臨床研究等提出・公開システム

PHASE 1/2 STUDY OF TAS-120 IN PATIENTS WITH ADVANCED SOLID TUMORS HARBORING FGF/FGFR ABERRATIONS

Phase I/II study of TAS-120

103

-The median age of the patients was 58 years, with a range of 22 to 79. -Female: 58 patients (56%), Male: 45 patients (44%) -ECOG PS0: 48 patients (47%), PS1: 55 patients (53%) -Japan: 14 patients (14%), North America: 47 patients (46%), Europe: 28 patients (27%), Asia Pacific, excluding Japan: 14 patients (14%)

At the data-cutoff date for the primary analysis on October 1, 2020, the median follow-up was 17.1 months (range, 10.1 to 29.6). The median duration of treatment was 9.1 months. Out of the 103 enrolled patients, 72 (70%) discontinued treatment. The main reasons for discontinuation were radiologic or clinical disease progression (62%) and less commonly adverse events (5%). Thirteen patients (13%) received futibatinib after radiologic disease progression due to continued clinical benefit.

All patients in the study experienced at least one adverse event of any cause. The most frequent treatment-related adverse events of any grade (in >= 25% of patients) were: -Hyperphosphatemia: 85% -Alopecia: 33% -Dry mouth: 30% -Diarrhea: 28% -Dry skin: 27% -Fatigue: 25% The most common grade 3 treatment-related adverse event was hyperphosphatemia (in 30% of patients). Other grade 3 treatment-related adverse events included increased aspartate aminotransferase level, stomatitis, and fatigue. Serious treatment-related adverse events were reported in 10 patients (10%). Hyperphosphatemia had an early onset, with a median of 5 days. It was manageable with phosphate-lowering therapy in 78% of patients. Other adverse events commonly reported in patients who received FGFR inhibitors included nail disorders and retinal disorders, which were generally mild. Treatment-related adverse events led to dose interruptions in 52 patients (50%) and dose reductions in 56 patients (54%). Two patients (2%) permanently discontinued futibatinib due to treatment-related adverse events.

Objective response rate: 42% (95% confidence interval, 32 to 52, 43/103 patients)

Responses to futibatinib were consistent across patient subgroups, including those with heavily pretreated disease, older adults, and patients with co-occurring TP53 mutations. With the median follow-up of 17.1 months: -The median duration of response was 9.7 months. -The median progression-free survival was 9.0 months. -The median overall survival was 21.7 months. -Quality of life was maintained throughout the treatment.

In previously treated patients with FGFR2 fusion or rearrangement positive intra-hepatic cholangiocarcinoma, the use of futibatinib, a covalent FGFR inhibitor, led to clinically significant benefit.

Jan. 19, 2023

https://www.nejm.org/doi/full/10.1056/NEJMoa2206834

No

Taiho Pharmaceutical Co., Ltd.

1-27 Kandanishiki-cho, Chiyoda-ku, Tokyo

toiawaseCD1@taiho.co.jp

Taiho Pharmaceutical Co., Ltd.

1-27 Kandanishiki-cho, Chiyoda-ku, Tokyo

+81-3-3293-2113

toiawase@taiho.co.jp

completed

July. 24, 2018

Interventional

This is an open-label, nonrandomized, dose-escalation and dose-expansion, Phase 1/2 study.

treatment purpose

1-2

1. Provide written informed consent.
2. Is >= 20 years.
3. Has histologically or cytologically confirmed, locally advanced, metastatic cancer.
4. Patient has measurable disease.
5. ECOG performance status 0 or 1.
6. Able to take medications orally.
7. Adequate organ function.
8. Have a negative pregnancy test.
9. Willing and able to comply with scheduled visits and study procedures.

1. History and/or current evidence of non-tumor related alteration of calcium-phosphorus homeostasis.
2. History and/or current evidence of clinically significant ectopic mineralization/calcification.
3. History and/or current evidence of clinically significant retinal disorder confirmed by retinal examination.
4. A serious illness or medical condition(s)

Both

solid tumors

investigational material(s)
Generic name etc : TAS-120 : futibatinib
INN of investigational material : TAS-120 : futibatinib
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : TAS-120 will be administered orally once daily.

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

safety
efficacy
Safety, Efficacy

safety
efficacy
Safety, Efficacy
CTCAE(version 4.03), RECIST(version 1.1)

June. 20, 2018