[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-331299-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-331299-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","phase-iii-study-of-the-clinical-activity-and-safety-of-gsk3326595-in-patients-with-myeloid-neoplasms","Phase I/II study of the clinical activity and safety of GSK3326595 in patients with myeloid neoplasms","","GSK3326595 is a selective, reversible PRMT5 inhibitor evaluated for treatment of myelodysplastic syndrome, chronic myelomonocytic leukemia, and acute myeloid leukemia. A phase I/II open-label, multicenter study assessed clinical activity, safety, tolerability, dosing, pharmacokinetics and pharmacodynamics in adults with relapsed/refractory disease receiving oral once-daily monotherapy. Clinical benefit was limited, with 5 of 30 patients meeting CBR criteria, including responses such as stable disease and complete marrow remission, alongside common AEs like thrombocytopenia, dysgeusia, fatigue, and nausea.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/phase-iii-study-of-the-clinical-activity-and-safety-of-gsk3326595-in-patients-with-myeloid-neoplasms/331299/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/phase-iii-study-of-the-clinical-activity-and-safety-of-gsk3326595-in-patients-with-myeloid-neoplasms/331299.png","ImageObject",300,407,{"name":42,"@type":43},"Levi","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",10,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the purpose of the Phase I/II study of GSK3326595?","Question",{"text":63,"@type":64},"The study evaluates clinical activity, safety, tolerability, dosing, and pharmacokinetics/pharmacodynamics of GSK3326595 in relapsed/refractory myeloid neoplasms. It also explores how spliceosome mutation profiles relate to clinical response.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How was clinical activity measured in the study?",{"text":68,"@type":64},"Clinical activity used the clinical benefit rate (CBR), defined by complete remission, complete marrow remission, partial remission, stable disease longer than 8 weeks, or hematologic improvement.",{"name":70,"@type":61,"acceptedAnswer":71},"What were the main safety findings and common adverse events?",{"text":72,"@type":64},"GSK3326595 showed a safety profile broadly consistent with other PRMT5 inhibitor studies. Frequent related adverse events included decreased platelet count, dysgeusia, fatigue, and nausea.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},331299,1790145107,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,111,115,120,123,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":108,"show_sort_weight":109,"slug":110},7,"Healthcare",40,"healthcare",{"id":112,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":113,"slug":114},8,30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":55,"slug":125},"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":112,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":109,"preview_page_count":4},7971461740909,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Phase I/II study of the clinical activity and safety of GSK3326595 in patients with myeloid neoplasms  \nJustin Watts, Mark D. Minden, Kimo Bachiashvili, Andrew M. Brunner, SameemAbedin, Timothy Crossman, Magdalena Zajac, Veronica Moroz, Jacqueline L. Egger, Aarti Tarkar, Brandon E. Kremer, Olena Barbash  \nand Gautam Borthakur  \nAbstract  \nBackground: GSK3326595 is a potent, selective, reversible protein arginine methyltransferase 5 (PRMT5) inhibitor under investigation for treatment of myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) . In preclinical models of AML, PRMT5 inhibition decreased proliferation and increased cell death, supporting additional clinical research in myeloid neoplasms.  \nObjectives: To determine the clinical activity, safety, tolerability, dosing, additional measures of clinical activity, pharmacokinetics, and pharmacodynamics of GSK3326595 .  \nDesign: In part 1 of this open-label, multicenter, multipart, phase I/II study, adults with relapsed/refractory myeloid neoplasms (e. g. , MDS, CMML, and AML) received monotherapy with 400 or 300 mg oral GSK3326595 once daily. Study termination occurred prior to part 2 enrollment.  \nMethods: Clinical activity was determined by the clinical benefit rate (CBR; proportion of patients achieving complete remission (CR), complete marrow remission (mCR), partial remission, stable disease (SD) >8 weeks, or hematologic improvement) . Adverse events (AEs) were assessed by incidence and severity. Exploratory examination of spliceosome mutations was performed to determine the relationship between genomic profiles and clinical response to GSK3326595 .  \nResults: Thirty patients with a median age of 73.5 years (range, 47–90) were enrolled; 13 (43%) and 17 (57%) received 400 and 300 mg of GSK3326595, respectively. Five (17%) patients met CBR criteria: 4 (13%) with SD >8 weeks and 1 (3%) achieving mCR. Of five patients with clinical benefit: three had SRSF2 mutation, one U2AF1, and one was splicing factor wildtype. Frequent GSK3326595-related AEs were decreased platelet count (27%), dysgeusia (23%), fatigue (20%), and nausea (20%) . GSK3326595 had rapid absorption, with a Tmax of approximately 2 h and a terminal half-life of 4–6 h.  \nConclusion: GSK3326595 monotherapy had limited clinical activity in heavily pretreated patients despite robust target engagement. The safety profile was broadly consistent with other published PRMT5 inhibitor studies.  \nTrial registration: [ClinicalTrials.gov:](ClinicalTrials.gov:) NCT03614728.  \nPlain language summary  \nA clinical study to determine the effectiveness and safety of a medication called GSK3326595 in patients with cancers that affect the blood and bone marrow  \nWhat is this study about? This summary provides the results of a study performed to see how safe and effective treatment with a once daily, oral medication called GSK3326595 was in patients with blood and bone marrow cancers.  \nTherAdv Hematol 2024, Vol. 15: 1–16  \nDOI: 10. 1177/  \n20406207241275376 © The Author(s), 2024. Article reuse guidelines:  \n[sagepub.com/journals](sagepub.com/journals)permissions  \nCorrespondence to:  \nTimothy Crossman  \nOncology Clinical Development, GSK, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK  \ntimothy.r.crossman@ [gsk.com](gsk.com)  \nJustin Watts  \nDivision of Hematology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA  \nMark D. Minden  \nDepartment of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada  \nKimo Bachiashvili  \nDivision of Hematology and Oncology, O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA  \nAndrew M. Brunner  \nLeukemia Program, Massachusetts General Hospital Cancer Center, Boston, MA, USA  \nSameem Abedin  \nDivision of Hematology/ Oncology, Medical College of Wisconsin, Milwaukee, WI, USA  \nMagdalena Zajac Jacqueline L. Egger  \nOncology Cl","cbCaibpc4AmZKqzZ","https://ap.wps.com/l/cbCaibpc4AmZKqzZ","pdf",712256,16,"English","# Background and objectives\n## Study design and methods\n## Results and conclusions","[{\"question\":\"What is the purpose of the Phase I/II study of GSK3326595?\",\"answer\":\"The study evaluates clinical activity, safety, tolerability, dosing, and pharmacokinetics/pharmacodynamics of GSK3326595 in relapsed/refractory myeloid neoplasms. It also explores how spliceosome mutation profiles relate to clinical response.\"},{\"question\":\"How was clinical activity measured in the study?\",\"answer\":\"Clinical activity used the clinical benefit rate (CBR), defined by complete remission, complete marrow remission, partial remission, stable disease longer than 8 weeks, or hematologic improvement.\"},{\"question\":\"What were the main safety findings and common adverse events?\",\"answer\":\"GSK3326595 showed a safety profile broadly consistent with other PRMT5 inhibitor studies. Frequent related adverse events included decreased platelet count, dysgeusia, fatigue, and nausea.\"}]","Phase I/II study of the clinical activity and safety of GSK3326595 in patients with myeloid neoplasms | PDF",1789992579]