Matches in SemOpenAlex for { <https://semopenalex.org/work/W2892022219> ?p ?o ?g. }
Showing items 1 to 81 of
81
with 100 items per page.
- W2892022219 endingPage "TPS3627" @default.
- W2892022219 startingPage "TPS3627" @default.
- W2892022219 abstract "TPS3627 Background: Mutant KRAS tumors show a dependency on WT-H/N-Ras for activation of ATR/Chk1-mediated G2 DNA damage response (Grabocka, Cell, 2015). We have shown in vitro that the Wee1 kinase inhibitor AZD1775, which acts to abrogate the G2 DNA damage checkpoint and induces replication stress during S-phase, selectively sensitizes RAS/RAF mutant cells to the DNA damaging agent irinotecan. Up to 65% of metastatic colorectal cancers harbor RAS or BRAF mutations and these patients have limited treatment options following first line therapy. Methods: This is an open label, single-arm, phase Ib study using a modified 3+3 dose-escalation schedule with expansion cohort. Primary objective is to determine the MTD of AZD1775 in combination with irinotecan as 2 nd -line therapy in patients with metastatic KRAS, NRAS or BRAF mutated colorectal cancer. Up to 18 patients will be enrolled in the dose escalation portion. Standard dose irinotecan is given on day 1 of every 2 week cycle. AZD1775 is administered PO twice daily for 3 to 5 days of each cycle, starting cycle 2. The maximum tolerated dose (MTD) is defined as the highest dose level at which ≤1 of 6 patients experience a dose limiting toxicity. Once the MTD is reached and/or recommended dose for expansion is determined, a dose expansion cohort of 14 patients will be enrolled. Secondary endpoints include characterizing the safety profile at the MTD, obtaining a preliminary estimate of efficacy for the combination (measured by overall response rate, progression-free and overall survival rates), and obtaining pharmacokinetic parameters. Pre- and on-treatment biopsies will be collected from the expansion cohort to determine: adequate target engagement of Wee1, changes in markers of DNA damage, TP53 mutation status, and changes in gene expression profiles in order to identify potential biomarkers of response. At February 2017, 2 patients have been enrolled on this study. Clinical trial information: NCT02906059. [Table: see text]" @default.
- W2892022219 created "2018-09-27" @default.
- W2892022219 creator A5002311881 @default.
- W2892022219 creator A5007711795 @default.
- W2892022219 creator A5017215021 @default.
- W2892022219 creator A5048973199 @default.
- W2892022219 creator A5056698491 @default.
- W2892022219 date "2017-05-20" @default.
- W2892022219 modified "2023-10-17" @default.
- W2892022219 title "A phase Ib study combining irinotecan with AZD1775, a selective WEE 1 kinase inhibitor, in RAS/RAF mutated metastatic colorectal cancer patients who progressed on first line therapy." @default.
- W2892022219 doi "https://doi.org/10.1200/jco.2017.35.15_suppl.tps3627" @default.
- W2892022219 hasPublicationYear "2017" @default.
- W2892022219 type Work @default.
- W2892022219 sameAs 2892022219 @default.
- W2892022219 citedByCount "3" @default.
- W2892022219 countsByYear W28920222192019 @default.
- W2892022219 countsByYear W28920222192021 @default.
- W2892022219 countsByYear W28920222192022 @default.
- W2892022219 crossrefType "journal-article" @default.
- W2892022219 hasAuthorship W2892022219A5002311881 @default.
- W2892022219 hasAuthorship W2892022219A5007711795 @default.
- W2892022219 hasAuthorship W2892022219A5017215021 @default.
- W2892022219 hasAuthorship W2892022219A5048973199 @default.
- W2892022219 hasAuthorship W2892022219A5056698491 @default.
- W2892022219 hasConcept C105696609 @default.
- W2892022219 hasConcept C120504264 @default.
- W2892022219 hasConcept C121608353 @default.
- W2892022219 hasConcept C126322002 @default.
- W2892022219 hasConcept C143998085 @default.
- W2892022219 hasConcept C21790070 @default.
- W2892022219 hasConcept C2775930923 @default.
- W2892022219 hasConcept C2779744173 @default.
- W2892022219 hasConcept C2780258809 @default.
- W2892022219 hasConcept C2780259306 @default.
- W2892022219 hasConcept C2781187634 @default.
- W2892022219 hasConcept C2781252693 @default.
- W2892022219 hasConcept C29537977 @default.
- W2892022219 hasConcept C50001416 @default.
- W2892022219 hasConcept C502942594 @default.
- W2892022219 hasConcept C526805850 @default.
- W2892022219 hasConcept C530470458 @default.
- W2892022219 hasConcept C71924100 @default.
- W2892022219 hasConceptScore W2892022219C105696609 @default.
- W2892022219 hasConceptScore W2892022219C120504264 @default.
- W2892022219 hasConceptScore W2892022219C121608353 @default.
- W2892022219 hasConceptScore W2892022219C126322002 @default.
- W2892022219 hasConceptScore W2892022219C143998085 @default.
- W2892022219 hasConceptScore W2892022219C21790070 @default.
- W2892022219 hasConceptScore W2892022219C2775930923 @default.
- W2892022219 hasConceptScore W2892022219C2779744173 @default.
- W2892022219 hasConceptScore W2892022219C2780258809 @default.
- W2892022219 hasConceptScore W2892022219C2780259306 @default.
- W2892022219 hasConceptScore W2892022219C2781187634 @default.
- W2892022219 hasConceptScore W2892022219C2781252693 @default.
- W2892022219 hasConceptScore W2892022219C29537977 @default.
- W2892022219 hasConceptScore W2892022219C50001416 @default.
- W2892022219 hasConceptScore W2892022219C502942594 @default.
- W2892022219 hasConceptScore W2892022219C526805850 @default.
- W2892022219 hasConceptScore W2892022219C530470458 @default.
- W2892022219 hasConceptScore W2892022219C71924100 @default.
- W2892022219 hasIssue "15_suppl" @default.
- W2892022219 hasLocation W28920222191 @default.
- W2892022219 hasOpenAccess W2892022219 @default.
- W2892022219 hasPrimaryLocation W28920222191 @default.
- W2892022219 hasRelatedWork W1996349887 @default.
- W2892022219 hasRelatedWork W2010163599 @default.
- W2892022219 hasRelatedWork W2132451283 @default.
- W2892022219 hasRelatedWork W2140327757 @default.
- W2892022219 hasRelatedWork W2286973448 @default.
- W2892022219 hasRelatedWork W2435704186 @default.
- W2892022219 hasRelatedWork W2590132612 @default.
- W2892022219 hasRelatedWork W2984714837 @default.
- W2892022219 hasRelatedWork W3000288349 @default.
- W2892022219 hasRelatedWork W3040911471 @default.
- W2892022219 hasVolume "35" @default.
- W2892022219 isParatext "false" @default.
- W2892022219 isRetracted "false" @default.
- W2892022219 magId "2892022219" @default.
- W2892022219 workType "article" @default.