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A Multicenter Phase II Basket-type Clinical Trial to Evaluate Efficacy and Safety of TAS-120 in Patients with Advanced Solid Malignancies with FGFR Alterations in Circulating Tumor DNA

TiFFANY Study

26

The median(min-max) age of 26 patients in Full Analysis Set (FAS) was 59.5 (37-78) years. Sex was male in 14 patients (53.8%) and female in 12 patients (46.2%). Performance status was "0" in 12 patients (46.2%) and "1" in 14 patients (53.8%). Cancer types were esophageal cancer in 2 patients (7.7%), gastric cancer in 4 patients(15.4%), colorectal cancer in 3 patients(11.5%), cholangiocarcinoma in 3 patients(11.5%), lung cancer in 2 patients(7.7%), thymoma in a patient(3.8%), urothelial carcinoma in 4 patients(15.4%),urachal cancer in a patient(3.8%),breast cancer in 2 patients(7.7%), endometrial and ovarian cancer in 4 patients(15.4%). Types of FGFR alterations were fusion in 4 patients(15.4%),amplification in 13 patients(50.0%),and mutation in 9 patients(34.6%)

Signed informed consent: 26 patients Registered: 26 patients Completed study treatment: none Discontinued from the study: 26 patients

Of 26 patients in Safety Population (SP), adverse events that occurred in more than 20% of the patients were hyperphosphatemia (100.0%: 26 patients), diarrhea (42.3%: 11 patients), anorexia (38.5%: 10 patients), nausea (34.6%: 9 patients), dysgeusia (34.6%: 9 patients), increased alanine aminotransferase (30.8%: 8 patients), increased aspartate aminotransferase (30.8%: 8 patients), and stomatitis (26.9%: 7 patients). Grade 3 adverse events were hyperphosphatemia (30.8%: 8 patients), increased alanine aminotransferase (7.7%: 2 patients), anemia, stomatitis, increased aspartate aminotransferase, and neutropenia (3.8%: a patient, respectively), with no Grade 4 or higher adverse events observed. Grade 5 adverse events that occurred were multiple organ failure and acute lymphocytic leukemia unrelated to treatment (3.8%: a patient, respectively), and no treatment-related deaths were observed. Serious adverse events were reported in 6 of 26 patients (23.1%), including anorexia, tumor pain, acute lymphocytic leukemia, transient ischemic attack, ileus, and multiple organ failure, all of which were unrelated to treatment.

Five patients were confirmed responders by investigator-assessment (best overall response was CR or PR), and confirmed objective response rate (confirmed ORR) was 19.2% (95% confidence interval: 6.6% - 39.4%). The null hypothesis was rejected because the lower limit of the 95% confidence interval exceeded the threshold Confirmed ORR of 5% (p-value = 0.0085 < corresponding to a one-sided significance level of 2.5%). Confirmed objective responses were observed in urachal cancer with FGFR amplification, urothelial carcinoma with FGFR mutation, gastric cancer with FGFR amplification, and cholangiocarcinoma with FGFR fusion.

Median progression free survival in 26 patients of FAS was 2.6 months (95% confidence interval, the same hereinafter: 1.4 months - 4.2 months). Median duration of response for the 5 responders was 6.9 months (2.7 months - not estimable). Median time to treatment failure was 2.3 months (1.4 months - 4.2 months). Eighteen patients had controlled disease (best overall response was CR, PR, or SD lasting at least 5 weeks), and disease control rate was 69.2% (48.2% - 85.7%). Median overall survival was 8.9 months (5.5 months - 10.6 months).

TAS-120 demonstrated promising efficacy in refractory advanced solid malignancies with FGFR alterations in circulating tumor DNA with an acceptable toxicity profile.

No

National Cancer Center Hospital East

6-5-1,Kashiwanoha,Kashiwa,Chiba,277-8577,Japan

TiFFANY_core@east.ncc.go.jp

National Cancer Center Hospital East

6-5-1,Kashiwanoha,Kashiwa,Chiba,277-8577,Japan

+81-4-7134-6854

TiFFANY_core@east.ncc.go.jp

completed

June. 17, 2019

Interventional

open-label, single arm, multicenter phase II basket-type study

treatment purpose

2

1.Informed consent for participation in the study is obtained at the discretion of the patient.
2.The patient is 20 years of age or older on the date of informed consent.
3.Histologically or cytologically confirmed an unresectable advanced or recurrent solid malignancy without standard treatment remains.
4.The following genomic alteration is detected by analysis of blood sample using Guardant360:
I.FGFR fusion
II.FGFR amplification
III.FGFR mutation
5.The disease is measurable based on the Response Evaluation Criteria in Solid Tumours (RECIST) guidelines version 1.1

1.History and/or current evidence of endocrine alteration of calcium-phosphate homeostasis.
2.History and/or current evidence of ectopic mineralization/calcification including but not limited to the soft tissue, kidneys, intestine, myocard and lung with the exception of calcified lymph nodes and asymptomatic coronary calcification.
3.Current evidence of corneal disorder/keratopathy including but not limited to bullous/ band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis etc., confirmed by ophthalmologic examination.
4.History or current evidence of cardiac arrhythmia and/or conduction abnormality.

Both

solid malignancies

investigational material(s)
Generic name etc : TAS-120
INN of investigational material : TAS-120
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : TAS-120 20 mg once daily, orally, in a 21 day-cycle.

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

efficacy
objective response rate(ORR) assessed by investigators

safety
efficacy
Progression-free survival(PFS),Duration of response(DoR), Time to treatment failure(TTF),Disease control rate(DCR),Overall survival(OS),ORR by central assessment(ORR),AE

+81-4-7133-1111

May. 22, 2019