臨床研究等提出・公開システム

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER TRIAL OF TAS-116 IN PATIENTS WITH ADVANCED GASTROINTESTINAL STROMAL TUMOR (GIST)

A phase 3 study of TAS-116 in patients with GIST

86

Baseline characteristics were generally well balanced between treatment groups. The number of male patients was 34/58 (58.6%) in the TAS-116 group and 15/28 (53.6%) in the placebo group. The median age was 62.0 years (range, 32 to 83 years) in the TAS-116 group and 61.5 years (range, 26 to 81 years) in the placebo group. ECOG PS was 0 in 49/58 patients (84.5%) in the TAS-116 group and 24/28 patients (85.7%) in the placebo group.

86 patients were randomized and received >=1 dose of TAS-116 (n = 58) or placebo (n = 28).

The most common (>=30%) treatment-related adverse events (AEs) with TAS-116 were diarrhea (74.1%) and decreased appetite (31.0%); the most common (>=10%) grade >=3 treatment-related AE was diarrhea (13.8%). Treatment-related serious AEs were reported in six (10.3%) patients in the pimitespib group. Treatment-related AEs leading to TAS-116 discontinuation occurred in three (5.2%) patients. No treatment-related deaths occurred during the study

Median PFS by blinded central radiological review (BCRR) was 2.8 months [95% CI 1.6-2.9 months] with TAS-116 versus 1.4 months (0.9-1.8 months) with placebo [HR 0.51 (95% CI 0.30-0.87); one-sided P = 0.006].

In an analysis of OS to adjust for cross-over effect, median OS was 13.8 months (95% CI 9.2 months-Not Reached) with TAS-116 and 7.6 months (5.3-14.9 months) with placebo [HR 0.42 (95% CI 0.21-0.85), one-sided P = 0.007].

TAS-116 significantly improved PFS and cross-over-adjusted OS compared with placebo and had an acceptable safety profile in patients with advanced GIST refractory to standard TKIs.

July. 07, 2022

https://www.annalsofoncology.org/article/S0923-7534(22)01718-5/fulltext

No

Data will not be shared according to the Sponsor policy on data sharing. Taiho policy on data sharing may be found at https://www.taiho.co.jp/en/science/policy/clinical_trial_information_disclosure_policy/index.html.

Taiho Pharmaceutical Co., Ltd.

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toiawaseCD1@taiho.co.jp

Taiho Pharmaceutical Co., Ltd.

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toiawase@taiho.co.jp

completed

Oct. 31, 2018

Interventional

Double-blind, two-arm, randomized phase III study

treatment purpose

3

Key inclusion criteria
- Provided written informed consent
- Histologically confirmed GIST.
- Have had previous treatments of imatinib, sunitinib and regorafenib
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

Key exclusion criteria
- A serious illness or medical condition
- Previous or concurrent cancer that is distinct in primary disease or histology from the cancer that is being evaluated in this study. (Cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (stage Ta, Tis and T1), cancers corresponding to intraepithelial or intramucosal neoplasia and any previous cancer curatively treated more than 5 years before the enrollment can be eligible.)
- Pregnant or lactating female (including the cessation of lactation) or females of child-bearing potential who have a positive pregnancy test proceeded during the Baseline Period.

Both

GIST

investigational material(s)
Generic name etc : TAS-116
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : The starting dose of TAS-116 will be given 160 mg/body orally, 5 days on/2 days off in patients with GIST.

control material(s)
Generic name etc : Placebo
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : Placebo will be administered in orally and 5 days on/2 days off.

efficacy
Efficacy
RECIST(Ver.1.1)

safety
pharmacokinetics
pharmacogenomics
Safety, Pharmacokinetics, Pharmacogenomics
CTCAE(Ver.4.03)

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Sept. 17, 2018