ArticleTherapeutic advances in hematology2024
Phase I/II study of the clinical activity and safety of GSK3326595 in patients with myeloid neoplasms.
Article in Therapeutic advances in hematology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03614728 (A Phase I/II Study to Investigate the Safety and Clinical Activity of GSK3326595 and Other Agents in Participants With Myelodysplastic Syndrome and Acute Myeloid Leukaemia), which is not on this map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I/II Study to Investigate the Safety and Clinical Activity of GSK3326595 and Other Agents in Participants With Myelodysplastic Syndrome and Acute Myeloid Leukaemia
Who cites it
26 citing papers in PubMed.
- Systemic administration of the PRMT5 inhibitor GSK3326595 does not induce overt cardiotoxicity in the murine heart.Journal of molecular and cellular cardiology plus · 2026Article
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Targeting PRMTs with small-molecule inhibitors: a comprehensive review.RSC medicinal chemistry · 2026Review
- Article
- PRMT5 as a Key Driver of Stemness and Metastatic Potential in Triple-Negative Breast Cancer.Biomolecules · 2026Review
- Splicing factor mutations clearance and outcomes in clonal myeloid neoplasms: a referral center experience.Annals of hematology · 2026Article
- Targeting PRMTs Creates Vulnerability of DNA Double-Stand Break Repair Pathways, and Potentiates Chemotherapy Efficacy in TNBC.Cancer science · 2026Article
- MTAP Deletion in Oncogenesis: A Synthetic Lethality Scenario.Cancer research · 2026Review
- PRMT5 is Frequently Upregulated and a Potential Therapeutic Target in MTAP-deficient Malignant Peripheral Nerve Sheath Tumors.bioRxiv : the preprint server for biology · 2026Article
- Fusion oncoproteins orchestrate tumorigenesis and sustain malignant progression via a positive feedback mechanism.Cell & bioscience · 2026Review
- Interferon-Driven Biomarkers and Synergistic Therapy for PRMT5 Inhibition in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RNA Splicing as a Therapeutic Target in Cancer.Annual review of pharmacology and toxicology · 2026Review
- Review
- Cracking PRMT5: Mechanistic insights, clinical advances, and AI-driven strategies.Cancer letters · 2025Review
- Arginine methylation in cancer: mechanisms and therapeutic implications.Biomarker research · 2025Review
- Biomolecular condensates: molecular structure, biological functions, diseases, and therapeutic targets.Molecular biomedicine · 2025Review
- Splicing Factor Mutations in Chronic Myelomonocytic Leukemia: Biological Consequences and Therapeutic Implications.Current hematologic malignancy reports · 2025Review
- The role of ASXL1, SRSF2, and EZH2 mutations in chromatin dysregulation of myelodysplastic neoplasia and acute myeloid leukemia.Leukemia · 2025Review
- Therapeutic targeting of protein arginine methyltransferases reduces breast cancer progression by disrupting angiogenic pathways.Biochemistry and biophysics reports · 2025Review
- Review
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: 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. Objectives: To determine the clinical activity, safety, tolerability, dosing, additional measures of clinical activity, pharmacokinetics, and pharmacodynamics of GSK3326595. Design: 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. Methods: 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. Results: 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 wild-type. Frequent GSK3326595-related AEs were decreased platelet count (27%), dysgeusia (23%), fatigue (20%), and nausea (20%). GSK3326595 had rapid absorption, with a Conclusion: 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. Trial registration: ClinicalTrials.gov: NCT03614728.
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