Doi, Toshihiko, Onozawa, Yusuke, Yoshino, Takayuki, Yamazaki, Kentaro, Junichiro, Watanabe, Akimov, Mikhail, Robson, Matthew, Boku, Narikazu and Ohtsu, Atsushi (2014) Phase I Dose-Escalation Study of the HSP90 Inhibitor AUY922 in Japanese Patients with Advanced Solid Tumors. Cancer Chemotherapy Pharmacology .

Abstract

Purpose: AUY922 is a potent non-geldanamycin inhibitor of heat-shock protein 90. This study was carried out in Japanese patients to determine the maximum tolerated dose (MTD), and to characterise safety, tolerability and pharmacokinetics of single-agent AUY922.
Methods: Japanese patients with advanced solid tumors whose disease had progressed on at least one line of standard therapy, or for whom no standard therapy existed, were treated with AUY922 (intravenous, once-weekly, 28-day cycle, starting dose 8 mg/m2).
Results: Thirty-one patients were treated. Two DLTs were reported in one patient of the 54 mg/m2 cohort; fatigue and decreased appetite (both Grade 3, resolving to Grade1 within 8 days). No MTD was determined, and the dose recommended for Phase II studies was determined to be 70 mg/m2 once-weekly. Most common drug-related toxicities were diarrhea, night blindness and nausea. Grade 1 and 2 visual toxicities at high AUY922 doses ≥22 mg/m2 were observed. Ten patients (32%) achieved a best overall response of stable disease and one patient (3%) achieved a confirmed partial response.
Conclusion: Overall, AUY922 exhibited acceptable toxicities and demonstrated potential clinical activity in Japanese patients, with similar safety and pharmacokinetic profiles to those reported in a preceding global Phase I study in Western patients (CAUY922A2101).

Item Type:	Article
Keywords:	AUY922; Clinical trial; HSP90; Japanese; Phase I
Date Deposited:	13 Oct 2015 13:13
Last Modified:	13 Oct 2015 13:13
URI:	https://oak.novartis.com/id/eprint/21581