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A Study of TAS-120 in Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT02052778
Recruitment Status : Completed
First Posted : February 3, 2014
Results First Posted : March 20, 2024
Last Update Posted : March 20, 2024
Sponsor:
Information provided by (Responsible Party):
Taiho Oncology, Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Cholangiocarcinoma
Urothelial Cancer
Advanced and Metastatic Cancer Patients With Tumors Harboring FGF/FGFR Tumors
Primary CNS Tumors
Breast Cancer
Gastric Cancer
Intervention Drug: Futibatinib
Enrollment 407
Recruitment Details Study had Phase 1 and 2. Phase 1 included Dose escalation: 86 participants were enrolled & treated and Dose Expansion: 284 participants were screened, of which 201 were enrolled; 197 were treated & 4 were not treated. Phase 2: 120 participants signed informed consent, of which 17 were screen failures & thus 103 were treated. In Participant Flow, Baseline Characteristics & Adverse events, combined arm presentation of QOD & QD dosing was made for Phase 1 Dose Escalation as pre-planned in protocol.
Pre-assignment Details All Phase 1 Dose Expansion (DE) sub-cohort 1 and 2 participants: efficacy data were presented only per cut-off date (COD) 30-Jun-2019 because they had disease progression & discontinued & thus not available for COD 29-May-2021 analysis. For Phase 1 DE, primary analysis (progression free survival and overall survival) data were presented per COD 30-Jun-2019 as pre planned in protocol. Phase 1 and 2 participants who showed clinical benefit: efficacy data were presented per COD 29-May-2021.
Arm/Group Title Phase 1: Dose Escalation: QOD Dosing: 8 mg Phase 1: Dose Escalation: QOD Dosing: 16 mg Phase 1: Dose Escalation: QOD Dosing: 24 mg Phase 1: Dose Escalation: QOD Dosing: 36 mg Phase 1: Dose Escalation: QOD Dosing: 56 mg Phase 1: Dose Escalation: QOD Dosing: 80 mg Phase 1: Dose Escalation: QOD Dosing: 120 mg Phase 1: Dose Escalation: QOD Dosing: 160 mg Phase 1: Dose Escalation: QOD Dosing: 200 mg Phase 1: Dose Escalation: QD Dosing: 4 mg Phase 1: Dose Escalation: QD Dosing: 8 mg Phase 1: Dose Escalation: QD Dosing: 16 mg Phase 1: Dose Escalation: QD Dosing: 20 mg Phase 1: Dose Escalation: QD Dosing: 24 mg Phase 1: Dose Expansion Cohort 1 Phase 1: Dose Expansion: Cohort 2 Phase 1: Dose Expansion: Cohort 3 Phase 1: Dose Expansion: Cohort 4 Phase 1:Dose Expansion: Cohort 5 Phase 1: Dose Expansion: Cohort 6 Phase 1: Dose Expansion: Sub-cohort 1 Phase 1: Dose Expansion: Sub-cohort 2 Phase 2
Hide Arm/Group Description Participants with or without fibroblast growth factor [FGF]/fibroblast growth factor receptor [FGFR] gene abnormalities received orally TAS-120 8 milligrams (mg) orally every other day (QOD; Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 16 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 24 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 36 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with FGF/FGFR gene abnormalities received orally TAS-120 56 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with FGF/FGFR gene abnormalities received orally TAS-120 80 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with FGF/FGFR gene abnormalities received orally TAS-120 120 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with FGF/FGFR gene abnormalities received orally TAS-120 160 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with FGF/FGFR gene abnormalities received orally TAS-120 200 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received a dose between 4 mg orally once daily (QD) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received a dose between 8 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received a dose between 16 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received a dose between 20 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received a dose between 24 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with intra-hepatic or extrahepatic cholangiocarcinoma (iCCA or eCCA) harboring FGFR2 gene fusions or rearrangements and who were treated or not treated with prior FGFR inhibitors received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with primary central nervous system (CNS) tumors harboring FGFR gene fusions or FGFR1 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with advanced urothelial carcinoma harboring FGFR3 gene fusions or FGFR3 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with breast or gastric cancer with harboring FGFR2 amplification received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with tumor types harboring FGFR gene fusions or activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants who were not included in Cohorts 1 to 5 received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with iCCA who were enrolled prior to the confirmation of the recommended Phase 2 dose (RP2D) received TAS-120 16 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with other tumor types who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Period Title: Dose Escalation(Approximately 60 Months)
Started [1] 6 3 3 3 3 5 4 8 7 4 5 14 7 14 0 0 0 0 0 0 0 0 0
Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Not Completed 6 3 3 3 3 5 4 8 7 4 5 14 7 14 0 0 0 0 0 0 0 0 0
Reason Not Completed
Radiographic progression             4             2             2             1             2             3             0             6             5             4             5             11             4             7             0             0             0             0             0             0             0             0             0
Clinical disease progression             2             1             1             2             1             1             3             2             1             0             0             2             2             3             0             0             0             0             0             0             0             0             0
Adverse Event             0             0             0             0             0             0             0             0             0             0             0             0             0             1             0             0             0             0             0             0             0             0             0
Death             0             0             0             0             0             0             1             0             0             0             0             1             0             0             0             0             0             0             0             0             0             0             0
Withdrawal by participant             0             0             0             0             0             0             0             0             1             0             0             0             0             3             0             0             0             0             0             0             0             0             0
Investigator decision             0             0             0             0             0             1             0             0             0             0             0             0             1             0             0             0             0             0             0             0             0             0             0
[1]
Participants who were enrolled and treated.
Period Title: Dose Expansion (Approximately 59 Months)
Started [1] 0 0 0 0 0 0 0 0 0 0 0 0 0 0 58 35 16 13 25 27 19 8 0
Treated 0 0 0 0 0 0 0 0 0 0 0 0 0 0 57 34 15 13 24 27 19 8 0
Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 58 35 16 13 25 27 19 8 0
Reason Not Completed
Radiographic progression             0             0             0             0             0             0             0             0             0             0             0             0             0             0             38             23             12             11             17             21             14             6             0
Clinical Disease Progression             0             0             0             0             0             0             0             0             0             0             0             0             0             0             6             3             0             2             3             4             5             1             0
Adverse Event             0             0             0             0             0             0             0             0             0             0             0             0             0             0             5             1             3             0             3             1             0             0             0
Withdrawal by Subject             0             0             0             0             0             0             0             0             0             0             0             0             0             0             2             3             0             0             0             0             0             0             0
Investigator decision             0             0             0             0             0             0             0             0             0             0             0             0             0             0             5             3             0             0             0             1             0             0             0
Other             0             0             0             0             0             0             0             0             0             0             0             0             0             0             1             1             0             0             1             0             0             1             0
Untreated             0             0             0             0             0             0             0             0             0             0             0             0             0             0             1             1             1             0             1             0             0             0             0
[1]
Participants who were enrolled.
Period Title: Phase 2 (Approximately 63 Months)
Started [1] 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 120
Treated 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 103
Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 120
Reason Not Completed
Adverse Event             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             7
Radiologic Progression             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             78
Clinical Disease Progression             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             6
Withdrawal by participant             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             2
Investigator Decision             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             3
Other             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             7
Untreated             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             17
[1]
Participants who were enrolled.
