FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308406723> ?p ?o ?g. }

• W4308406723 abstract "<h3>Background</h3> Cancer immunotherapies target immune checkpoints and have been transformative in the treatment practices of oncology. However, only a subset of all patients in most cancer types effectively respond to these therapies. It has been established that approximately 60% to 70% of patients who receive anti–programmed cell death protein-1 (anti–PD-1) or anti-cytotoxic T-lymphocyte–associated antigen 4 (CTLA4) do not respond to treatment.¹ Furthermore, acquired resistance is common, causing some patients who initially responded to the therapy to later experience disease progression. Therefore, there is a significant opportunity for immunotherapy expansion in cancer treatment. Diacylglycerol kinase (DGK) is a large enzyme family of 10 mammalian isoenzymes that catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). In T cells, DGK (such as DGKζ) inhibits DAG-mediated signals following T-cell receptor engagement by catalyzing the conversion of DAG to PA.² Even when PD-1 is blocked by anti–PD-1 antibodies, there may be partial inactivation by DGK. Therefore, DGK inhibitors have the potential to enhance DAG downstream signaling, leading to T-cell activation regardless of the PD-1 signal. ASP1570 is a novel inhibitor against DGKζ and has the potential to enhance DAG downstream signaling which can activate T cells regardless of PD-1 signaling and lead to tumor killing. ASP1570 restored T-cell functions suppressed by multiple immunosuppressive signals (PD-1, transforming growth factor beta, prostaglandin E2, and adenosine) and induced tumor growth inhibition in mice models of MC38 (anti-PD1 sensitive) and B16-F1 (tumor-infiltrating lymphocyte poor, anti–PD-1 insensitive). Taken together, ASP1570 treatment as a single agent and/or in combination with anti–PD-1 therapy for locally advanced or metastatic solid tumors may result in clinical benefit. <h3>Methods</h3> This is a phase 1/2, open-label, multicenter, multiple-dose, dose-escalation/expansion study of ASP1570 in participants with locally advanced or metastatic solid tumors. The study will enroll approximately 168 participants into 2 phases, dose escalation and dose expansion, to assess safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics (figure 1). The study will consist of the following periods: screening, treatment with ASP1570 daily oral dosing in 21-day cycles, end of treatment, follow-up (safety and survival follow-up), and end of study (figure 2). The study is open for enrollment. <h3>Acknowledgements</h3> We thank the patients, investigators, and study teams for being involved in this study. Editorial support was provided by OPEN Health and funded by Astellas Pharma, Inc. This study is funded by Astellas Pharma, Inc. <h3>Trial Registration</h3> NCT05083481 <h3>References</h3> Simeone E, Ascierto PA. Anti-PD-1 and PD-L1 antibodies in metastatic melanoma. <i>Melanoma Manag</i>. 2017;<b>4</b>:175–178. Zhong XP, Guo R, Zhou H, Liu C, Wan CK. Diacylglycerol kinases in immune cell function and self-tolerance. <i>Immunol Rev</i>. 2008;<b>224</b>:249–264. <h3>Ethics Approval</h3> This study received IRB approval from Advarra (Pro00055357), and all participants must provide informed consent before taking part. <h3>Consent</h3> Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal." @default.
• W4308406723 created "2022-11-11" @default.
• W4308406723 creator A5009999197 @default.
• W4308406723 creator A5016734554 @default.
• W4308406723 creator A5022682916 @default.
• W4308406723 creator A5022951710 @default.
• W4308406723 creator A5033349344 @default.
• W4308406723 creator A5036587861 @default.
• W4308406723 creator A5044413567 @default.
• W4308406723 creator A5055214556 @default.
• W4308406723 creator A5055353034 @default.
• W4308406723 creator A5055954903 @default.
• W4308406723 creator A5061833849 @default.
• W4308406723 creator A5063337705 @default.
• W4308406723 creator A5068324675 @default.
• W4308406723 creator A5072492344 @default.
• W4308406723 creator A5079085880 @default.
• W4308406723 creator A5086722574 @default.
• W4308406723 date "2022-11-01" @default.
• W4308406723 modified "2023-10-16" @default.
• W4308406723 title "754 A phase 1/2 study of ASP1570 in participants with locally advanced or metastatic solid tumors who have progressed on, or are ineligible for, all available standard therapies" @default.
• W4308406723 doi "https://doi.org/10.1136/jitc-2022-sitc2022.0754" @default.
• W4308406723 hasPublicationYear "2022" @default.
• W4308406723 type Work @default.
• W4308406723 citedByCount "0" @default.
• W4308406723 crossrefType "proceedings-article" @default.
• W4308406723 hasAuthorship W4308406723A5009999197 @default.
