FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4226068571> ?p ?o ?g. }

• W4226068571 endingPage "vi58" @default.
• W4226068571 startingPage "vi58" @default.
• W4226068571 abstract "Abstract CNS metastases are a prominent driver of cancer morbidity and mortality, especially as targeted therapies have improved systemic outcomes. Mutations in the ErbB/HER kinase family are known oncodrivers in many cancers. Extensive crosstalk among ErbB/HER receptors suggests that inhibition of multiple family members may benefit treatment and limit drug resistance. There is a desperate need for new agents that are more tolerable and effective in treating CNS metastases. EO1001 (APL-122) is a first-in-class, oral, irreversible pan-ErbB inhibitor targeting ErbB1, ErbB2 and ErbB4 with promising CNS penetration in preclinical models. Preclinical data suggests a favorable pharmacokinetic and safety profile and activity against ErbB-driven cancers in patient-derived xenograft models. We report on a first-in-human Phase 1-2 clinical trial in progress. Adult participants with confirmed ErbB-positive cancer, including patients with CNS involvement, who have progressed after standard-of-care, with adequate bone marrow, renal and liver function are eligible. ESCALATION: One subject per dose cohort is enrolled in an accelerated dose-escalation design until drug-related toxicity (≥G2) is observed in the first cycle, after which dose escalation will revert to a 3 + 3 design to determine the maximum tolerated dose (MTD). Cycle 1: Patients receive a single oral dose of EO1001 on day 1; single-dose pharmacokinetics are measured. Beginning on day 8, EO1001 is administered once daily for 21 days; multi-dose pharmacokinetics are measured. Cycles 2-6: EO1001 is administered once daily in continuous 28-day cycles for up to 20 weeks. EXPANSION: EO1001 will be administered once daily to 20 patients at the MTD in continuous 28-day cycles for up to 6 cycles to determine a recommended Phase 2 dose (RP2D) for further study. Toxicity is assessed based on NCI CTCAEv5 and tumor response is assessed by RECIST 1.1. CNS exposure is evaluated in patients via CSF collection with confirmed CNS disease involvement." @default.
• W4226068571 created "2022-05-05" @default.
• W4226068571 creator A5004569486 @default.
• W4226068571 creator A5010965225 @default.
• W4226068571 creator A5013583484 @default.
• W4226068571 creator A5014794937 @default.
• W4226068571 creator A5016462836 @default.
• W4226068571 creator A5020548821 @default.
• W4226068571 creator A5036712029 @default.
• W4226068571 creator A5049181098 @default.
• W4226068571 creator A5049351775 @default.
• W4226068571 creator A5050440486 @default.
• W4226068571 creator A5066896961 @default.
• W4226068571 creator A5070993902 @default.
• W4226068571 creator A5082411167 @default.
• W4226068571 creator A5087672907 @default.
• W4226068571 creator A5091035596 @default.
• W4226068571 date "2021-11-02" @default.
• W4226068571 modified "2023-09-27" @default.
• W4226068571 title "CTNI-01. A PHASE 1-2 CLINICAL TRIAL OF EO1001 (APL-122), A NOVEL IRREVERSIBLE PAN-ERBB INHIBITOR WITH PROMISING BRAIN PENETRATION" @default.
• W4226068571 doi "https://doi.org/10.1093/neuonc/noab196.226" @default.
• W4226068571 hasPublicationYear "2021" @default.
• W4226068571 type Work @default.
• W4226068571 citedByCount "0" @default.
• W4226068571 crossrefType "journal-article" @default.
• W4226068571 hasAuthorship W4226068571A5004569486 @default.
• W4226068571 hasAuthorship W4226068571A5010965225 @default.
• W4226068571 hasAuthorship W4226068571A5013583484 @default.
• W4226068571 hasAuthorship W4226068571A5014794937 @default.
• W4226068571 hasAuthorship W4226068571A5016462836 @default.
• W4226068571 hasAuthorship W4226068571A5020548821 @default.
• W4226068571 hasAuthorship W4226068571A5036712029 @default.
• W4226068571 hasAuthorship W4226068571A5049181098 @default.
• W4226068571 hasAuthorship W4226068571A5049351775 @default.
• W4226068571 hasAuthorship W4226068571A5050440486 @default.
• W4226068571 hasAuthorship W4226068571A5066896961 @default.
• W4226068571 hasAuthorship W4226068571A5070993902 @default.
• W4226068571 hasAuthorship W4226068571A5082411167 @default.
• W4226068571 hasAuthorship W4226068571A5087672907 @default.
• W4226068571 hasAuthorship W4226068571A5091035596 @default.
• W4226068571 hasBestOaLocation W42260685711 @default.
• W4226068571 hasConcept C112705442 @default.
• W4226068571 hasConcept C121608353 @default.
• W4226068571 hasConcept C126322002 @default.
• W4226068571 hasConcept C143998085 @default.
• W4226068571 hasConcept C2779251935 @default.
• W4226068571 hasConcept C29730261 @default.
• W4226068571 hasConcept C71924100 @default.
• W4226068571 hasConcept C98274493 @default.
• W4226068571 hasConceptScore W4226068571C112705442 @default.
• W4226068571 hasConceptScore W4226068571C121608353 @default.
• W4226068571 hasConceptScore W4226068571C126322002 @default.
• W4226068571 hasConceptScore W4226068571C143998085 @default.
• W4226068571 hasConceptScore W4226068571C2779251935 @default.
• W4226068571 hasConceptScore W4226068571C29730261 @default.
• W4226068571 hasConceptScore W4226068571C71924100 @default.
• W4226068571 hasConceptScore W4226068571C98274493 @default.
• W4226068571 hasIssue "Supplement_6" @default.
• W4226068571 hasLocation W42260685711 @default.
• W4226068571 hasLocation W42260685712 @default.
• W4226068571 hasOpenAccess W4226068571 @default.
• W4226068571 hasPrimaryLocation W42260685711 @default.
• W4226068571 hasRelatedWork W1982282930 @default.
• W4226068571 hasRelatedWork W1995586676 @default.
• W4226068571 hasRelatedWork W2074629895 @default.
• W4226068571 hasRelatedWork W2141289501 @default.
• W4226068571 hasRelatedWork W2323576217 @default.
• W4226068571 hasRelatedWork W2398231413 @default.
• W4226068571 hasRelatedWork W2774225352 @default.
• W4226068571 hasRelatedWork W2991030316 @default.
• W4226068571 hasRelatedWork W3080441546 @default.
• W4226068571 hasRelatedWork W4214585610 @default.
• W4226068571 hasVolume "23" @default.
• W4226068571 isParatext "false" @default.
• W4226068571 isRetracted "false" @default.
• W4226068571 workType "article" @default.