Arm/Group Title Phase 1: Dose Escalation: QOD Dosing: 8 mg Phase 1: Dose Escalation: QOD Dosing: 16 mg Phase 1: Dose Escalation: QOD Dosing: 24 mg Phase 1: Dose Escalation: QOD Dosing: 36 mg Phase 1: Dose Escalation: QOD Dosing: 56 mg Phase 1: Dose Escalation: QOD Dosing: 80 mg Phase 1: Dose Escalation: QOD Dosing: 120 mg Phase 1: Dose Escalation: QOD Dosing: 160 mg Phase 1: Dose Escalation: QOD Dosing: 200 mg Phase 1: Dose Escalation: QD Dosing: 4 mg Phase 1: Dose Escalation: QD Dosing: 8 mg Phase 1: Dose Escalation: QD Dosing: 16 mg Phase 1: Dose Escalation: QD Dosing: 20 mg Phase 1: Dose Escalation: QD Dosing: 24 mg Phase 1: Dose Expansion Cohort 1 Phase 1: Dose Expansion: Cohort 2 Phase 1: Dose Expansion: Cohort 3 Phase 1: Dose Expansion: Cohort 4 Phase 1: Dose Expansion: Cohort 5 Phase 1: Dose Expansion: Cohort 6 Phase 1: Dose Expansion: Sub-cohort 1 Phase 1: Dose Expansion: Sub-cohort 2 Phase 2 Total
Hide Arm/Group Description Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 8 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 16 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 24 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 36 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with FGF/FGFR gene abnormalities received orally TAS-120 56 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with FGF/FGFR gene abnormalities received orally TAS-120 80 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with FGF/FGFR gene abnormalities received orally TAS-120 120 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with FGF/FGFR gene abnormalities received orally TAS-120 160 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with FGF/FGFR gene abnormalities received orally TAS-120 200 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received a dose between 4 mg orally once daily (QD) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received a dose between 8 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received a dose between 16 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received a dose between 20 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received a dose between 24 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with intra-hepatic or extrahepatic cholangiocarcinoma (iCCA or eCCA) harboring FGFR2 gene fusions or rearrangements and who were treated or not treated with prior FGFR inhibitors received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with primary central nervous system (CNS) tumors harboring FGFR gene fusions or FGFR1 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with advanced urothelial carcinoma harboring FGFR3 gene fusions or FGFR3 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with breast or gastric cancer with harboring FGFR2 amplification received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with tumor types harboring FGFR gene fusions or activating mutations received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants who were not included in Cohorts 1 to 5 received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with iCCA who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with other tumor types who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Total of all reporting groups
Overall Number of Baseline Participants 6 3 3 3 3 5 4 8 7 4 5 14 7 14 57 34 15 13 24 27 19 8 103 386
Hide Baseline Analysis Population Description
Analysis was performed on all treated population.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 3 participants 3 participants 3 participants 3 participants 5 participants 4 participants 8 participants 7 participants 4 participants 5 participants 14 participants 7 participants 14 participants 57 participants 34 participants 15 participants 13 participants 24 participants 27 participants 19 participants 8 participants 103 participants 386 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
4
  66.7%
2
  66.7%
2
  66.7%
2
  66.7%
2
  66.7%
3
  60.0%
1
  25.0%
6
  75.0%
5
  71.4%
3
  75.0%
3
  60.0%
12
  85.7%
4
  57.1%
11
  78.6%
45
  78.9%
27
  79.4%
5
  33.3%
10
  76.9%
21
  87.5%
18
  66.7%
18
  94.7%
6
  75.0%
80
  77.7%
290
  75.1%
>=65 years
2
  33.3%
1
  33.3%
1
  33.3%
1
  33.3%
1
  33.3%
2
  40.0%
3
  75.0%
2
  25.0%
2
  28.6%
1
  25.0%
2
  40.0%
2
  14.3%
3
  42.9%
3
  21.4%
12
  21.1%
7
  20.6%
10
  66.7%
3
  23.1%
3
  12.5%
9
  33.3%
1
   5.3%
2
  25.0%
23
  22.3%
96
  24.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 3 participants 3 participants 3 participants 3 participants 5 participants 4 participants 8 participants 7 participants 4 participants 5 participants 14 participants 7 participants 14 participants 57 participants 34 participants 15 participants 13 participants 24 participants 27 participants 19 participants 8 participants 103 participants 386 participants
Female
4
  66.7%
1
  33.3%
2
  66.7%
2
  66.7%
0
   0.0%
4
  80.0%
1
  25.0%
4
  50.0%
5
  71.4%
2
  50.0%
0
   0.0%
8
  57.1%
6
  85.7%
13
  92.9%
40
  70.2%
12
  35.3%
4
  26.7%
9
  69.2%
14
  58.3%
16
  59.3%
14
  73.7%
7
  87.5%
58
  56.3%
226
  58.5%
Male
2
  33.3%
2
  66.7%
1
  33.3%
1
  33.3%
3
 100.0%
1
  20.0%
3
  75.0%
4
  50.0%
2
  28.6%
2
  50.0%
5
 100.0%
6
  42.9%
1
  14.3%
1
   7.1%
17
  29.8%
22
  64.7%
11
  73.3%
4
  30.8%
10
  41.7%
11
  40.7%
5
  26.3%
1
  12.5%
45
  43.7%
160
  41.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 3 participants 3 participants 3 participants 3 participants 5 participants 4 participants 8 participants 7 participants 4 participants 5 participants 14 participants 7 participants 14 participants 57 participants 34 participants 15 participants 13 participants 24 participants 27 participants 19 participants 8 participants 103 participants 386 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.1%
2
   3.5%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.7%
1
   5.3%
2
  25.0%
2
   1.9%
9
   2.3%
Not Hispanic or Latino
6
 100.0%
2
  66.7%
3
 100.0%
2
  66.7%
2
  66.7%
2
  40.0%
3
  75.0%
3
  37.5%
3
  42.9%
2
  50.0%
3
  60.0%
7
  50.0%
6
  85.7%
6
  42.9%
41
  71.9%
19
  55.9%
7
  46.7%
13
 100.0%
16
  66.7%
23
  85.2%
18
  94.7%
5
  62.5%
89
  86.4%
281
  72.8%
Unknown or Not Reported
0
   0.0%
1
  33.3%
0
   0.0%
1
  33.3%
1
  33.3%
3
  60.0%
1
  25.0%
5
  62.5%
4
  57.1%
2
  50.0%
2
  40.0%
7
  50.0%
1
  14.3%
7
  50.0%
14
  24.6%
15
  44.1%
8
  53.3%
0
   0.0%
8
  33.3%
3
  11.1%
0
   0.0%
1
  12.5%
12
  11.7%
96
  24.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 3 participants 3 participants 3 participants 3 participants 5 participants 4 participants 8 participants 7 participants 4 participants 5 participants 14 participants 7 participants 14 participants 57 participants 34 participants 15 participants 13 participants 24 participants 27 participants 19 participants 8 participants 103 participants 386 participants
Asian/Oriental
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
2
  14.3%
6
  10.5%
2
   5.9%
0
   0.0%
8
  61.5%
3
  12.5%
2
   7.4%
1
   5.3%
0
   0.0%
30
  29.1%
55
  14.2%
White/Caucasian
6
 100.0%
3
 100.0%
3
 100.0%
3
 100.0%
2
  66.7%
1
  20.0%
3
  75.0%
5
  62.5%
5
  71.4%
3
  75.0%
4
  80.0%
7
  50.0%
6
  85.7%
8
  57.1%
37
  64.9%
17
  50.0%
7
  46.7%
2
  15.4%
15
  62.5%
22
  81.5%
16
  84.2%
7
  87.5%
51
  49.5%
233
  60.4%
Black or African-American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.8%
0
   0.0%
0
   0.0%
2
  15.4%
0
   0.0%
1
   3.7%
1
   5.3%
0
   0.0%
8
   7.8%
15
   3.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.0%
2
   0.5%
Missing/Unknown
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
3
  60.0%
1
  25.0%
3
  37.5%
2
  28.6%
1
  25.0%
0
   0.0%
7
  50.0%
0
   0.0%
4
  28.6%
13
  22.8%
15
  44.1%
8
  53.3%
0
   0.0%
6
  25.0%
2
   7.4%
1
   5.3%
1
  12.5%
13
  12.6%
81
  21.0%
1.Primary Outcome
Title Phase 1: Dose Escalation-Maximum Tolerated Dose (MTD)
Hide Description MTD:Highest dose level at which <33% of participants experience dose-limiting toxicity (DLT) during Cycle1. DLT: >=Grade(G)3: - nonhematologic toxicity, - nausea/vomiting lasting >48hrs(uncontrolled by aggressive antiemetic), - diarrhea lasting >48hrs (unresponsive to antidiarrheal drug); G4 neutropenia lasting >7days; Febrile neutropenia (ANC<1000/mm^3 with body temperature=>38.3°C/sustained temperature >=38°C for >1hr; Thrombocytopenia G4/G3 with bleeding, required blood transfusion; Corneal disorder worsened by 1 grade or more; Increased phosphorus: >=9mg/dL or >=7mg/dL lasting for >=7days or phosphate lowering therapy[PLT] for 7days); Creatinine increase (>1.5×upper limit of normal [ULN]) lasting for >=7 days associated with serum phosphorus >5.5 mg/dL(PLT=7days)/calcium×phosphorus >55 mg/dL(PLT=7days); Hypercalcemia G2 for >7days or G3; Ectopic de novo calcification in soft tissues; >G2 DLT: prevented Cycle 1 completion, inability to start Cycle 2 within 2 weeks of schedule.
Time Frame Cycle 1 (21-day cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on DLT evaluable population that included all participants in Phase 1 Dose Escalation who had either experience a DLT during the first cycle of treatment or who had complete the first cycle with at least 80% of planned TAS-120 administered.
