Phase 1/2 Study of TAS-120 in Patients With Advanced Solid Tumors Harboring FGF/FGFR Aberrations
Phase: PHASE1
Conditions: Cholangiocarcinoma, Urothelial Cancer, Advanced and Metastatic Cancer Patients With Tumors Harboring FGF/FGFR Tumors, Primary CNS Tumors, Breast Cancer, Gastric Cancer
Sponsor: Taiho Oncology, Inc.

PHASE 1/2 STUDY OF TAS-120 IN PATIENTS WITH
ADVANCED SOLID TUMORS HARBORING FGF/FGFR ABERRATIONS 
TAS-120
Protocol No.: TPU-TAS-120-101
IND No.: 
 (TAS-120)
EudraCT No.: 2013-004810-16
09 December 2013
PROTOCOL AMENDMENT 1: 31 January 2014
PROTOCOL AMENDMENT 2: 22 September 2014
PROTOCOL AMENDMENT 3: 19 February 2016
PROTOCOL AMENDMENT 4: 15 May 2017
PROTOCOL AMENDMENT 5: 29 August 2017
PROTOCOL AMENDMENT 6: 31 January 2018
PROTOCOL AMENDMENT 7: 28 September 2018
PROTOCOL AMENDMENT 8: 12 April 2019
PROTOCOL AMENDMENT 9: 01 August 2019
This multinational study will be conducted under the sponsorship of Taiho Pharmaceutical Co., 
Ltd. for sites in Japan and Taiho Oncology, Inc. for sites in the rest of the world:
Taiho Pharmaceutical Co., Ltd
1-27 Kandanishiki-Cho
Chiyoda-ku, Tokyo, 101-8444, Japan
Taiho Oncology, Inc.
101-Carnegie Center, Suite 101 
Princeton, NJ 08540, USA
This clinical study will be conducted in accordance with International Council for Harmonisation 
Good Clinical Practice Guidelines.
CONFIDENTIAL
The information contained in this document is the property of Taiho Oncology, Inc. (TOI) and Taiho 
Pharmaceutical Co., Ltd. (TPC). This document contains strictly confidential information and no part 
of this document may be published or disclosed, except as necessary to obtain consent from persons 
who are considering participation in the study, without the prior written approval of TOI and TPC.
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SUMMARY OF CHANGES 
The following table summarizes substantive changes made to the protocol in Amendment 9; all 
changes shown here were also incorporated into the Study Synopsis as appropriate. In addition, 
minor administrative changes (not summarized in this table) were made throughout the 
document, including updating of the headers and cover page and correction of minor 
typographical or formatting errors.
Section
Description of Change 
Brief Rationale
Section 7.2.1
Inclusion Criteria
Section 9.1
Pre-screening of 
Tumor Tissue Sample 
for FGFR2 Gene 
Fusions or 
Other FGFR2 
Rearrangements in 
Patients with iCCA 
(Phase 2 Only)
Criterion #3 (b) was amended as follows:
i. Patient has histologically or 
cytologically confirmed, locally advanced, 
metastatic, unresectable iCCA harboring 
FGFR2 gene fusions or other FGFR2 
rearrangements based on results from either 
of the following (see Section 9.1 for 
details): 
a. Testing by Foundation Medicine:
i.
As part of study pre-screening; or
ii. Previously tested by Foundation 
Medicine; in this case, it is requested 
that tumor tissue should be provided to 
Foundation Medicine if available. 
b. Local laboratory testing using next 
generation sequencing [NGS], fluorescence 
in situ hybridization [FISH], or other 
assays that can determine FGFR2 gene 
fusions or other FGFR2 rearrangements on 
tumor tissues or from ctDNA; patients 
enrolled on this basis must have available 
tumor tissues from either archival samples 
or fresh tumor biopsy submitted to 
Foundation Medicine for confirmation of 
FGFR2 gene fusion or other FGFR2 
rearrangements. It is requested that patients 
enrolled on this basis provide tumor tissues 
to Foundation Medicine, if available from 
either archival samples or fresh tumor 
biopsy.
