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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorAmeratunga, Malaka
dc.contributor.authorBraña Garcia, Irene
dc.contributor.authorBono, Petri
dc.contributor.authorPostel-Vinay, Sophie
dc.contributor.authorPlummer, Ruth
dc.contributor.authorAspegren, John
dc.date.accessioned2021-10-29T11:56:31Z
dc.date.available2021-10-29T11:56:31Z
dc.date.issued2020-12-08
dc.identifier.citationAmeratunga M, Braña I, Bono P, Postel-Vinay S, Plummer R, Aspegren J, et al. First-in-human Phase 1 open label study of the BET inhibitor ODM-207 in patients with selected solid tumours. Br J Cancer. 2020 Dec 8;123(12):1730–6.
dc.identifier.issn1532-1827
dc.identifier.urihttp://hdl.handle.net/11351/6488
dc.descriptionDrug development; Melanoma
dc.description.abstractBackground Bromodomain and extra-terminal domain (BET) proteins are reported to be epigenetic anti-cancer drug targets. This first-in-human study evaluated the safety, pharmacokinetics and preliminary anti-tumour activity of the BET inhibitor ODM-207 in patients with selected solid tumours. Methods This was an open-label Phase 1 study comprised of a dose escalation part, and evaluation of the effect of food on pharmacokinetics. ODM-207 was administered orally once daily. The dose escalation part was initiated with a dose titration in the initial cohort, followed by a 3 + 3 design. Results Thirty-five patients were treated with ODM-207, of whom 12 (34%) had castrate-resistant prostate cancer. One dose-limiting toxicity of intolerable fatigue was observed. The highest studied dose achieved was 2 mg/kg due to cumulative toxicity observed beyond the dose-limiting toxicity (DLT) treatment window. Common AEs included thrombocytopenia, asthenia, nausea, anorexia, diarrhoea, fatigue, and vomiting. Platelet count decreased proportionally to exposure with rapid recovery upon treatment discontinuation. No partial or complete responses were observed. Conclusions ODM-207 shows increasing exposure in dose escalation and was safe at doses up to 2 mg/kg but had a narrow therapeutic window.
dc.language.isoeng
dc.publisherSpringer Nature
dc.relation.ispartofseriesBritish Journal of Cancer;123(12)
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectCàncer - Quimioteràpia
dc.subjectMedicaments antineoplàstics
dc.subject.meshNeoplasms
dc.subject.mesh/drug therapy
dc.subject.meshAntineoplastic Agents
dc.titleFirst-in-human Phase 1 open label study of the BET inhibitor ODM-207 in patients with selected solid tumours
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1038/s41416-020-01077-z
dc.subject.decsneoplasias
dc.subject.decs/farmacoterapia
dc.subject.decsantineoplásicos
dc.relation.publishversionhttps://doi.org/10.1038/s41416-020-01077-z
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Ameratunga M] The Institute of Cancer Research and Royal Marsden, London, UK. Monash University, Melbourne, Australia. [Braña I] Vall d’Hebron Institut of Oncology (VHIO), Barcelona, Spain. [Bono P] Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland. University of Helsinki, Helsinki, Finland. Terveystalo Finland and University of Helsinki, Helsinki, Finland. [Postel-Vinay S] Drug Development Department, DITEP, Gustave Roussy, Villejuif, France. [Plummer R] Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. [Aspegren J] Orion Corporation Orion Pharma, Espoo, Finland
dc.identifier.pmid32989226
dc.identifier.wos000573406600001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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