Arm/Group Title Phase 1: Dose Escalation: QOD Dosing Phase 1: Dose Escalation: QD Dosing
Hide Arm/Group Description:
Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 at 4 DLs from 8 to 36 mg orally every other day (QOD; Monday, Wednesday and Friday of each week) and participants with FGF/FGFR abnormalities received orally TAS-120 at 6 DLs from 56 mg to 240 mg QOD in a 21-day treatment cycle until disease progression, unacceptable toxicity, or any other discontinuation criterion was met (maximum exposure: 11 months).
Participants with or without FGF/FGFR gene abnormalities received a dose between 4 to 24 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, or any other discontinuation criterion was met (maximum exposure: 24 months).
Overall Number of Participants Analyzed 42 44
Measure Type: Number
Unit of Measure: Milligrams
NA [1]  20
[1]
MTD for QOD dosing was not determined as no DLTs were observed for TAS-120 up to 200 mg QOD as the highest dose level studied.
2.Primary Outcome
Title Phase 1: Dose Escalation-Recommended Phase 2 Dose (RP2D) of TAS-120
Hide Description RP2D was MTD or less. MTD: Highest dose level at which <33% of participants experience DLT) during Cycle1. DLT: >=Grade(G)3: - nonhematologic toxicity, - nausea/vomiting lasting >48hrs(uncontrolled by aggressive antiemetic), - diarrhea lasting >48hrs (unresponsive to antidiarrheal drug); G4 neutropenia lasting >7days; Febrile neutropenia (ANC<1000/mm^3 with body temperature=>38.3°C/sustained temperature >=38°C for >1hr; Thrombocytopenia G4/G3 with bleeding, required blood transfusion; Corneal disorder worsened by 1 grade or more; Increased phosphorus: >=9mg/dL or >=7mg/dL lasting for >=7days or phosphate lowering therapy[PLT] for 7days); Creatinine increase (>1.5×upper limit of normal [ULN]) lasting for >=7 days associated with serum phosphorus >5.5 mg/dL(PLT=7days)/calcium×phosphorus >55 mg/dL(PLT=7days); Hypercalcemia G2 for >7days or G3; Ectopic de novo calcification in soft tissues; >G2 DLT: prevented Cycle 1 completion, inability to start Cycle 2 within 2 weeks of schedule.
Time Frame Cycle 1 (21-day cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on DLT evaluable population that included all participants in Phase 1 Dose Escalation who had either experience a DLT during the first cycle of treatment or who had complete the first cycle with at least 80% of planned TAS-120 administered.
Arm/Group Title Phase 1: Dose Escalation: QOD Dosing Phase 1: Dose Escalation: QD Dosing
Hide Arm/Group Description:
Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 at 4 DLs from 8 to 36 mg orally every other day (QOD; Monday, Wednesday and Friday of each week) and participants with FGF/FGFR abnormalities received orally TAS-120 at 6 DLs from 56 mg to 240 mg QOD in a 21-day treatment cycle until disease progression, unacceptable toxicity, or any other discontinuation criterion was met (maximum exposure: 11 months).
Participants with or without FGF/FGFR gene abnormalities received a dose between 4 to 24 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, or any other discontinuation criterion was met (maximum exposure: 24 months).
Overall Number of Participants Analyzed 42 44
Measure Type: Number
Unit of Measure: Milligrams
NA [1]  20
[1]
MTD for QOD dosing was not determined as no DLTs were observed for TAS-120 up to 200 mg QOD as the highest dose level studied and thus no RP2D was determined.
3.Primary Outcome
Title Phase 1: Dose Expansion: Percentage of Participants With Objective Response
Hide Description Objective response was defined as proportion of participants who had achieved best overall response of partial response (PR) or complete response (CR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The CR was defined as a disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must had reduction in short axis to <10 millimeters (mm) and PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions. For Cohorts 1 to 6: Objective response was based on Independent Review Committee (IRC) and for pooled Sub-cohort: Objective response was based on investigator review.
Time Frame Up to approximately 50.5 months (through cut-off date 29-May-2021) for Cohorts 1 to 6; up to approximately 27.5 months (through cut-off date 30-Jun-2019) for pooled sub-cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy population included all participants who had received at least 1 dose of TAS-120. Data was planned to be collected and analyzed on pooled population of participants who received 16 mg of TAS-120 in the sub-cohorts 1and 2.
Arm/Group Title Phase 1: Dose Expansion Cohort 1 Phase 1: Dose Expansion: Cohort 2 Phase 1: Dose Expansion: Cohort 3 Phase 1: Dose Expansion: Cohort 4 Phase 1: Dose Expansion: Cohort 5 Phase 1: Dose Expansion: Cohort 6 Phase 1: Dose Expansion: Pooled Sub-cohort
Hide Arm/Group Description:
Participants with intra-hepatic or extrahepatic cholangiocarcinoma (iCCA or eCCA) harboring FGFR2 gene fusions or rearrangements and who were treated or not treated with prior FGFR inhibitors received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death
Participants with primary central nervous system (CNS) tumors harboring FGFR gene fusions or FGFR1 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with advanced urothelial carcinoma harboring FGFR3 gene fusions or FGFR3 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with breast or gastric cancer with harboring FGFR2 amplification received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with tumor types harboring FGFR gene fusions or activating mutations received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants who were not included in Cohorts 1 to 5 received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with iCCA and other tumor types who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 57 34 15 13 24 27 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
15.8
(7.5 to 27.9)
8.8
(1.9 to 23.7)
13.3
(1.7 to 40.5)
0
(0.0 to 24.7)
12.5
(2.7 to 32.4)
0
(0.0 to 12.8)
33.3
(16.5 to 54.0)
4.Primary Outcome
Title Phase 2: Percentage of Participants With Objective Response
Hide Description Objective response was defined as proportion of participants who had achieved best overall response of PR or CR per RECIST v1.1. CR was defined as a disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must had reduction in short axis to <10 mm and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. The Phase 2 evaluation of objective response was based on central independent CT/MRI image assessment.
Time Frame Up to approximately 37.5 months (through cut-off date 29-May-2021)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy population included all treated iCCA participants with confirmed FGFR2 gene fusions or other FGFR2 rearrangements who had received at least 1 dose of TAS-120.
Arm/Group Title Phase 2
Hide Arm/Group Description:
Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 103
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
41.7
(32.1 to 51.9)
5.Secondary Outcome
Title Phase 1: Dose Expansion: Duration of Response (DOR)
Hide Description A DOR was defined as the time (in months) from the first documentation of response (CR or PR) to the first documentation of objective progressive disease (PD) or death due to any cause, whichever occurred first. Participants who started subsequent anticancer therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy. For Cohorts 1 to 6: DOR was based on IRC and for Group 3, 4, 5, 6 and for pooled Sub-cohort: DOR was based on investigator review.
Time Frame Up to approximately 50.5 months (through cut-off date 29-May-2021) for Cohorts 1 to 6; up to approximately 27.5 months (through cut-off date 30-Jun-2019) for pooled sub-cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the subset of participants with PR or CR in efficacy population. Here, 'overall number of participants analyzed' signifies participants with available data for this outcome measure. Data was planned to be collected and analyzed on pooled population of participants who received 16 mg of TAS-120 in the sub-cohorts 1 and 2.
Arm/Group Title Phase 1: Dose Expansion Cohort 1 Phase 1: Dose Expansion: Cohort 2 Phase 1: Dose Expansion: Cohort 3 Phase 1: Dose Expansion: Cohort 4 Phase 1: Dose Expansion: Cohort 5 Phase 1: Dose Expansion: Cohort 6 Phase 1: Dose Expansion: Pooled Sub-cohort
Hide Arm/Group Description:
Participants with intra-hepatic or extrahepatic cholangiocarcinoma (iCCA or eCCA) harboring FGFR2 gene fusions or rearrangements and who were treated or not treated with prior FGFR inhibitors received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with primary central nervous system (CNS) tumors harboring FGFR gene fusions or FGFR1 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with advanced urothelial carcinoma harboring FGFR3 gene fusions or FGFR3 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with breast or gastric cancer with harboring FGFR2 amplification received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with tumor types harboring FGFR gene fusions or activating mutations received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants who were not included in Cohorts 1 to 5 received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with iCCA and other tumor types who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 9 2 2 0 3 0 9
Median (Full Range)
Unit of Measure: months
6.18
(2.8 to 10.6)
3.52
(2.8 to 4.3)
2.45
(1.4 to 3.4)
2.79
(2.0 to 4.1)
8.77
(3.5 to 20.8)
6.Secondary Outcome
Title Phase 2: Duration of Response (DOR)
Hide Description A DOR was defined as the time (in months) from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Participants who started subsequent anticancer therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy. Kaplan-Meier method was used for the analysis.