In order to facilitate enrollment of 
patients, the requirement that 
FGFR2 rearrangements be centrally 
confirmed prior to enrollment was 
removed in the entry criteria and 
throughout the protocol.
Section 12.3.3
Determination of 
Sample Size 
(Phase 2)
Text was amended as follows:
Approximately 100 iCCA patients with 
Foundation Medicine confirmed FGFR2 
gene fusions or other FGFR2
rearrangements will be treated.
In order to facilitate enrollment of 
patients, the requirement that 
FGFR2 rearrangements be centrally 
confirmed prior to enrollment was 
removed.
Section 12.3.3
Determination of 
Sample Size 
(Phase 2)
The following text was added:
After approximately 100 patients have been 
enrolled, if the proportion of patients at 
sites in Japan is <10% of the total 
population, enrollment may continue in 
Japan until the proportion is ≥10%.
Added condition to ensure the 
ability to enroll a suitable number of 
patients at sites in Japan.

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Section
Description of Change 
Brief Rationale
Section 12.4
Interim Analyses
Text was amended as follows:
Interim reviews of safety data from the 
Phase 2 portion will be performed 
approximately every 3 months throughout 
the study, until the last patient in the Phase 
2 portion has been treated and followed for 
at least 4 cycles until the interim analysis 
cut-off.
The schedule of safety reviews was 
adjusted consistent with the 
institution of a formal interim 
analysis of efficacy as described 
below.
Section 12.4
Interim Analyses
The following text was added:
A formal interim analysis will be 
performed when approximately 70% all 
treated patients had 6 months of follow-up. 
Two-sided 95% CI and 99% CI will both 
be provided for the primary efficacy 
analysis.  A safety analysis will also be 
performed at this time, and the results will 
be shared with the SRC.
An interim analysis of efficacy has 
been added.
Appendix G
Supplemental 
Requirements for 
Japan Only
The anticipated date of study completion was 
amended from April 2020 to April 2021.
Revised estimate based on study 
progress and expected enrollment 
rate.

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1.
SYNOPSIS
Title of Study:
PHASE 1/2 STUDY OF TAS-120 IN PATIENTS WITH ADVANCED SOLID TUMORS HARBORING 
FGF/FGFR ABERRATIONS
Protocol Number:
TPU-TAS-120-101
Phase:
1 / 2
Indication:
Advanced solid tumors 
Background:
Activating fibroblast growth factor receptor (FGFR) gene abnormalities are reported in various cancers 
including non-small cell lung cancer (NSCLC) (FGFR1 amplification), breast (FGFR1 and 2 amplification), 
gastric (FGFR2 amplification), bladder (FGFR3 activating mutation or gene translocation), endometrial (FGFR2 
activating mutation), multiple myeloma (FGFR3 gene translocation), and rhabdomyosarcoma 
(FGFR4-activating mutation).
TAS-120 is a novel selective small molecule FGFR inhibitor.
TAS-120 equally inhibited all 4 subtypes of FGFR and showed high selectivity for FGFR when tested against a 
panel of 296 kinases.  Half maximal inhibitory concentration (IC50) values (nmol/L) were 3.9 for FGFR1, 1.3 for 
FGFR2, 1.6 for FGFR3, and 8.3 for FGFR4.  TAS-120 was highly active against cancer cell lines with FGFR 
gene abnormalities including cancer cell lines that acquired resistance to other (adenosine triphosphate 
(ATP)-competitive FGFR tyrosine kinase inhibitors (TKIs).  In vitro studies have shown that TAS-120 
selectively inhibits cell growth of human cancer cell lines that have FGFR gene abnormalities.  In vivo studies 
showed that TAS-120 had strong antitumor efficacy in nude mouse or nude rat xenograft models bearing tumors 
with various FGFR gene abnormalities (FGFR1 or FGFR2 amplification and FGFR3 translocation).  
