FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4385655001> ?p ?o ?g. }

• W4385655001 endingPage "e451088e" @default.
• W4385655001 startingPage "e451088e" @default.
• W4385655001 abstract "Topic: 4. Acute myeloid leukemia - Clinical Background: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are hematologic malignancies originating from immature myeloid progenitor cells within the bone marrow. Depending on age and genetic disposition, approximately 40%-60% of patients may have disease that is refractory to primary treatment, and of those who achieve initial complete response, over 40% will experience relapse. In the relapsed/refractory setting, median survival is inadequate, which highlights an unmet medical need. Within the cGAS-STING-TBK1 pathway, stimulator of interferon genes (STING) is the main adaptor molecule as it modulates the sensing of cytosolic DNA. STING activation mediates the generation of type I interferons (IFNα and IFNβ) and pro-inflammatory cytokines, drivers of T-cell–dependent antitumor immunity. In preclinical studies, STING agonists have also shown direct cytotoxic activity against AML cells in addition to their immune stimulatory activity. Compared with other tumor types, STING is expressed at a higher level in AML cells (The Cancer Genome Atlas, National Cancer Institute), which may explain the observed cytotoxicity upon STING activation (Gulen MF, et al. Nat Commun 2017.8:427). The high level of STING expression combined with preclinical evidence of antitumor activity makes AML an appropriate malignancy in which to determine proof of mechanism and investigate the clinical activity of GSK3745417, a novel STING agonist that has so far only been studied in solid tumors. Aims: The primary objectives are to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and cytotoxicity of intravenously administered GSK3745417 in patients with relapsed or refractory AML or high-/very high-risk MDS. Methods: This is a first-in-clinic, phase 1, dose escalation (part 1) and dose expansion (part 2) study. Key eligibility criteria include patients who are 18 to 75 years of age with a diagnosis of relapsed or refractory AML (World Health Organization criteria) or high-/very high-risk MDS (Revised International Prognostic Scoring System) that has relapsed after or was refractory to prior therapy with a hypomethylating agent. Enrolment in part 1 dose escalation is ongoing, which comprises intrapatient dose escalation within cohorts to define a cohort-level maximum tolerated dose. Dosing in part 1 will consist of 3 initial induction cycles of GSK3745417 followed by a maintenance schedule. Part 2 includes an expansion cohort receiving the recommended induction regimen from part 1, followed by maintenance dose escalation. In total, approximately 72 patients will be enrolled: 22 patients in part 1 and 50 patients in part 2. Peripheral blood and bone marrow sampling will permit response assessment and biomarker analysis to elucidate the mechanism of GSK3745417 activity in AML and MDS. Results: Data for the primary endpoint are expected by the end of 2025. Summary/Conclusion: Accrual is ongoing. Clinical trial information: NCT05424380. Keywords: Acute myeloid leukemia, Clinical trial, MDS, MDS/AML" @default.
• W4385655001 created "2023-08-09" @default.
• W4385655001 creator A5000843085 @default.
• W4385655001 creator A5003559517 @default.
• W4385655001 creator A5003682435 @default.
• W4385655001 creator A5014347899 @default.
• W4385655001 creator A5016506303 @default.
• W4385655001 creator A5025508110 @default.
• W4385655001 creator A5026359397 @default.
• W4385655001 creator A5030174132 @default.
• W4385655001 creator A5036068419 @default.
• W4385655001 creator A5053069175 @default.
• W4385655001 creator A5055906478 @default.
• W4385655001 creator A5065647464 @default.
• W4385655001 creator A5070767391 @default.
• W4385655001 creator A5080931970 @default.
• W4385655001 creator A5086904406 @default.
• W4385655001 creator A5092611878 @default.
• W4385655001 date "2023-08-01" @default.
• W4385655001 modified "2023-10-16" @default.
• W4385655001 title "PB1887: STING AGONIST FOR THE TREATMENT OF RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA AND HIGH-RISK MYELODYSPLASTIC SYNDROME: A FIRST-IN-CLINIC PHASE 1 STUDY OF GSK3745417" @default.
• W4385655001 doi "https://doi.org/10.1097/01.hs9.0000974372.45108.8e" @default.
• W4385655001 hasPublicationYear "2023" @default.
• W4385655001 type Work @default.
• W4385655001 citedByCount "0" @default.
• W4385655001 crossrefType "journal-article" @default.
• W4385655001 hasAuthorship W4385655001A5000843085 @default.
• W4385655001 hasAuthorship W4385655001A5003559517 @default.