Time Frame Up to approximately 37.5 months (through cut-off date 29-May-2021)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the subset of participants with PR or CR in efficacy population. Here, 'overall number of participants analyzed' signifies participants with available data for this outcome measure.
Arm/Group Title Phase 2
Hide Arm/Group Description:
Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 43
Median (95% Confidence Interval)
Unit of Measure: months
8.31
(2.1 to 24.8)
7.Secondary Outcome
Title Phase 1: Dose Expansion: Disease Control Rate (DCR)
Hide Description A DCR was defined as the proportion of participants with objective evidence of CR, PR, or stable disease (SD), except that there was no requirement for a confirmation of an SD, if it is maintained for at least 6 weeks post treatment initiation. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes might had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the Baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taken as a reference the smallest sum diameters while on study. For Cohorts 1 to 6: DCR was based on IRC and for pooled Sub-cohort: DCR was based on investigator review.
Time Frame Up to approximately 50.5 months (through cut-off date 29-May-2021) for Cohorts 1 to 6; up to approximately 27.5 months (through cut-off date 30-Jun-2019) for pooled sub-cohort
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy population included all participants who had received at least 1 dose of TAS-120. Data was planned to be collected and analyzed on pooled population of participants who received 16 mg of TAS-120 in the sub-cohorts 1 and 2.
Arm/Group Title Phase 1: Dose Expansion Cohort 1 Phase 1: Dose Expansion: Cohort 2 Phase 1: Dose Expansion: Cohort 3 Phase 1: Dose Expansion: Cohort 4 Phase 1: Dose Expansion: Cohort 5 Phase 1: Dose Expansion: Cohort 6 Phase 1: Dose Expansion: Pooled Sub-cohort
Hide Arm/Group Description:
Participants with intra-hepatic or extrahepatic cholangiocarcinoma (iCCA or eCCA) harboring FGFR2 gene fusions or rearrangements and who were treated or not treated with prior FGFR inhibitors received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with primary central nervous system (CNS) tumors harboring FGFR gene fusions or FGFR1 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with advanced urothelial carcinoma harboring FGFR3 gene fusions or FGFR3 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with breast or gastric cancer with harboring FGFR2 amplification received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with tumor types harboring FGFR gene fusions or activating mutations received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants who were not included in Cohorts 1 to 5 received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with iCCA and other tumor types who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 57 34 15 13 24 27 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
66.7
(52.9 to 78.6)
23.5
(10.7 to 41.2)
33.3
(11.8 to 61.6)
38.5
(13.9 to 68.4)
54.2
(32.8 to 74.4)
22.2
(8.6 to 42.3)
66.7
(46.0 to 83.5)
8.Secondary Outcome
Title Phase 2: Disease Control Rate (DCR)
Hide Description A DCR was defined as the proportion of participants with objective evidence of CR, PR, or SD, except that there was no requirement for a confirmation of an SD response, if it is maintained for at least 6 weeks post treatment initiation. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes might had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the Baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taken as a reference the smallest sum diameters while on study. DCR was based on IRC.
Time Frame Up to approximately 37.5 months (through cut-off date 29-May-2021)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy population included all treated iCCA participants with confirmed FGFR2 gene fusions or other FGFR2 rearrangements who had received at least 1 dose of TAS-120.
Arm/Group Title Phase 2
Hide Arm/Group Description:
Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 103
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
82.5
(73.8 to 89.3)
9.Secondary Outcome
Title Phase 1: Dose Expansion: Progression-free Survival (PFS)
Hide Description A PFS was defined as the time (in months) from the day of the first dose to the date of first documented disease progression or death (due to any cause), whichever occurred first. Participants who died without a reported disease progression were considered to have progressed on the date of their death, participants who did not progress or die were censored on the date of their last tumor assessment, participants who had no on-study assessments and did not die were censored on the first dosing date, and participants who started any subsequent anti-cancer therapy without a prior reported progression were censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. PFS assessment per protocol was by IRC assessment for Cohorts 1 to 6 and for pooled Sub-cohort: PFS was based on investigator review.
Time Frame up to approximately 27.5 months (through cut-off date 30-Jun-2019)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy population included all participants who had received at least 1 dose of TAS-120. Data was planned to be collected and analyzed on pooled population of participants who received 16 mg of TAS-120 in the sub-cohorts 1 and 2.
Arm/Group Title Phase 1: Dose Expansion Cohort 1 Phase 1: Dose Expansion: Cohort 2 Phase 1: Dose Expansion: Cohort 3 Phase 1: Dose Expansion: Cohort 4 Phase 1: Dose Expansion: Cohort 5 Phase 1: Dose Expansion: Cohort 6 Phase 1: Dose Expansion: Pooled Sub-cohort
Hide Arm/Group Description:
Participants with intra-hepatic or extrahepatic cholangiocarcinoma (iCCA or eCCA) harboring FGFR2 gene fusions or rearrangements and who were treated or not treated with prior FGFR inhibitors received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with primary central nervous system (CNS) tumors harboring FGFR gene fusions or FGFR1 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with advanced urothelial carcinoma harboring FGFR3 gene fusions or FGFR3 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with breast or gastric cancer with harboring FGFR2 amplification received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with tumor types harboring FGFR gene fusions or activating mutations received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants who were not included in Cohorts 1 to 5 received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with iCCA and other tumor types who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 57 34 15 13 24 27 27
Median (95% Confidence Interval)
Unit of Measure: months
4.1
(2.7 to 6.9)
1.9
(1.3 to 4.9)
1.8
(1.3 to 4.7)
1.3
(0.9 to 4.1)
3.5
(1.7 to 6.8)
2.7
(1.4 to 2.7)
6.9
(4.6 to 10.8)
10.Secondary Outcome
Title Phase 2: Progression-free Survival (PFS)
Hide Description A PFS was defined as the time (in months) from the day of the first dose to the date of first objectively documented disease progression or death (any cause), whichever occurred first. Participants who had died without a reported disease progression were considered to have progressed on the date of their death, participants who did not progress or die were censored on the date of their last tumor assessment, participants who had no on-study assessments and did not die were censored on the first dosing date, and participants who started any subsequent anti-cancer therapy without a prior reported progression were censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. PFS was analyzed as using Kaplan-Meier estimate.
Time Frame Up to approximately 37.5 months (through cut-off date 29-May-2021)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy population included all treated iCCA participants with confirmed FGFR2 gene fusions or other FGFR2 rearrangements who had received at least 1 dose of TAS-120.
Arm/Group Title Phase 2
Hide Arm/Group Description:
Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 103
Median (95% Confidence Interval)
Unit of Measure: months
8.9
(6.7 to 11.0)
11.Secondary Outcome
Title Phase 1: Dose Expansion: Overall Survival (OS)
Hide Description An OS was defined as the time (in months) from the date of the first dose to the death date. In the absence of death confirmation or for participants alive as of the OS cut-off date, survival time was censored at the date of last study follow-up, or the cut-off date, whichever was earlier.
Time Frame up to approximately 27.5 months (through cut-off date 30-Jun-2019)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy population included all participants who had received at least 1 dose of TAS-120. Data was planned to be collected and analyzed on pooled population of participants who received 16 mg of TAS-120 in the sub-cohorts 1 and 2.
Arm/Group Title Phase 1: Dose Expansion Cohort 1 Phase 1: Dose Expansion: Cohort 2 Phase 1: Dose Expansion: Cohort 3 Phase 1: Dose Expansion: Cohort 4 Phase 1: Dose Expansion: Cohort 5 Phase 1: Dose Expansion: Cohort 6 Phase 1: Dose Expansion: Pooled Sub-cohort
Hide Arm/Group Description:
Participants with intra-hepatic or extrahepatic cholangiocarcinoma (iCCA or eCCA) harboring FGFR2 gene fusions or rearrangements and who were treated or not treated with prior FGFR inhibitors received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with primary central nervous system (CNS) tumors harboring FGFR gene fusions or FGFR1 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with advanced urothelial carcinoma harboring FGFR3 gene fusions or FGFR3 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with breast or gastric cancer with harboring FGFR2 amplification received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with tumor types harboring FGFR gene fusions or activating mutations received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants who were not included in Cohorts 1 to 5 received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with iCCA and other tumor types who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 57 34 15 13 24 27 27
Median (95% Confidence Interval)
Unit of Measure: months
11.4
(8.1 to 15.1)
11.8 [1] 
(5.5 to NA)
8.6 [2] 
(2.1 to NA)
5.8 [2] 
(4.6 to NA)
10.5 [2] 
(6.7 to NA)
7.2 [2] 
(5.6 to NA)
NA [3] 
(12.2 to NA)
[1]
Upper limit of 95% confidence interval (CI) was not estimable due to the smaller number of participants with events.
