“Study to Investigate the Safety and Clinical Activity of GSK3326595 and Other Agents to Treat Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukaemia (AML)”
GSK3326595 is a potent, selective, reversible inhibitor of the protein arginine methyltransferase 5 (PRMT5)/Methylosome protein 50 (MEP50) complex that is being tested as an oral treatment for human subjects with cancer. Myelodysplastic syndrome and acute myeloid leukaemia are bone marrow neoplasms for which novel, effective therapies are desperately needed. This is an open-label, multicentre, multi-part study to evaluate the safety, tolerability, and clinical activity of GSK3326595 in subjects with relapsed and refractory MDS, chronic myelomonocytic leukaemia (CMML), and hypoproliferative AML that has evolved from an antecedent MDS. The study will be conducted in two parts and at the end of Part 1, if pre-specified criteria are met, then the study will be expanded with three additional parts that will be opened in parallel (Part 2A, 2B and 2C). Part 1 is composed of a single-arm dose expansion cohort to determine the clinical benefit rate of GSK3326595. Part 2A is a randomized head-to-head Phase II evaluation of GSK3326595 compared to investigator's choice of best available care (BAC). Part 2B is composed of an abbreviated series of dose escalation cohorts followed by a single-arm dose expansion cohort to determine the overall response rate of the combination of GSK3326595 plus 5-azaciditine in newly-diagnosed MDS. Part 2C is a single-arm dose expansion study to evaluate the clinical activity of single-agent GSK3326595 in subjects with AML whose disease contains mutations in spliceosome proteins.
Drug - GSK3326595
GSK3326595 is available as 25 and 100 mg strengths as free-base drug substance to be administered orally with water with no food or antacids for 1 hour before and 2 hour after each dose.
Drug - 5-azacitidine
5-azacitidine is available as Lyophilized powder in 100 mg single-dose vials administered 75 mg/m2 subcutaneously or intravenously for 7 days out of a 28 day cycle, as per local standard.
Drug - Best available care
Best available care will be the treatment of choice as considered by the investigator.
A Phase I/II Study to Investigate the Safety and Clinical Activity of GSK3326595 and Other Agents in Subjects With Myelodysplastic Syndrome and Acute Myeloid Leukaemia