J Rodon, E Rodriguez, M L Maitland, F Y-C Tsai, M A Socinski, J D Berlin, J S Thomas, T Al Baghdadi, I-M Wang, C Guo, M Golmakani, L N Clark, M Gazdoiu, M Li, A W Tolcher
BACKGROUND: Protein arginine methyltransferase 5 (PRMT5) methylates multiple substrates dysregulated in cancer, including spliceosome machinery components. PF-06939999 is a selective small-molecule PRMT5 inhibitor. PATIENTS AND METHODS: This phase I dose-escalation and -expansion trial (NCT03854227) enrolled patients with selected solid tumors. PF-06939999 was administered orally once or twice a day (q.d./b.i.d.) in 28-day cycles. The objectives were to evaluate PF-06939999 safety and tolerability to identify maximum tolerated dose (MTD) and recommended part 2 dose (RP2D), and assess pharmacokinetics (PK), pharmacodynamics [changes in plasma symmetric dimethylarginine (SDMA) levels], and antitumor activities...
April 18, 2024: ESMO Open