[2]
Upper limit of 95% CI was not estimable due to the smaller number of participants with events.
[3]
Median and upper limit of 95% CI was not estimable due to the smaller number of participants with events.
12.Secondary Outcome
Title Phase 2: Overall Survival (OS)
Hide Description An OS was defined as the time (in months) from the date of the first dose to the death date. In the absence of death confirmation or for participants alive as of the OS cut-off date, survival time was censored at the date of last study follow-up, or the cut-off date, whichever was earlier.
Time Frame Up to approximately 37.5 months (through cut-off date 29-May-2021)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy population included all treated iCCA participants with confirmed FGFR2 gene fusions or other FGFR2 rearrangements who had received at least 1 dose of TAS-120.
Arm/Group Title Phase 2
Hide Arm/Group Description:
Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 103
Median (95% Confidence Interval)
Unit of Measure: months
20.0
(16.4 to 24.6)
13.Secondary Outcome
Title Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits
Hide Description EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category.
Time Frame Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
Hide Outcome Measure Data
Hide Analysis Population Description
Patient-reported outcomes (PRO) Population that included all participants who had received TAS-120 treatment and had EQ-5D-3L assessment at Baseline and at least one subsequent post-baseline assessment. Here, 'number analyzed' = number of participants with available data for each specified category.
Arm/Group Title Phase 2
Hide Arm/Group Description:
Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 92
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline Number Analyzed 90 participants
No Problem
72
  80.0%
Some Problem
18
  20.0%
Extreme Problem
0
   0.0%
Cycle 2 Number Analyzed 81 participants
No Problem
60
  74.1%
Some Problem
20
  24.7%
Extreme Problem
1
   1.2%
Cycle 4 Number Analyzed 78 participants
No Problem
60
  76.9%
Some Problem
18
  23.1%
Extreme Problem
0
   0.0%
Cycle 7 Number Analyzed 65 participants
No Problem
51
  78.5%
Some Problem
14
  21.5%
Extreme Problem
0
   0.0%
Cycle 10 Number Analyzed 58 participants
No Problem
42
  72.4%
Some Problem
16
  27.6%
Extreme Problem
0
   0.0%
Cycle 13 Number Analyzed 47 participants
No Problem
32
  68.1%
Some Problem
15
  31.9%
Extreme Problem
0
   0.0%
Cycle 16 Number Analyzed 35 participants
No Problem
23
  65.7%
Some Problem
12
  34.3%
Extreme Problem
0
   0.0%
Cycle 19 Number Analyzed 28 participants
No Problem
16
  57.1%
Some Problem
12
  42.9%
Extreme Problem
0
   0.0%
Cycle 22 Number Analyzed 21 participants
No Problem
9
  42.9%
Some Problem
12
  57.1%
Extreme Problem
0
   0.0%
Cycle 25 Number Analyzed 12 participants
No Problem
9
  75.0%
Some Problem
2
  16.7%
Extreme Problem
1
   8.3%
Cycle 28 Number Analyzed 8 participants
No Problem
6
  75.0%
Some Problem
2
  25.0%
Extreme Problem
0
   0.0%
Cycle 31 Number Analyzed 3 participants
No Problem
3
 100.0%
Some Problem
0
   0.0%
Extreme Problem
0
   0.0%
Cycle 34 Number Analyzed 3 participants
No Problem
3
 100.0%
Some Problem
0
   0.0%
Extreme Problem
0
   0.0%
Cycle 37 Number Analyzed 3 participants
No Problem
2
  66.7%
Some Problem
1
  33.3%
Extreme Problem
0
   0.0%
Cycle 40 Number Analyzed 1 participants
No Problem
0
   0.0%
Some Problem
1
 100.0%
Extreme Problem
0
   0.0%
End of Treatment Number Analyzed 44 participants
No Problem
23
  52.3%
Some Problem
20
  45.5%
Extreme Problem
1
   2.3%
14.Secondary Outcome
Title Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits
Hide Description EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category.
Time Frame Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PRO population. Here, 'number analyzed' = number of participants with available data for each specified category.
Arm/Group Title Phase 2
Hide Arm/Group Description:
Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 92
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline Number Analyzed 90 participants
No Problem
82
  91.1%
Some Problem
8
   8.9%
Extreme Problem
0
   0.0%
Cycle 2 Number Analyzed 81 participants
No Problem
75
  92.6%
Some Problem
6
   7.4%
Extreme Problem
0
   0.0%
Cycle 4 Number Analyzed 78 participants
No Problem
70
  89.7%
Some Problem
7
   9.0%
Extreme Problem
1
   1.3%
Cycle 7 Number Analyzed 65 participants
No Problem
58
  89.2%
Some Problem
6
   9.2%
Extreme Problem
1
   1.5%
Cycle 10 Number Analyzed 58 participants
No Problem
52
  89.7%
Some Problem
5
   8.6%
Extreme Problem
1
   1.7%
Cycle 13 Number Analyzed 47 participants
No Problem
41
  87.2%
Some Problem
6
  12.8%
Extreme Problem
0
   0.0%
Cycle 16 Number Analyzed 35 participants
No Problem
30
  85.7%
Some Problem
4
  11.4%
Extreme Problem
1
   2.9%
Cycle 19 Number Analyzed 28 participants
No Problem
22
  78.6%
Some Problem
6
  21.4%
Extreme Problem
0
   0.0%
Cycle 22 Number Analyzed 21 participants
No Problem
18
  85.7%
Some Problem
3
  14.3%
Extreme Problem
0
   0.0%
Cycle 25 Number Analyzed 12 participants
No Problem
9
  75.0%
Some Problem
3
  25.0%
Extreme Problem
0
   0.0%
Cycle 28 Number Analyzed 8 participants
No Problem
8
 100.0%
Some Problem
0
   0.0%
Extreme Problem
0
   0.0%
Cycle 31 Number Analyzed 3 participants
No Problem
3
 100.0%
Some Problem
0
   0.0%
Extreme Problem
0
   0.0%
Cycle 34 Number Analyzed 3 participants
No Problem
3
 100.0%
Some Problem
0
   0.0%
Extreme Problem
0
   0.0%
Cycle 37 Number Analyzed 3 participants
No Problem
2
  66.7%
Some Problem
1
  33.3%
Extreme Problem
0
   0.0%
Cycle 40 Number Analyzed 1 participants
No Problem
1
 100.0%
Some Problem
0
   0.0%
Extreme Problem
0
   0.0%
End of Treatment Number Analyzed 43 participants
No Problem
34
  79.1%
Some Problem
8
  18.6%
Extreme Problem
1
   2.3%
15.Secondary Outcome
Title Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits
Hide Description EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category.
Time Frame Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PRO population. Here, 'number analyzed' = number of participants with available data for each specified category.
Arm/Group Title Phase 2
Hide Arm/Group Description:
Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 92
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline Number Analyzed 89 participants
No Problem
63
  70.8%
Some Problem
24
  27.0%
Extreme Problem
2
   2.2%
Cycle 2 Number Analyzed 81 participants
No Problem
47
  58.0%
Some Problem
32
  39.5%
Extreme Problem
2
   2.5%
Cycle 4 Number Analyzed 78 participants
No Problem
50
  64.1%
Some Problem
27
  34.6%
Extreme Problem
1
   1.3%
Cycle 7 Number Analyzed 65 participants
No Problem
43
  66.2%
Some Problem
20
  30.8%
Extreme Problem
2
   3.1%
Cycle 10 Number Analyzed 58 participants
No Problem
34
  58.6%
Some Problem
23
  39.7%
Extreme Problem
1
   1.7%
Cycle 13 Number Analyzed 47 participants
No Problem
28
  59.6%
Some Problem
19
  40.4%
Extreme Problem
0
   0.0%
Cycle 16 Number Analyzed 35 participants
No Problem
20
  57.1%
Some Problem
14
  40.0%
Extreme Problem
1
   2.9%
Cycle 19 Number Analyzed 28 participants
No Problem
15
  53.6%
Some Problem
12
  42.9%
Extreme Problem
1
   3.6%
Cycle 22 Number Analyzed 21 participants
No Problem
7
  33.3%
Some Problem
14
  66.7%
Extreme Problem
0
   0.0%
Cycle 25 Number Analyzed 12 participants
No Problem
4
  33.3%
Some Problem
7
  58.3%
Extreme Problem
1
   8.3%
Cycle 28 Number Analyzed 8 participants
No Problem
3
  37.5%
Some Problem
5
  62.5%
Extreme Problem
0
   0.0%
Cycle 31 Number Analyzed 3 participants
No Problem
1
  33.3%
Some Problem
2
  66.7%
Extreme Problem
0
   0.0%
Cycle 34 Number Analyzed 3 participants
No Problem
2
  66.7%
Some Problem
1
  33.3%
Extreme Problem
0
   0.0%
Cycle 37 Number Analyzed 3 participants
No Problem
0
   0.0%
Some Problem
3
 100.0%
Extreme Problem
0
   0.0%
Cycle 40 Number Analyzed 1 participants
No Problem
0
   0.0%
Some Problem
1
 100.0%
Extreme Problem
0
   0.0%
End of Treatment Number Analyzed 44 participants
No Problem
16
  36.4%
Some Problem
25
  56.8%
Extreme Problem
3
   6.8%
16.Secondary Outcome
Title Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits
Hide Description EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category.
