FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2992583613> ?p ?o ?g. }

• W2992583613 endingPage "C066" @default.
• W2992583613 startingPage "C066" @default.
• W2992583613 abstract "Abstract BT5528 is a Bicycle Toxin Conjugate (BTC) in which an EphA2 binding peptide (a Bicycle®) is conjugated through an inert sarcosine spacer chain, and a cleavable linker, to the antimitotic toxin MMAE. Increased EphA2 expression has been reported in multiple tumor types (including NSCLC, ovarian cancer, TNBC, gastric/upper GI, pancreatic and urothelial cancers) and so represents a attractive tumor binding target. The identification, characterization and initial in vivo profiling of BT5528 has previously been described. This abstract describes a more detailed analysis of the mechanism of action of BT5528. Dosing of BT5528 on a once weekly schedule is efficacious in a range of tumour models. Observed anti-tumor activity is closely related to the level of EphA2 expression on tumor cells ranging from complete responses in EphA2 positive models to minimal activity in EphA2 low/null models. Efficacy of BT5528 is also seen in a number of “hard to hit” models including large (~1000mm3) patient derived xenograft models (PDX) including highly-resistant models and PDX models of pancreatic ductal adenocarcinoma. We also demonstrate the utility of BT5528 in disseminated disease in an EphA2 positive model of bone metastasis. Efficacy of BT5528 is seen even when dosed as infrequently as every 2 weeks and is not dependent on infusion duration allowing for flexible drug administration schedule. Additionally, we demonstrate the significance of the BT5528 bystander effect to anti-tumor activity using versions of BT5528 with non-releasable payload as well as non-cell permeable payload. Efficacy of BT5528 is also seen in a number of “hard to hit” models including large (~1000mm3) PDX, highly-resistant models, models of pancreatic cancer, and models of metastatic disease. Importantly, BT5528 can produce this profound efficacy without the bleeding and coagulation toxicity seen with previous ADC approaches to this target. The overall profile of BT5528 provides a highly differentiated approach to targeting EphA2, offering the potential for profound efficacy in a range of solid tumours. IND-enabling activities are underway, with clinical trials expected to start later this year. Citation Format: Gavin Bennett, Amy Brown, Gemma Mudd, Johanna Lahdenranta, Nicholas Keen. BT5528, a Bicycle Toxin Conjugate targeting EphA2: mechanism of action and clinical translation [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C066. doi:10.1158/1535-7163.TARG-19-C066" @default.
• W2992583613 created "2019-12-13" @default.
• W2992583613 creator A5008228016 @default.
• W2992583613 creator A5008373586 @default.
• W2992583613 creator A5045177125 @default.
• W2992583613 creator A5057024955 @default.
• W2992583613 creator A5078331109 @default.
• W2992583613 date "2019-12-01" @default.
• W2992583613 modified "2023-10-16" @default.
• W2992583613 title "Abstract C066: BT5528, a Bicycle Toxin Conjugate targeting EphA2: mechanism of action and clinical translation" @default.
• W2992583613 doi "https://doi.org/10.1158/1535-7163.targ-19-c066" @default.
• W2992583613 hasPublicationYear "2019" @default.
• W2992583613 type Work @default.
• W2992583613 sameAs 2992583613 @default.
• W2992583613 citedByCount "1" @default.
• W2992583613 countsByYear W29925836132023 @default.
• W2992583613 crossrefType "journal-article" @default.
• W2992583613 hasAuthorship W2992583613A5008228016 @default.
• W2992583613 hasAuthorship W2992583613A5008373586 @default.
• W2992583613 hasAuthorship W2992583613A5045177125 @default.
• W2992583613 hasAuthorship W2992583613A5057024955 @default.
• W2992583613 hasAuthorship W2992583613A5078331109 @default.
• W2992583613 hasConcept C101544691 @default.
• W2992583613 hasConcept C121608353 @default.
• W2992583613 hasConcept C126322002 @default.
• W2992583613 hasConcept C134306372 @default.
• W2992583613 hasConcept C150582083 @default.
• W2992583613 hasConcept C150903083 @default.
• W2992583613 hasConcept C170493617 @default.
• W2992583613 hasConcept C197336794 @default.
• W2992583613 hasConcept C207001950 @default.
• W2992583613 hasConcept C2779013556 @default.
• W2992583613 hasConcept C2780210213 @default.
• W2992583613 hasConcept C33923547 @default.
• W2992583613 hasConcept C502942594 @default.
• W2992583613 hasConcept C71924100 @default.
• W2992583613 hasConcept C86803240 @default.
• W2992583613 hasConcept C98274493 @default.
• W2992583613 hasConceptScore W2992583613C101544691 @default.
• W2992583613 hasConceptScore W2992583613C121608353 @default.
• W2992583613 hasConceptScore W2992583613C126322002 @default.
• W2992583613 hasConceptScore W2992583613C134306372 @default.
• W2992583613 hasConceptScore W2992583613C150582083 @default.
• W2992583613 hasConceptScore W2992583613C150903083 @default.
• W2992583613 hasConceptScore W2992583613C170493617 @default.
• W2992583613 hasConceptScore W2992583613C197336794 @default.
• W2992583613 hasConceptScore W2992583613C207001950 @default.
• W2992583613 hasConceptScore W2992583613C2779013556 @default.
• W2992583613 hasConceptScore W2992583613C2780210213 @default.
• W2992583613 hasConceptScore W2992583613C33923547 @default.
• W2992583613 hasConceptScore W2992583613C502942594 @default.
• W2992583613 hasConceptScore W2992583613C71924100 @default.
• W2992583613 hasConceptScore W2992583613C86803240 @default.
• W2992583613 hasConceptScore W2992583613C98274493 @default.
• W2992583613 hasIssue "12_Supplement" @default.
• W2992583613 hasLocation W29925836131 @default.
• W2992583613 hasOpenAccess W2992583613 @default.
• W2992583613 hasPrimaryLocation W29925836131 @default.
• W2992583613 hasRelatedWork W2337680646 @default.
• W2992583613 hasRelatedWork W2346074809 @default.
• W2992583613 hasRelatedWork W2397227313 @default.
• W2992583613 hasRelatedWork W2460428725 @default.
• W2992583613 hasRelatedWork W2582912872 @default.
• W2992583613 hasRelatedWork W2728479436 @default.
• W2992583613 hasRelatedWork W3030400738 @default.
• W2992583613 hasRelatedWork W3104930108 @default.
• W2992583613 hasRelatedWork W4306156633 @default.
• W2992583613 hasRelatedWork W4311290603 @default.
• W2992583613 hasVolume "18" @default.
• W2992583613 isParatext "false" @default.
• W2992583613 isRetracted "false" @default.
• W2992583613 magId "2992583613" @default.
• W2992583613 workType "article" @default.