A Phase 1 Dose Escalation Study of Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor PRT543 in Patients with Myeloid Malignancies
BLOOD(2021)
摘要
Background: PRMT5 is overexpressed in certain myeloid malignancies and catalyzes symmetric arginine dimethylation of protein substrates that regulate expression of genes associated with disease pathogenesis (Pastore et al. Cancer Discov. 2020). PRT543 is a potent, selective, oral PRMT5 inhibitor with preclinical antitumor activity in acute myeloid leukemia and myeloproliferative neoplasm models (Bhagwat AACR 2020). An open-label phase 1 study of PRT543 in unselected patients (pts) with advanced solid tumors and hematologic malignancies (NCT03886831) is ongoing. Dose escalation results from pts with myeloid malignancies are presented herein.
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