Time Frame Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PRO population. Here, 'number analyzed' = number of participants with available data for each specified category.
Arm/Group Title Phase 2
Hide Arm/Group Description:
Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 92
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline Number Analyzed 90 participants
No Problem
42
  46.7%
Some Problem
47
  52.2%
Extreme Problem
1
   1.1%
Cycle 2 Number Analyzed 81 participants
No Problem
45
  55.6%
Some Problem
35
  43.2%
Extreme Problem
1
   1.2%
Cycle 4 Number Analyzed 78 participants
No Problem
40
  51.3%
Some Problem
36
  46.2%
Extreme Problem
2
   2.6%
Cycle 7 Number Analyzed 66 participants
No Problem
36
  54.5%
Some Problem
29
  43.9%
Extreme Problem
1
   1.5%
Cycle 10 Number Analyzed 58 participants
No Problem
30
  51.7%
Some Problem
26
  44.8%
Extreme Problem
2
   3.4%
Cycle 13 Number Analyzed 47 participants
No Problem
23
  48.9%
Some Problem
22
  46.8%
Extreme Problem
2
   4.3%
Cycle 16 Number Analyzed 35 participants
No Problem
13
  37.1%
Some Problem
19
  54.3%
Extreme Problem
3
   8.6%
Cycle 19 Number Analyzed 28 participants
No Problem
13
  46.4%
Some Problem
15
  53.6%
Extreme Problem
0
   0.0%
Cycle 22 Number Analyzed 21 participants
No Problem
6
  28.6%
Some Problem
14
  66.7%
Extreme Problem
1
   4.8%
Cycle 25 Number Analyzed 12 participants
No Problem
3
  25.0%
Some Problem
9
  75.0%
Extreme Problem
0
   0.0%
Cycle 28 Number Analyzed 8 participants
No Problem
2
  25.0%
Some Problem
5
  62.5%
Extreme Problem
1
  12.5%
Cycle 31 Number Analyzed 3 participants
No Problem
2
  66.7%
Some Problem
1
  33.3%
Extreme Problem
0
   0.0%
Cycle 34 Number Analyzed 3 participants
No Problem
3
 100.0%
Some Problem
0
   0.0%
Extreme Problem
0
   0.0%
Cycle 37 Number Analyzed 3 participants
No Problem
2
  66.7%
Some Problem
1
  33.3%
Extreme Problem
0
   0.0%
Cycle 40 Number Analyzed 1 participants
No Problem
0
   0.0%
Some Problem
1
 100.0%
Extreme Problem
0
   0.0%
End of Treatment Number Analyzed 44 participants
No Problem
12
  27.3%
Some Problem
27
  61.4%
Extreme Problem
5
  11.4%
17.Secondary Outcome
Title Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits
Hide Description EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category.
Time Frame Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PRO population. Here, 'number analyzed' = number of participants with available data for each specified category.
Arm/Group Title Phase 2
Hide Arm/Group Description:
Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 92
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline Number Analyzed 89 participants
No Problem
64
  71.9%
Some Problem
25
  28.1%
Extreme Problem
0
   0.0%
Cycle 2 Number Analyzed 81 participants
No Problem
66
  81.5%
Some Problem
15
  18.5%
Extreme Problem
0
   0.0%
Cycle 4 Number Analyzed 78 participants
No Problem
63
  80.8%
Some Problem
14
  17.9%
Extreme Problem
1
   1.3%
Cycle 7 Number Analyzed 65 participants
No Problem
48
  73.8%
Some Problem
15
  23.1%
Extreme Problem
2
   3.1%
Cycle 10 Number Analyzed 58 participants
No Problem
44
  75.9%
Some Problem
12
  20.7%
Extreme Problem
2
   3.4%
Cycle 13 Number Analyzed 47 participants
No Problem
36
  76.6%
Some Problem
11
  23.4%
Extreme Problem
0
   0.0%
Cycle 16 Number Analyzed 35 participants
No Problem
26
  74.3%
Some Problem
8
  22.9%
Extreme Problem
1
   2.9%
Cycle 19 Number Analyzed 28 participants
No Problem
21
  75.0%
Some Problem
6
  21.4%
Extreme Problem
1
   3.6%
Cycle 22 Number Analyzed 21 participants
No Problem
13
  61.9%
Some Problem
8
  38.1%
Extreme Problem
0
   0.0%
Cycle 25 Number Analyzed 12 participants
No Problem
8
  66.7%
Some Problem
4
  33.3%
Extreme Problem
0
   0.0%
Cycle 28 Number Analyzed 8 participants
No Problem
5
  62.5%
Some Problem
3
  37.5%
Extreme Problem
0
   0.0%
Cycle 31 Number Analyzed 3 participants
No Problem
2
  66.7%
Some Problem
1
  33.3%
Extreme Problem
0
   0.0%
Cycle 34 Number Analyzed 3 participants
No Problem
2
  66.7%
Some Problem
1
  33.3%
Extreme Problem
0
   0.0%
Cycle 37 Number Analyzed 3 participants
No Problem
1
  33.3%
Some Problem
2
  66.7%
Extreme Problem
0
   0.0%
Cycle 40 Number Analyzed 1 participants
No Problem
0
   0.0%
Some Problem
1
 100.0%
Extreme Problem
0
   0.0%
End of Treatment Number Analyzed 44 participants
No Problem
22
  50.0%
Some Problem
19
  43.2%
Extreme Problem
3
   6.8%
18.Secondary Outcome
Title Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits
Hide Description EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. A vertical VAS allows the participants to indicate their health state that day, and ranged from 0 (worst imaginable) to 100 (best imaginable), with higher scores indicating better health state.
Time Frame Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PRO population. Here, 'number analyzed' = number of participants with available data for each specified category.
Arm/Group Title Phase 2
Hide Arm/Group Description:
Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 92
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 88 participants
71.72  (20.307)
Change at Cycle 2 Number Analyzed 77 participants
-0.73  (19.409)
Change at Cycle 4 Number Analyzed 74 participants
-1.04  (23.984)
Change at Cycle 7 Number Analyzed 62 participants
-1.82  (29.984)
Change at Cycle 10 Number Analyzed 54 participants
0.40  (30.428)
Change at Cycle 13 Number Analyzed 45 participants
4.76  (26.585)
Change at Cycle 16 Number Analyzed 33 participants
-1.71  (34.417)
Change at Cycle 19 Number Analyzed 27 participants
1.76  (25.155)
Change at Cycle 22 Number Analyzed 20 participants
1.85  (31.707)
Change at Cycle 25 Number Analyzed 11 participants
-0.82  (45.828)
Change at Cycle 28 Number Analyzed 8 participants
-1.85  (40.912)
Change at Cycle 31 Number Analyzed 3 participants
18.17  (17.280)
Change at Cycle 34 Number Analyzed 3 participants
19.00  (19.313)
Change at Cycle 37 Number Analyzed 3 participants
15.17  (21.624)
Change at Cycle 40 Number Analyzed 1 participants
15.00
End of Treatment Number Analyzed 41 participants
-8.89  (26.272)
19.Secondary Outcome
Title Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints
Hide Description EORTC QLQ-C30 is a cancer-specific instrument that contains 30 questions for evaluation of new chemotherapy & assessment of participant reported outcome. EORTC QLQ-C30 included global health status/quality of life (GHS/QOL), functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from QLQ-C30 are 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale & are 7-point scale (1/Very Poor to 7/Excellent). GHS total score is calculated as ([{Q29+Q30}/2]-1)/6*100. Answers are converted into grading scale, with values between 0 (worse outcome) to100 (best outcome). High score represents a favorable outcome with best quality of life for participant.