• W4385655001 hasAuthorship W4385655001A5003682435 @default.
• W4385655001 hasAuthorship W4385655001A5014347899 @default.
• W4385655001 hasAuthorship W4385655001A5016506303 @default.
• W4385655001 hasAuthorship W4385655001A5025508110 @default.
• W4385655001 hasAuthorship W4385655001A5026359397 @default.
• W4385655001 hasAuthorship W4385655001A5030174132 @default.
• W4385655001 hasAuthorship W4385655001A5036068419 @default.
• W4385655001 hasAuthorship W4385655001A5053069175 @default.
• W4385655001 hasAuthorship W4385655001A5055906478 @default.
• W4385655001 hasAuthorship W4385655001A5065647464 @default.
• W4385655001 hasAuthorship W4385655001A5070767391 @default.
• W4385655001 hasAuthorship W4385655001A5080931970 @default.
• W4385655001 hasAuthorship W4385655001A5086904406 @default.
• W4385655001 hasAuthorship W4385655001A5092611878 @default.
• W4385655001 hasBestOaLocation W43856550011 @default.
• W4385655001 hasConcept C104317684 @default.
• W4385655001 hasConcept C126322002 @default.
• W4385655001 hasConcept C127413603 @default.
• W4385655001 hasConcept C136449434 @default.
• W4385655001 hasConcept C143998085 @default.
• W4385655001 hasConcept C146978453 @default.
• W4385655001 hasConcept C150194340 @default.
• W4385655001 hasConcept C190727270 @default.
• W4385655001 hasConcept C197934379 @default.
• W4385655001 hasConcept C203014093 @default.
• W4385655001 hasConcept C2776239401 @default.
• W4385655001 hasConcept C2777349159 @default.
• W4385655001 hasConcept C2778375690 @default.
• W4385655001 hasConcept C2778461978 @default.
• W4385655001 hasConcept C2778729363 @default.
• W4385655001 hasConcept C2779300339 @default.
• W4385655001 hasConcept C2780007613 @default.
• W4385655001 hasConcept C2780817109 @default.
• W4385655001 hasConcept C502942594 @default.
• W4385655001 hasConcept C55493867 @default.
• W4385655001 hasConcept C71924100 @default.
• W4385655001 hasConcept C86803240 @default.
• W4385655001 hasConcept C8891405 @default.
• W4385655001 hasConcept C98274493 @default.
• W4385655001 hasConceptScore W4385655001C104317684 @default.
• W4385655001 hasConceptScore W4385655001C126322002 @default.
• W4385655001 hasConceptScore W4385655001C127413603 @default.
• W4385655001 hasConceptScore W4385655001C136449434 @default.
• W4385655001 hasConceptScore W4385655001C143998085 @default.
• W4385655001 hasConceptScore W4385655001C146978453 @default.
• W4385655001 hasConceptScore W4385655001C150194340 @default.
• W4385655001 hasConceptScore W4385655001C190727270 @default.
• W4385655001 hasConceptScore W4385655001C197934379 @default.
• W4385655001 hasConceptScore W4385655001C203014093 @default.
• W4385655001 hasConceptScore W4385655001C2776239401 @default.
• W4385655001 hasConceptScore W4385655001C2777349159 @default.
• W4385655001 hasConceptScore W4385655001C2778375690 @default.
• W4385655001 hasConceptScore W4385655001C2778461978 @default.
• W4385655001 hasConceptScore W4385655001C2778729363 @default.
• W4385655001 hasConceptScore W4385655001C2779300339 @default.
• W4385655001 hasConceptScore W4385655001C2780007613 @default.
• W4385655001 hasConceptScore W4385655001C2780817109 @default.
• W4385655001 hasConceptScore W4385655001C502942594 @default.
• W4385655001 hasConceptScore W4385655001C55493867 @default.
• W4385655001 hasConceptScore W4385655001C71924100 @default.
• W4385655001 hasConceptScore W4385655001C86803240 @default.
• W4385655001 hasConceptScore W4385655001C8891405 @default.
• W4385655001 hasConceptScore W4385655001C98274493 @default.
• W4385655001 hasIssue "S3" @default.
• W4385655001 hasLocation W43856550011 @default.
• W4385655001 hasLocation W43856550012 @default.
• W4385655001 hasOpenAccess W4385655001 @default.
• W4385655001 hasPrimaryLocation W43856550011 @default.
• W4385655001 hasRelatedWork W2005969440 @default.
• W4385655001 hasRelatedWork W2064760742 @default.

• next