Publications Repository

Publications Repository

View item 
  •   Home
  • ICR Divisions
  • Clinical Studies
  • View item
  • Home
  • ICR Divisions
  • Clinical Studies
  • View item
JavaScript is disabled for your browser. Some features of this site may not work without it.

First-in-Human Phase I Study of an Oral HSP90 Inhibitor, TAS-116, in Patients with Advanced Solid Tumors.

Thumbnail
View/Open
Accepted version (1.421Mb)
Date
2019-03
ICR Author
Turner, Lydia
Banerji, Udai
Author
Shimomura, A
Yamamoto, N
Kondo, S
Fujiwara, Y
Suzuki, S
Yanagitani, N
Horiike, A
Kitazono, S
Ohyanagi, F
Doi, T
Kuboki, Y
Kawazoe, A
Shitara, K
Ohno, I
Banerji, U
Sundar, R
Ohkubo, S
Calleja, EM
Nishio, M
Show allShow less
Type
Journal Article
Metadata
Show full item record
Abstract
HSP90 is involved in stability and function of cancer-related proteins. This study was conducted to define the MTD, safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor efficacy of TAS-116, a novel class, orally available, highly selective inhibitor of HSP90. Patients with advanced solid tumors received TAS-116 orally once daily (QD, step 1) or every other day (QOD, step 2) in 21-day cycles. Each step comprised a dose escalation phase to determine MTD and an expansion phase at the MTD. In the dose escalation phase, an accelerated dose-titration design and a "3+3" design were used. Sixty-one patients were enrolled in Japan and the United Kingdom. MTD was determined to be 107.5 mg/m 2 /day for QD, and 210.7 mg/m 2 /day for QOD. In the expansion phase of step 1, TAS-116 was administered 5 days on/2 days off per week (QD × 5). The most common treatment-related adverse events included gastrointestinal disorders, creatinine increases, AST increases, ALT increases, and eye disorders. Eye disorders have been reported with HSP90 inhibitors; however, those observed with TAS-116 in the expansion phases were limited to grade 1. The systemic exposure of TAS-116 increased dose-proportionally with QD and QOD regimens. Two patients with non-small cell lung cancer and one patient with gastrointestinal stromal tumor (GIST) achieved a confirmed partial response. TAS-116 had an acceptable safety profile with some antitumor activity, supporting further development of this HSP90 inhibitor.This is a result from a first-in-human study, in which the HSP90 inhibitor TAS-116 demonstrated preliminary antitumor efficacy in patients with advanced solid tumors, including those with heavily pretreated GIST.
URI
https://repository.icr.ac.uk/handle/internal/3151
DOI
https://doi.org/10.1158/1535-7163.mct-18-0831
Collections
  • Cancer Therapeutics
  • Clinical Studies
Subject
Cell Line, Tumor
Humans
Carcinoma, Non-Small-Cell Lung
Gastrointestinal Stromal Tumors
Benzamides
Pyrazoles
Protein Kinase Inhibitors
Administration, Oral
Maximum Tolerated Dose
Adult
Aged
Middle Aged
Japan
Female
Male
HSP90 Heat-Shock Proteins
United Kingdom
Research team
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)
Language
eng
Date accepted
2019-01-11
License start date
2019-03
Citation
Molecular cancer therapeutics, 2019, 18 (3), pp. 531 - 540

Browse

All of ICR repositoryICR DivisionsBy issue dateAuthorsTitlesPublication TypesThis collectionBy issue dateAuthorsTitlesPublication Types
  • Login
  • Registered office: The Institute of Cancer Research, 123 Old Brompton Road, London, SW7 3RP
    A Charity, Not for Profit. Company Limited by Guarantee.
    Registered in England No. 534147. VAT Registration No. GB 849 0581 02.