In addition, TAS-120 retained inhibitory potency against mutant FGFR2 including the V565I gatekeeper 
mutation with a similar potency compared to wild type FGFR2.  N550H and E566G mutations in the FGFR2 
hinge region, which were reported to cause resistance to dovitinib (another FGFR inhibitor), were also sensitive 
to TAS-120.  Furthermore, TAS-120 showed inhibitory potency against mutant FGFR2 including a K660M 
activation loop mutation.  IC50 values for pFGFR2 inhibition (nmol/L) were 0.9 for WT, 1.3 for V565I, 3.6 for 
N550H, 2.3 for E566G, and 5.2 for K660M.  In contrast, when several ATP competitive inhibitors of FGFR 
were tested against these FGFR2 mutants, their inhibitory potencies were reduced compared to their potency 
against the wild type.
Cholangiocarcinoma (CCA), a bile duct cancer, is a rare tumor that arises from the malignant transformation of 
epithelial cells of the bile ducts.  It is typically classified as either intrahepatic (iCCA) or extrahepatic (eCCA).  
Intrahepatic cholangiocarcinoma develops in the smaller bile ducts inside the liver and is the least common form 
of the disease (approximately 10%), whereas eCCA includes cancers in the peri-hilar (also known as Klatskin 
tumor) and distal bile duct area and is most common (approximately 90%).
Although CCA is known to have the histological and molecular features of an adenocarcinoma of epithelial cells 
lining the biliary tract, the actual cell of origin is unknown.  Fibroblast growth factor/fibroblast growth factor 
receptor aberrations are a reported genetic modification in CCA. In iCCA, FGFR2 gene rearrangement including 
fusions has been identified as an early driver of oncogenic events.  These gene rearrangement/fusions are present 
in an estimated 10% to 20% of patients.1, 11, 12 Therefore, inhibiting the FGFR pathway in patients with iCCA is a 
plausible therapeutic strategy for appropriately selected patients with this disease.  
For disease that is localized at diagnosis, surgical resection offers the only chance of cure for patients with CCA.  
Unfortunately, symptoms are not usually apparent until CCA is at an advanced stage, and thus, most patients 
(>65%) have disease which is unresectable at diagnosis.  Unresectable locally advanced (stage III) and 
metastatic (stage IV) disease has a poor prognosis with 5-year overall survival (OS) of 10% and 0%, 
respectively. For such patients, chemotherapy and supportive care are usually offered.13  Although there are no 
approved treatments for CCA, gemcitabine/cisplatin is the standard 1st line chemotherapy regimen for patients 
with advanced, metastatic, unresectable CCA.  There is no standard regimen beyond first line treatment.14 In the 
second line treatment setting,  a retrospective evaluation of 761 patients with advanced biliary tract cancers, 

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including CCA has shown a median overall response rate of 7.7% (95% confidence interval (CI): 5% to 11%) 
and a median progression-free survival (PFS) of 3.2 months (95% CI: 2.7 – 3.7 months).13 These poor results 
confirm a substantial unmet medical need for new therapies in patients with advanced CCA who have failed 
initial chemotherapy.
The FGFR signaling axis has been well characterized for its role in proliferation, differentiation, migration, and 
survival, and it is fundamental to embryonic development, regulation of angiogenesis, and wound healing in 
adults. Dysregulation of the FGFR signaling pathway has been associated with many developmental disorders 
and with cancer. An extensive amount of literature indicates that FGFR is one of the receptor tyrosine kinases 
most frequently mutated or otherwise abnormally activated in late-stage human cancer. 
Therefore, FGFR has been shown to be a valid target, and TAS-120 is a selective inhibitor of FGFR. TAS-120 
exhibits convincing antitumor activity in several xenograft models. Importantly, it delivers antitumor efficacy in 
xenograft models with a large safety window.