Time Frame Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PRO population. Here, 'number analyzed' = number of participants with available data for each specified category.
Arm/Group Title Phase 2
Hide Arm/Group Description:
Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 92
Mean (Standard Deviation)
Unit of Measure: score on scale
Baseline Number Analyzed 91 participants
70.1  (19.41)
Change at Cycle 2 Number Analyzed 83 participants
-1.0  (22.02)
Change at Cycle 4 Number Analyzed 79 participants
0.4  (20.62)
Change at Cycle 7 Number Analyzed 65 participants
-0.5  (21.64)
Change at Cycle 10 Number Analyzed 58 participants
1.9  (22.84)
Change at Cycle 13 Number Analyzed 48 participants
0.9  (21.49)
Change at Cycle 16 Number Analyzed 27 participants
2.5  (18.61)
Change at Cycle 19 Number Analyzed 15 participants
-1.7  (17.31)
Change at Cycle 22 Number Analyzed 11 participants
-8.3  (22.05)
Change at Cycle 25 Number Analyzed 7 participants
-4.8  (21.44)
Change at Cycle 28 Number Analyzed 4 participants
-6.3  (12.50)
Change at Cycle 31 Number Analyzed 1 participants
41.7
Change at Cycle 34 Number Analyzed 1 participants
41.7
End of Treatment Number Analyzed 30 participants
-7.5  (23.30)
20.Secondary Outcome
Title Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs)
Hide Description An AE was defined as any untoward medical condition that occurred in a participant from the time the informed consent form (ICF) was signed and does not necessarily had a causal relationship with the use of the product. An SAE was an AE that falls into one or more of the following categories: a. resulted in death, b. was life threatening, c. required inpatient hospitalization or prolongation of existing hospitalization, d. resulted in persistent or significant disability or incapacity, e. was a congenital anomaly/birth defect, f. other important medical event.
Time Frame From the first dose up to approximately 50.5 months (through cut-off date 29-May-2021)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population (all treated participants) included all participants who had received at least 1 dose of TAS-120.
Arm/Group Title Phase 1: Dose Expansion Cohort 1 Phase 1: Dose Expansion: Cohort 2 Phase 1: Dose Expansion: Cohort 3 Phase 1: Dose Expansion: Cohort 4 Phase 1: Dose Expansion: Cohort 5 Phase 1: Dose Expansion: Cohort 6 Phase 1: Dose Expansion: Sub-cohort 1 Phase 1: Dose Expansion: Sub-cohort 2
Hide Arm/Group Description:
Participants with intra-hepatic or extrahepatic cholangiocarcinoma (iCCA or eCCA) harboring FGFR2 gene fusions or rearrangements and who were treated or not treated with prior FGFR inhibitors received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with primary central nervous system (CNS) tumors harboring FGFR gene fusions or FGFR1 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with advanced urothelial carcinoma harboring FGFR3 gene fusions or FGFR3 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with breast or gastric cancer with harboring FGFR2 amplification received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with tumor types harboring FGFR gene fusions or activating mutations received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants who were not included in Cohorts 1 to 5 received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with iCCA who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Participants with other tumor types who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 57 34 15 13 24 27 19 8
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
57
 100.0%
34
 100.0%
15
 100.0%
13
 100.0%
23
  95.8%
26
  96.3%
18
  94.7%
5
  62.5%
SAEs
27
  47.4%
13
  38.2%
10
  66.7%
9
  69.2%
13
  54.2%
14
  51.9%
0
   0.0%
0
   0.0%
21.Secondary Outcome
Title Phase 2: Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs)
Hide Description An AE was defined as any untoward medical condition that occurs in a participant from the time the informed consent form (ICF) was signed and does not necessarily had a causal relationship with the use of the product. An SAE was an AE that falls into one or more of the following categories: a. resulted in death, b. was life threatening, c. required inpatient hospitalization or prolongation of existing hospitalization, d. resulted in persistent or significant disability or incapacity, e. was a congenital anomaly/birth defect, f. other important medical event.
Time Frame From the first dose up to approximately 37.5 months (through cut-off date 29-May-2021)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population (all treated participants) included all participants who had received at least 1 dose of TAS-120.
Arm/Group Title Phase 2
Hide Arm/Group Description:
Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed 103
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
103
 100.0%
SAEs
42
  40.8%
Time Frame From the first dose administration up to approximately up to 59.5 months for Phase 1 Dose escalation; up to 50.5 months for Phase 1 Dose expansion Cohorts and up to 37.5 months for Phase 2
Adverse Event Reporting Description Safety Population (all treated participants) included all participants who had received at least 1 dose of TAS-120. MedDRA version 17.0 for Phase 1 and MedDRA version 22.0 for Phase 2. Safety analysis were done based on data cut-off dates: 12 July 2019 for Phase 1 Dose Escalation, 29-May-2021 for Phase 1 Dose Expansion and Phase 2.
 
Arm/Group Title Phase 1: Dose Escalation: QOD Dosing: 8 mg Phase 1: Dose Escalation: QOD Dosing: 16 mg Phase 1: Dose Escalation: QOD Dosing: 24 mg Phase 1: Dose Escalation: QOD Dosing: 36 mg Phase 1: Dose Escalation: QOD Dosing: 56 mg Phase 1: Dose Escalation: QOD Dosing: 80 mg Phase 1: Dose Escalation: QOD Dosing: 120 mg Phase 1: Dose Escalation: QOD Dosing: 160 mg Phase 1: Dose Escalation: QOD Dosing: 200 mg Phase 1: Dose Escalation: QD Dosing: 4 mg Phase 1: Dose Escalation: QD Dosing: 8 mg Phase 1: Dose Escalation: QD Dosing: 16 mg Phase 1: Dose Escalation: QD Dosing: 20 mg Phase 1: Dose Escalation: QD Dosing: 24 mg Phase 1: Dose Expansion Cohort 1 Phase 1: Dose Expansion: Cohort 2 Phase 1: Dose Expansion: Cohort 3 Phase 1: Dose Expansion: Cohort 4 Phase 1: Dose Expansion: Cohort 5 Phase 1: Dose Expansion: Cohort 6 Phase 1: Dose Expansion: Sub-cohort 2 Phase 1: Dose Expansion: Sub-cohort 1 Phase 2
Hide Arm/Group Description Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 8 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 16 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 24 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 36 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with FGF/FGFR gene abnormalities received orally TAS-120 56 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with FGF/FGFR gene abnormalities received orally TAS-120 80 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with FGF/FGFR gene abnormalities received orally TAS-120 120 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with FGF/FGFR gene abnormalities received orally TAS-120 160 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with FGF/FGFR gene abnormalities received orally TAS-120 200 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received a dose between 4 mg orally once daily (QD) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received a dose between 8 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received a dose between 16 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received a dose between 20 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with or without FGF/FGFR gene abnormalities received a dose between 24 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. Participants with intra-hepatic or extrahepatic cholangiocarcinoma (iCCA or eCCA) harboring FGFR2 gene fusions or rearrangements and who were treated or not treated with prior FGFR inhibitors received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death (maximum exposure: 33.5 months). Participants with primary central nervous system (CNS) tumors harboring FGFR gene fusions or FGFR1 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death (maximum exposure: 28.5 months). Participants with advanced urothelial carcinoma harboring FGFR3 gene fusions or FGFR3 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death (maximum exposure: 9.6 months). Participants with breast or gastric cancer with harboring FGFR2 amplification received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death (maximum exposure: 5.5 months). Participants with tumor types harboring FGFR gene fusions or activating mutations received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death (maximum exposure: 42.5 months). Participants who were not included in Cohorts 1 to 5 received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death (maximum exposure: 11 months). Participants with other tumor types who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death (maximum exposure: 45.5 months). Participants with iCCA who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death (maximum exposure: 28 months). Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death (maximum duration: 30 months).
