Abstract:
:Background AZD4547 is a potent, oral, highly selective fibroblast growth factor receptor (FGFR) inhibitor in clinical development for treating tumours with a range of FGFR aberrations, including FGFR mutations, amplifications and fusions. Methods This open-label, Phase I, multicentre study (NCT01213160) evaluated the safety, pharmacokinetics, and preliminary antitumour efficacy (RECIST v1.1) of AZD4547 monotherapy in Japanese patients with advanced solid tumours. Part A was a dose-escalation part; Part B was a dose-expansion part in patients with FGFR-amplified tumours, confirmed by fluorescence in situ hybridization. Results Thirty patients enrolled in Part A (dose range: 40 mg twice daily [bid] to 120 mg bid; 160 mg once daily [qd]), four in Part B (80 mg bid). No dose-limiting toxicities were observed and maximum tolerated dose was not determined. Most common adverse events (AEs; any grade) were: dysgeusia (50% of patients); stomatitis (41%); diarrhoea (38%); hyperphosphataemia (38%); dry mouth (35%). Common grade ≥3 AEs were nausea (12% of patients) and neutropenia (9%). No complete or partial responses were observed: 21/30 patients had stable disease ≥4 weeks in Part A, and 1/4 patients had stable disease ≥10 weeks in Part B. Following single and multiple dosing, absorption rate appeared moderate; peak plasma concentrations generally occurred 3-4 h post-dose, then declined biphasically with terminal half-life ~30 h. Steady state was reached by day 8. Compared with single dosing, plasma concentrations were, on average, 2.4- and 3.3- to 5.4-fold higher after qd and bid dosing, respectively. Conclusions AZD4547 was well tolerated in Japanese patients, with best response of stable disease ≥4 weeks.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Saka H,Kitagawa C,Kogure Y,Takahashi Y,Fujikawa K,Sagawa T,Iwasa S,Takahashi N,Fukao T,Tchinou C,Landers D,Yamada Ydoi
10.1007/s10637-016-0416-xsubject
Has Abstractpub_date
2017-08-01 00:00:00pages
451-462issue
4eissn
0167-6997issn
1573-0646pii
10.1007/s10637-016-0416-xjournal_volume
35pub_type
杂志文章,多中心研究abstract::We previously found that the novel histone deacetylase inhibitor (HDACI) butyroyloxymethyl diethylphosphate (AN-7) had greater selectivity against cutaneous T-cell lymphoma (CTCL) than SAHA. AN-7 synergizes with doxorubicin (Dox), an anthracycline antibiotic that induces DNA breaks. This study aimed to elucidate the m...
journal_title:Investigational new drugs
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journal_title:Investigational new drugs
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abstract:BACKGROUND:Hepatocellular carcinoma (HCC) cells are auxotrophic for arginine, depletion of which leads to tumour regression. The current study evaluated safety, pharmacokinetics (PK)/ pharmacodynamics (PD) parameters, and potential anti-tumor activity of pegylated recombinant human arginase 1 (peg-rhArg1) in advanced H...
journal_title:Investigational new drugs
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章,评审
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pub_type: 杂志文章,评审
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journal_title:Investigational new drugs
pub_type: 杂志文章,评审
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更新日期:2013-04-01 00:00:00
abstract::Background To determine the feasibility and efficacy of olanzapine, which is approved by the Pharmaceuticals and Medical Devices Agency as multi acting receptor targeted antipsychotic agent of the thienobenzodiazepine class, for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients undergoing conti...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
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更新日期:1989-07-01 00:00:00