This Phase 1/2 clinical trial was planned to investigate the pharmacokinetics (PK), pharmacodynamics, efficacy, 
safety, and tolerability of TAS-120 in patients with advanced solid tumors, with or without FGFR abnormalities 
who have failed all standard therapies or for whom standard therapy does not exist.
During the Phase 1 Dose Escalation part of the study, dose levels of 4, 8, 16, 20 and 24 mg once daily (QD) 
were evaluated.  At 24 mg, 3 of 9 evaluable patients experienced a dose-limiting toxicity (DLT) during Cycle 1, 
thus, 24 mg was determined as the DLT dose level. At 20 mg QD, no DLT was reported in the 5 evaluable 
patients during Cycle 1, and thus, 20 mg QD was determined as the maximum tolerated dose (MTD) and 
recommended Phase 2 dose (RP2D). 
The original design of the Phase 2 portion of the study (enrolling patients with iCCA harboring FGFR2 gene 
fusions) was based on preliminary anti-tumor activity observed in this population in the Phase 1 portions of the 
study.  Specifically, at the time the Phase 2 portion was designed (data cut off 17 September 2017), a total of 3 
confirmed partial responses had been observed among 14 response-evaluable patients with iCCA harboring 
FGFR2 gene fusions.  Accordingly, as of Amendment 7 to this protocol, the study population for the Phase 2 
portion of the study is to include approximately 100 patients with iCCA harboring confirmed FGFR2 gene 
fusions or other FGFR2 rearrangements.  
A formal interim analysis will be performed when approximately 70% all treated patients had 6 months of 
follow-up. Two-sided 95% CI and 99% CI will both be provided for the primary efficacy analysis.  A safety 
analysis will also be performed at this time, and the results will be shared with the SRC.

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Study Objectives:
Phase 1 Dose Escalation
Phase 1 Dose Escalation has been completed as of Amendment 6.
Phase 1 Expansion
Primary
!
To evaluate ORR in cholangiocarcinoma (intra-hepatic [iCCA] or extra-hepatic [eCCA]) patients 
with tumors harboring FGFR2 gene fusions or other FGFR abnormalities.
!
To evaluate ORR and EPR (defined as progression-free rate at the end of Cycle 2) in patients with 
primary CNS tumors harboring FGFR gene fusions or FGFR1 activating mutations (Appendix A).
!
To evaluate ORR in a basket of tumor types with tumors harboring FGFR2 amplifications.
!
To evaluate ORR in a basket of tumor types with tumors harboring any FGFR gene fusions or 
activating mutations Appendix A). 
Secondary 
!
To investigate the safety of TAS-120.
!
To evaluate disease control rate (DCR), DOR, PFS and OS in each treatment group.
Phase 2
Primary
!
To confirm ORR in iCCA patients with FGFR2 gene fusions or other FGFR2 rearrangements based on 
independent central radiology review. 
Key secondary
!
To evaluate DOR
Other secondary
!
To evaluate the safety and tolerability of TAS-120
!
To evaluate DCR, PFS, and OS
!
To evaluate Patient-Reported Outcomes (PROs)
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Study Design:
This is an open-label, nonrandomized, dose-escalation and dose-expansion, Phase 1/2 study of TAS-120, 
evaluating the safety, tolerability, PK, pharmacodynamic, and antitumor activity of TAS-120 in patients with 
advanced solid tumors with FGF/FGFR-related abnormalities who have failed all standard therapies or for whom 
standard therapy does not exist or is not tolerated.
The study will be conducted in 3 parts: 
!
Phase 1 Dose Escalation: to determine the MTD and/or RP2D of TAS-120 
!
Phase 1 Expansion: to further evaluate the efficacy and safety of the MTD and/or RP2D of TAS-120 in 
patients with tumors harboring specific FGF/FGFR aberrations;
!
Phase 2: to confirm the ORR of TAS-120 in iCCA patients with tumors harboring FGFR2 gene fusions
or other FGFR2 rearrangements.
