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dc.contributor.authorRobbrecht, DGJ
dc.contributor.authorLopez, J
dc.contributor.authorCalvo, E
dc.contributor.authorHe, X
dc.contributor.authorHiroshi, H
dc.contributor.authorSoni, N
dc.contributor.authorCook, N
dc.contributor.authorDowlati, A
dc.contributor.authorFasolo, A
dc.contributor.authorMoreno, V
dc.contributor.authorEskens, FALM
dc.contributor.authorde Bono, JS
dc.date.accessioned2021-11-02T10:33:05Z
dc.date.available2021-11-02T10:33:05Z
dc.identifier.citationBritish journal of cancer, 2021, 124 (2), pp. 391 - 398
dc.identifier.issn0007-0920
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4866
dc.identifier.eissn1532-1827
dc.identifier.doi10.1038/s41416-020-01100-3
dc.description.abstractBackground This is a first-in-human study with TAS-119, an Aurora A kinase (AurA) inhibitor. Methods Patients with advanced, refractory, solid tumours were enrolled into 5 dose escalation cohorts (70-300 mg BID, 4 days on/3 days off, 3 out of 4 weeks or 4 out of 4 weeks). The expansion part consisted of patients with small-cell lung cancer, HER2-negative breast cancer, MYC-amplified/β-catenin-mutated (MT) tumours or other (basket cohort). Results In the escalation part (n = 34 patients), dose-limiting toxicities were one grade 3 nausea, two grade 2 and one grade 3 ocular toxicity and a combination of fatigue, ocular toxicity and nausea in one patient (all grade 2) at dose levels of 150, 200, 250 and 300 mg, respectively. Most frequent treatment-related adverse events were fatigue (32%), diarrhoea (24%) and ocular toxicity (24%). Toxicity grade ≥3 in ≥10% of patients were diarrhoea (15%) and increased lipase (12%). The maximum tolerated dose was 250 mg BID. Due to one additional grade 1 ocular toxicity, the RP2D was set at 200 mg BID (4 days on/3 days off, 3 out of 4 weeks), which was further explored in the expansion part (n = 40 patients). Target inhibition in paired skin biopsies was shown. Conclusions TAS-119 has a favourable and remarkably distinct safety profile from other AurA inhibitors. Clinical trial registration NCT02448589.
dc.formatPrint-Electronic
dc.format.extent391 - 398
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectAntineoplastic Agents
dc.subjectProtein Kinase Inhibitors
dc.subjectMaximum Tolerated Dose
dc.subjectDose-Response Relationship, Drug
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectAurora Kinase A
dc.titleA first-in-human phase 1 and pharmacological study of TAS-119, a novel selective Aurora A kinase inhibitor in patients with advanced solid tumours.
dc.typeJournal Article
dcterms.dateAccepted2020-09-10
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41416-020-01100-3
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBritish journal of cancer
pubs.issue2
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Early Phase Drug Development
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.publication-statusPublished
pubs.volume124
pubs.embargo.termsNot known
icr.researchteamEarly Phase Drug Development
icr.researchteamProstate Cancer Targeted Therapy Group
dc.contributor.icrauthorLopez, Juanitaen_US
dc.contributor.icrauthorDe Bono, Johannen_US


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