• W4308406723 hasAuthorship W4308406723A5016734554 @default.
• W4308406723 hasAuthorship W4308406723A5022682916 @default.
• W4308406723 hasAuthorship W4308406723A5022951710 @default.
• W4308406723 hasAuthorship W4308406723A5033349344 @default.
• W4308406723 hasAuthorship W4308406723A5036587861 @default.
• W4308406723 hasAuthorship W4308406723A5044413567 @default.
• W4308406723 hasAuthorship W4308406723A5055214556 @default.
• W4308406723 hasAuthorship W4308406723A5055353034 @default.
• W4308406723 hasAuthorship W4308406723A5055954903 @default.
• W4308406723 hasAuthorship W4308406723A5061833849 @default.
• W4308406723 hasAuthorship W4308406723A5063337705 @default.
• W4308406723 hasAuthorship W4308406723A5068324675 @default.
• W4308406723 hasAuthorship W4308406723A5072492344 @default.
• W4308406723 hasAuthorship W4308406723A5079085880 @default.
• W4308406723 hasAuthorship W4308406723A5086722574 @default.
• W4308406723 hasBestOaLocation W43084067231 @default.
• W4308406723 hasConcept C121608353 @default.
• W4308406723 hasConcept C126322002 @default.
• W4308406723 hasConcept C154317977 @default.
• W4308406723 hasConcept C195794163 @default.
• W4308406723 hasConcept C202751555 @default.
• W4308406723 hasConcept C203014093 @default.
• W4308406723 hasConcept C2776090121 @default.
• W4308406723 hasConcept C2776909261 @default.
• W4308406723 hasConcept C2777701055 @default.
• W4308406723 hasConcept C2778918659 @default.
• W4308406723 hasConcept C2780674031 @default.
• W4308406723 hasConcept C36020004 @default.
• W4308406723 hasConcept C41625074 @default.
• W4308406723 hasConcept C502942594 @default.
• W4308406723 hasConcept C55493867 @default.
• W4308406723 hasConcept C62478195 @default.
• W4308406723 hasConcept C71924100 @default.
• W4308406723 hasConcept C86803240 @default.
• W4308406723 hasConcept C8891405 @default.
• W4308406723 hasConcept C95444343 @default.
• W4308406723 hasConcept C96232424 @default.
• W4308406723 hasConceptScore W4308406723C121608353 @default.
• W4308406723 hasConceptScore W4308406723C126322002 @default.
• W4308406723 hasConceptScore W4308406723C154317977 @default.
• W4308406723 hasConceptScore W4308406723C195794163 @default.
• W4308406723 hasConceptScore W4308406723C202751555 @default.
• W4308406723 hasConceptScore W4308406723C203014093 @default.
• W4308406723 hasConceptScore W4308406723C2776090121 @default.
• W4308406723 hasConceptScore W4308406723C2776909261 @default.
• W4308406723 hasConceptScore W4308406723C2777701055 @default.
• W4308406723 hasConceptScore W4308406723C2778918659 @default.
• W4308406723 hasConceptScore W4308406723C2780674031 @default.
• W4308406723 hasConceptScore W4308406723C36020004 @default.
• W4308406723 hasConceptScore W4308406723C41625074 @default.
• W4308406723 hasConceptScore W4308406723C502942594 @default.
• W4308406723 hasConceptScore W4308406723C55493867 @default.
• W4308406723 hasConceptScore W4308406723C62478195 @default.
• W4308406723 hasConceptScore W4308406723C71924100 @default.
• W4308406723 hasConceptScore W4308406723C86803240 @default.
• W4308406723 hasConceptScore W4308406723C8891405 @default.
• W4308406723 hasConceptScore W4308406723C95444343 @default.
• W4308406723 hasConceptScore W4308406723C96232424 @default.
• W4308406723 hasLocation W43084067231 @default.
• W4308406723 hasOpenAccess W4308406723 @default.
• W4308406723 hasPrimaryLocation W43084067231 @default.
• W4308406723 hasRelatedWork W2318621576 @default.
• W4308406723 hasRelatedWork W2763883091 @default.
• W4308406723 hasRelatedWork W2937326325 @default.
• W4308406723 hasRelatedWork W2979186475 @default.
• W4308406723 hasRelatedWork W3180780036 @default.
• W4308406723 hasRelatedWork W3217412908 @default.
• W4308406723 hasRelatedWork W4220665865 @default.
• W4308406723 hasRelatedWork W4291367166 @default.
• W4308406723 hasRelatedWork W4360983034 @default.
• W4308406723 hasRelatedWork W4366393479 @default.
• W4308406723 isParatext "false" @default.
• W4308406723 isRetracted "false" @default.

• next