As of Amendment 6, the Phase 1 Dose Escalation Phase is completed and the MTD/RP2D of 20 mg QD was 
established.  Details of the Phase 1 Dose Escalation study design can be found in previous versions of the study 
protocol.
Study Duration:
Patients will receive study drug (TAS-120) according to the proposed treatment schedule until disease 
progression, occurrence of intolerable side effects, removal by the investigator, withdrawal of consent, or other 
criteria for discontinuation are met (Section 7.3, Discontinuation Criteria).
For the Phase 1 Expansion part of the study, patients in each treatment group should be followed for survival for 
up to 12 months after the last patient enrolled in that group. 
For Phase 2, patients should be followed for survival for up to 18 months after the last patient enrolled in this 
phase of the study. 
Study Population:
Phase 1 Dose Escalation
Phase 1 Dose Escalation has been completed as of Amendment 6.  Patients with advanced solid tumors, with or 
without FGFR abnormalities who have failed all standard therapies or for whom standard therapy does not exist.
Phase 1 Expansion and Phase 2
Has histologically or cytologically confirmed, locally advanced, metastatic cancer meeting the following criteria:
a.
Phase 1 Expansion
I.
Patient has failed (or in the case of Group 2, failed or refused) all standard therapies or 
standard therapy does not exist or is not tolerated. 
II.
Patient is eligible for 1 of the following enrollment groups, based on diagnosis, prior therapy, 
and FGF/FGFR aberrations as shown:
a.
Group 1 (enrollment suspended as of Amendment 7): Patient has intrahepatic or 
extrahepatic cholangiocarcinoma harboring FGFR2 gene fusions.
b.
Group 2: Patient has intrahepatic or extrahepatic cholangiocarcinoma harboring 
FGFR2 gene fusions, and has not received or received less than 1 cycle of prior 
chemotherapy (due to intolerance or patient refusal).
c.
Group 3 (enrollment suspended as of Amendment 7): Patient has intrahepatic or 
extrahepatic cholangiocarcinoma harboring FGFR2 gene fusions and has received 
prior treatment with FGFR inhibitors.
d.
Group 4 (enrollment suspended as of Amendment 7): Patient has intrahepatic or 
extrahepatic cholangiocarcinoma harboring FGFR abnormalities other than FGFR2 
gene fusions (for example, mutations, rearrangements, or amplifications).

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e.
Group 5: Patient has a primary CNS tumor harboring FGFR gene fusion or FGFR1 
activating mutation and fulfills the following criteria (i and ii).
i.
Patients who are presenting in recurrence or relapse must have at least one 
measurable enhancing mass lesion with 2 perpendicular diameters of at least 
10 mm documented on baseline contrast magnetic resonance imaging (MRI) 
(gadolinium-based MRI).  
ii.
Patients should be on a stable dose of steroids for at least 7 days prior to 
obtaining the baseline contrast MRI of the brain and at least 7 days prior to 
starting study drug.
f.
Group 6 (enrollment suspended as of Amendment 7): Patient has advanced urothelial 
carcinoma harboring FGFR3 fusions or FGFR3 activating mutations.
g.
Group 7: Patient has any tumor type not included in one of the prior groups, 
harboring FGFR2 amplification (no minimum number of copies).  
h.
Group 8 (enrollment suspended as of Amendment 7): Patient has any tumor type not 
included in one of the prior groups, harboring FGFR gene fusions or activating 
mutations.  
b.
Phase 2
I.
Patient has histologically or cytologically confirmed, locally advanced, metastatic, 
unresectable iCCA harboring FGFR2 gene fusions or other FGFR2 rearrangements based on 
results from either of the following (see Section 9.1 for details): 
a.
Testing by Foundation Medicine:
i.
As part of study pre-screening; or
ii.
Previously tested by Foundation Medicine; in this case, it is requested that 
tumor tissue be provided to Foundation Medicine if available.
b.