All-Cause Mortality
Phase 1: Dose Escalation: QOD Dosing: 8 mg Phase 1: Dose Escalation: QOD Dosing: 16 mg Phase 1: Dose Escalation: QOD Dosing: 24 mg Phase 1: Dose Escalation: QOD Dosing: 36 mg Phase 1: Dose Escalation: QOD Dosing: 56 mg Phase 1: Dose Escalation: QOD Dosing: 80 mg Phase 1: Dose Escalation: QOD Dosing: 120 mg Phase 1: Dose Escalation: QOD Dosing: 160 mg Phase 1: Dose Escalation: QOD Dosing: 200 mg Phase 1: Dose Escalation: QD Dosing: 4 mg Phase 1: Dose Escalation: QD Dosing: 8 mg Phase 1: Dose Escalation: QD Dosing: 16 mg Phase 1: Dose Escalation: QD Dosing: 20 mg Phase 1: Dose Escalation: QD Dosing: 24 mg Phase 1: Dose Expansion Cohort 1 Phase 1: Dose Expansion: Cohort 2 Phase 1: Dose Expansion: Cohort 3 Phase 1: Dose Expansion: Cohort 4 Phase 1: Dose Expansion: Cohort 5 Phase 1: Dose Expansion: Cohort 6 Phase 1: Dose Expansion: Sub-cohort 2 Phase 1: Dose Expansion: Sub-cohort 1 Phase 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)      0/3 (0.00%)      0/3 (0.00%)      0/3 (0.00%)      0/3 (0.00%)      0/5 (0.00%)      1/4 (25.00%)      0/8 (0.00%)      2/7 (28.57%)      0/4 (0.00%)      0/5 (0.00%)      2/14 (14.29%)      1/7 (14.29%)      1/14 (7.14%)      40/57 (70.18%)      22/34 (64.71%)      12/15 (80.00%)      11/13 (84.62%)      15/24 (62.50%)      17/27 (62.96%)      1/8 (12.50%)      9/19 (47.37%)      58/103 (56.31%)    
Hide Serious Adverse Events
Phase 1: Dose Escalation: QOD Dosing: 8 mg Phase 1: Dose Escalation: QOD Dosing: 16 mg Phase 1: Dose Escalation: QOD Dosing: 24 mg Phase 1: Dose Escalation: QOD Dosing: 36 mg Phase 1: Dose Escalation: QOD Dosing: 56 mg Phase 1: Dose Escalation: QOD Dosing: 80 mg Phase 1: Dose Escalation: QOD Dosing: 120 mg Phase 1: Dose Escalation: QOD Dosing: 160 mg Phase 1: Dose Escalation: QOD Dosing: 200 mg Phase 1: Dose Escalation: QD Dosing: 4 mg Phase 1: Dose Escalation: QD Dosing: 8 mg Phase 1: Dose Escalation: QD Dosing: 16 mg Phase 1: Dose Escalation: QD Dosing: 20 mg Phase 1: Dose Escalation: QD Dosing: 24 mg Phase 1: Dose Expansion Cohort 1 Phase 1: Dose Expansion: Cohort 2 Phase 1: Dose Expansion: Cohort 3 Phase 1: Dose Expansion: Cohort 4 Phase 1: Dose Expansion: Cohort 5 Phase 1: Dose Expansion: Cohort 6 Phase 1: Dose Expansion: Sub-cohort 2 Phase 1: Dose Expansion: Sub-cohort 1 Phase 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/6 (16.67%)      0/3 (0.00%)      1/3 (33.33%)      1/3 (33.33%)      1/3 (33.33%)      2/5 (40.00%)      4/4 (100.00%)      7/8 (87.50%)      4/7 (57.14%)      0/4 (0.00%)      1/5 (20.00%)      9/14 (64.29%)      3/7 (42.86%)      6/14 (42.86%)      27/57 (47.37%)      13/34 (38.24%)      10/15 (66.67%)      9/13 (69.23%)      13/24 (54.17%)      14/27 (51.85%)      0/8 (0.00%)      0/19 (0.00%)      42/103 (40.78%)    
Blood and lymphatic system disorders                                               
Anaemia  1  0/6 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/4 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0/14 (0.00%)  0 0/7 (0.00%)  0 0/14 (0.00%)  0 1/57 (1.75%)  2 0/34 (0.00%)  0 0/15 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 1/27 (3.70%)  2 0/8 (0.00%)  0 0/19 (0.00%)  0 1/103 (0.97%)  3
Cardiac disorders                                               
Acute myocardial infarction  1  0/6 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/4 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/14 (0.00%)  0 0/7 (0.00%)  0 0/14 (0.00%)  0 0/57 (0.00%)  0 0/34 (0.00%)  0 0/15 (0.00%)  0 0/13 (0.00%)  0 1/24 (4.17%)  1 0/27 (0.00%)  0 0/8 (0.00%)  0 0/19 (0.00%)  0 0/103 (0.00%)  0
Atrial fibrillation  1  0/6 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/4 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/14 (0.00%)  0 0/7 (0.00%)  0 0/14 (0.00%)  0 1/57 (1.75%)  1 0/34 (0.00%)  0 0/15 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 0/27 (0.00%)  0 0/8 (0.00%)  0 0/19 (0.00%)  0 0/103 (0.00%)  0
Ventricular tachycardia  1  0/6 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/4 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/14 (0.00%)  0 0/7 (0.00%)  0 0/14 (0.00%)  0 0/57 (0.00%)  0 1/34 (2.94%)  1 0/15 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 0/27 (0.00%)  0 0/8 (0.00%)  0 0/19 (0.00%)  0 0/103 (0.00%)  0
Eye disorders                                               
Cataract  1  0/6 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/4 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/14 (0.00%)  0 0/7 (0.00%)  0 0/14 (0.00%)  0 0/57 (0.00%)  0 0/34 (0.00%)  0 0/15 (0.00%)  0 0/13 (0.00%)  0 1/24 (4.17%)  2 0/27 (0.00%)  0 0/8 (0.00%)  0 0/19 (0.00%)  0 0/103 (0.00%)  0
Ocular ischaemic syndrome  1  0/6 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/4 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/14 (0.00%)  0 0/7 (0.00%)  0 0/14 (0.00%)  0 1/57 (1.75%)  1 0/34 (0.00%)  0 0/15 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 0/27 (0.00%)  0 0/8 (0.00%)  0 0/19 (0.00%)  0 0/103 (0.00%)  0
Papilloedema  1  0/6 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/4 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/14 (0.00%)  0 0/7 (0.00%)  0 0/14 (0.00%)  0 0/57 (0.00%)  0 0/34 (0.00%)  0 0/15 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 1/27 (3.70%)  1 0/8 (0.00%)  0 0/19 (0.00%)  0 0/103 (0.00%)  0
Retinal detachment  1  0/6 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/4 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/14 (0.00%)  0 0/7 (0.00%)  0 0/14 (0.00%)  0 0/57 (0.00%)  0 0/34 (0.00%)  0 0/15 (0.00%)  0 0/13 (0.00%)  0 1/24 (4.17%)  1 0/27 (0.00%)  0 0/8 (0.00%)  0 0/19 (0.00%)  0 0/103 (0.00%)  0
Gastrointestinal disorders                                               
Abdominal pain  1  0/6 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/4 (0.00%)  0 2/8 (25.00%)  2 1/7 (14.29%)  1 0/4 (0.00%)  0 0/5 (0.00%)  0 1/14 (7.14%)  1 0/7 (0.00%)  0 0/14 (0.00%)  0 3/57 (5.26%)  3 0/34 (0.00%)  0 0/15 (0.00%)  0 1/13 (7.69%)  1 1/24 (4.17%)  2 0/27 (0.00%)  0 0/8 (0.00%)  0 0/19 (0.00%)  0 1/103 (0.97%)  1
Abdominal pain upper  1  0/6 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/4 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/14 (0.00%)  0 0/7 (0.00%)  0 0/14 (0.00%)  0 1/57 (1.75%)  1 0/34 (0.00%)  0 0/15 (0.00%)  0 0/13 (0.00%)  0 1/24 (4.17%)  1 0/27 (0.00%)  0 0/8 (0.00%)  0 0/19 (0.00%)  0 0/103 (0.00%)  0
Ascites  1  0/6 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/4 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/14 (0.00%)  0 0/7 (0.00%)  0 0/14 (0.00%)  0 0/57 (0.00%)  0 0/34 (0.00%)  0 0/15 (0.00%)  0 1/13 (7.69%)  1 0/24 (0.00%)  0 0/27 (0.00%)  0 0/8 (0.00%)  0 0/19 (0.00%)  0 4/103 (3.88%)  4
Colitis  1  0/6 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/4 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/14 (0.00%)  0 0/7 (0.00%)  0 0/14 (0.00%)  0 2/57 (3.51%)  2 0/34 (0.00%)  0 0/15 (0.00%)  0 0/13 (0.00%)  0 0/24 (0.00%)  0 0/27 (0.00%)  0 0/8 (0.00%)  0 0/19 (0.00%)  0 0/103 (0.00%)  0
Colonic pseudo-obstruction  1  0/6 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/4 (0.00%)  0 0/8 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/14 (0.00%)  0 0/7 (0.00%)