First-in-human phase I dose escalation study of the Bromodomain and Extra-Terminal motif (BET) inhibitor BAY 1238097 in subjects with advanced malignancies
Background: BET proteins play an essential role in regulation of transcription of genes involved in cell proliferation and survival, including oncogenes such as MYC. BAY 1238097, a potent highly selective inhibitor of BET proteins suppresses MYC expression and inhibits tumor growth in preclinical mo...
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Veröffentlicht in: | European journal of cancer (1990) 2016-12, Vol.69, p.S7-S8 |
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Sprache: | eng |
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Zusammenfassung: | Background: BET proteins play an essential role in regulation of transcription of genes involved in cell proliferation and survival, including oncogenes such as MYC. BAY 1238097, a potent highly selective inhibitor of BET proteins suppresses MYC expression and inhibits tumor growth in preclinical models. We report here the results of the first-in-human dose-escalation phase 1 trial of BAY 1238097 in patients with advanced malignancies. Material and Methods: Patients with advanced solid tumors or non-Hodgkin lymphoma were eligible for the dose-escalation phase. BAY 1238097 was administered orally twice weekly in a 21-day cycle at a starting dose of 5 mg (10 mg per week; liquid formulation); dose was then escalated following an adaptive dose escalation design and switching to a tablet formulation at the 40 mg (80 mg per week) dose level; planned dosages were 10, 40, 80, 160, 320, 480 and 640 mg per week. Adverse events (AEs) were assessed using CTCAE v4.03. Primary objectives were to determine the safety, pharmacokinetics (PK), maximum tolerated dose (MTD), and recommended phase II dose (RP2D); additional objectives included exploration of target-mediated biomarker modulation. Results: A total of 8 patients (5 female, 3 male), average age 64 years (range: 44-76 years) received at least one dose of study drug. Six patients (3 in the 10mg and 3 in the 40 mg cohorts) were treated without dose-limiting toxicity (DLT), although several (n = 3 of 5) patients experienced recurrent headaches ( |
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ISSN: | 0959-8049 1879-0852 |
DOI: | 10.1016/S0959-8049(16)32620-X |