Date: 2016-09-15
Type of information: Initiation of the trial
phase: 1
Announcement: initiation of the trial
Company: GSK (UK)
Product: GSK3326595
Action
mechanism: enzyme inhibitor/protein arginine methyltransferase 5 (PRMT5) inhibitor. PRMT5 is a protein arginine methyltransferase (PRMT) that is reported to have a role in diverse cellular processes, including tumorigenesis. PRMT5 overexpression is observed in cell lines and primary patient samples derived from a number of cancers, including lymphomas, lung cancer, breast cancer and colorectal cancer. GSK3326595 (formerly EPZ015938), a highly selective and orally bioavailable small molecule, is the first PRMT5 inhibitor and the third epigenetic investigational therapy derived from Epizyme's proprietary discovery platform to enter the clinic.
Disease: solid tumors, non-Hodgkin's lymphoma
Therapeutic area: Cancer - Oncology
Country: Canada, France, Netherlands, USA
Trial
details: The study is a first time in human (FTIH), open-label, dose escalation study that will assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of GSK3326595 in subjects with advanced or recurrent solid tumors, as well as clinical activity in subjects with a subset of solid tumors and non-Hodgkin's lymphoma. This is an open-label, repeat-dose, multicenter, 2-part study to establish the maximally tolerated dose (MTD)/ recommended phase 2 dose (RP2D) based on safety and tolerability and preliminary clinical efficacy of orally-administered GSK3326595. Part 1 is a dose-escalation phase to identify the MTD/RP2D based on the safety, PK, and PD profiles observed after oral administration of GSK3326595. This Part will be conducted in adult subjects with relapsed and/or refractory solid tumors. It is estimated that up to 42 subjects will be enrolled into the dose escalation cohort of the study, including up to 30 subjects to identify the MTD and approximately 12 subjects in the PK/PD/metabolite/biomarker expansion cohort(s). Disease-specific expansion cohorts (Part 2) are planned to further explore clinical activity of GSK3326595 in subjects with selected solid tumors and non-Hodgkin's lymphomas. It is estimated that up to 138 subjects will be enrolled in the disease-specific expansion cohorts of the study. The duration of study will depend on recruitment rates and the timing of subjects' duration on study (withdrawal rates due to toxicity or progression), with an approximate duration of 2 years. (NCT02783300)
Latest
news: * On September 15, 2016, Epizyme announced it has earned a $6 million milestone payment from GSK. The milestone payment follows GSK's initiation of patient dosing in a Phase 1 clinical trial of GSK3326595 (formerly EPZ015938), a first-in-class protein arginine methyltransferase-5 (PRMT5) inhibitor discovered by Epizyme and licensed to GSK.
