TY - JOUR
T1 - First-in-human Phase 1 open label study of the BET inhibitor ODM-207 in patients with selected solid tumours
AU - Ameratunga, Malaka
AU - Braña, Irene
AU - Bono, Petri
AU - Postel-Vinay, Sophie
AU - Plummer, Ruth
AU - Aspegren, John
AU - Korjamo, Timo
AU - Snapir, Amir
AU - de Bono, Johann S.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/8
Y1 - 2020/12/8
N2 - 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. Clinical trial registration: The clinical trial registration number is NCT03035591.
AB - 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. Clinical trial registration: The clinical trial registration number is NCT03035591.
UR - http://www.scopus.com/inward/record.url?scp=85091606488&partnerID=8YFLogxK
U2 - 10.1038/s41416-020-01077-z
DO - 10.1038/s41416-020-01077-z
M3 - Article
C2 - 32989226
AN - SCOPUS:85091606488
SN - 0007-0920
VL - 123
SP - 1730
EP - 1736
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 12
ER -