Sistema de Salut de Catalunya
Institut Català de la Salut
[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
Vall d'Hebron Barcelona Hospital Campus
2021-10-29T11:56:31Z
2021-10-29T11:56:31Z
2020-12-08
Desenvolupament de fàrmacs; Melanoma
Desarrollo de fármacos; Melanoma
Drug development; Melanoma
Background 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.
The study was sponsored by Orion Corporation, Orion Pharma, Espoo, Finland, the developer of ODM-207.
Article
Published version
English
Càncer - Quimioteràpia; Medicaments antineoplàstics; DISEASES::Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents; ENFERMEDADES::neoplasias; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
Springer Nature
British Journal of Cancer;123(12)
https://doi.org/10.1038/s41416-020-01077-z
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
