-mutated glioma population, and it was 4.5% for the IDH-unmutated population. In patients with uveal melanoma, the CBR was 30.0% and 7.7% for the splicing mutation–positive and –negative populations, respectively.