dc.contributor.author | Robbrecht, DGJ | |
dc.contributor.author | Lopez, J | |
dc.contributor.author | Calvo, E | |
dc.contributor.author | He, X | |
dc.contributor.author | Hiroshi, H | |
dc.contributor.author | Soni, N | |
dc.contributor.author | Cook, N | |
dc.contributor.author | Dowlati, A | |
dc.contributor.author | Fasolo, A | |
dc.contributor.author | Moreno, V | |
dc.contributor.author | Eskens, FALM | |
dc.contributor.author | de Bono, JS | |
dc.date.accessioned | 2021-11-02T10:33:05Z | |
dc.date.available | 2021-11-02T10:33:05Z | |
dc.date.issued | 2021-01-19 | |
dc.identifier.citation | British journal of cancer, 2021, 124 (2), pp. 391 - 398 | |
dc.identifier.issn | 0007-0920 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4866 | |
dc.identifier.eissn | 1532-1827 | |
dc.identifier.doi | 10.1038/s41416-020-01100-3 | |
dc.description.abstract | BACKGROUND: 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.format | Print-Electronic | |
dc.format.extent | 391 - 398 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | SPRINGERNATURE | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Neoplasms | |
dc.subject | Antineoplastic Agents | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Maximum Tolerated Dose | |
dc.subject | Dose-Response Relationship, Drug | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Aurora Kinase A | |
dc.title | A 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.type | Journal Article | |
dcterms.dateAccepted | 2020-09-10 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41416-020-01100-3 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | British journal of cancer | |
pubs.issue | 2 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 124 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Early Phase Drug Development | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | |
dc.contributor.icrauthor | De Bono, Johann | |