Local laboratory testing using next generation sequencing [NGS], fluorescence in situ 
hybridization [FISH], or other assays that can determine FGFR2 gene fusions or other 
FGFR2 rearrangements on tumor tissues or from ctDNA. It is requested that patients 
enrolled on this basis provide tumor tissues to Foundation Medicine, if available from 
either archival samples or fresh tumor biopsy.
II.
Patient has been treated with at least one prior systemic gemcitabine and platinum-based 
chemotherapy.  Patients with prior adjuvant gemcitabine-platinum chemotherapy are eligible if 
the patient had recurrence within 6 months of the last dose of the regimen.
III.
Patient has documentation of radiologic disease progression following the most recent prior 
therapy.
Planned Sample Size:
For the Phase 1 Expansion, approximately 185 patients will be enrolled. For Phase 2, approximately 100 patients 
with iCCA harboring confirmed FGFR2 gene fusions or other FGFR2 rearrangements will be treated.
Dosing and Treatment Schedule Rationale:
The 20 mg QD of TAS-120 has been selected as the dose for the Phase 2 part of the study in iCCA patients as 
well as all Phase 1 Expansion cohorts.

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Treatment Regimen:
TAS-120 will be administered as a daily, continuous, 21-day treatment cycle until at least 1 of the criteria for 
study discontinuation is met (Section 7.3, Discontinuation Criteria). There are no breaks in dosing between 
cycles.  Patients should follow the instructions of the treating physician on study drug administration during 
treatment. Patients are required to fast for at least 2 hours before and 1 hour after administration of TAS-120. 
Patients will be permitted to drink water during this period. Dietary restrictions that limit phosphate intake may 
reduce the risk of hyperphosphatemia (see Section 7.8). On non-PK sampling days, TAS-120 can be 
administered in the morning or evening at the same time (if possible) each day. If a patient misses a dose (i.e., 
did not take TAS-120 for > 12 hours of the scheduled time of that day), the patient should take the dose on the 
next day. 
Safety Criteria for Evaluation:
Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria 
for Adverse Events (CTCAE) (version 4.03) will be used.
Efficacy Criteria for Evaluation:
Please note: for patients who discontinued treatment for reasons other than disease progression, tumor 
assessments should be continued until radiologic disease progression or initiation of new anticancer therapy 
(whichever occurs first).
Solid Tumors
Measurements of solid tumors will be performed throughout study treatment using Response Evaluation Criteria 
in Solid Tumors (RECIST) guidelines (version 1.1, 2009).  Radiographic tumor assessments (computed 
tomography [CT] scan with contrast will be performed at baseline and at the end of every 2 cycles (up to 
+ 2 weeks) up to Cycle 4 (or as clinically indicated).  Following Cycle 4, CT scans will be performed after every 
3 cycles (± 7 days) or as clinically indicated, and at study completion.  
Brain Tumors
Patients with brain tumors will be assessed using Response Assessment in Neuro-Oncology (RANO) criteria 
(2010). Patients with brain tumors will be evaluated for response by contrast magnetic resonance imaging (MRI) 
(gadolinium-based magnetic resonance imaging [Gd-MRI]). All MRIs should be performed when the patient is 
on a stable dose of steroids. Gd-MRI will be performed at baseline and at the end of every 2 cycles (up to 
+ 2 weeks) up to Cycle 4 (or as clinically indicated).  Following Cycle 4, Gd-MRI scans will be performed after 
every 3 cycles (± 7 days) or as clinically indicated, and at study completion.
Neurological examination for patients with brain tumors must always be performed within one week of the date 
of the Gd-MRI as part of the response assessment.
Endpoints
Phase 1 Expansion: the primary endpoint is ORR in each treatment group (and EPR for primary CNS tumors) 
and the secondary endpoints of DOR, DCR, PFS, and OS in each treatment group. 
Phase 2: the primary endpoint is ORR and the secondary endpoints of DOR, DCR, PFS, PROs and OS.
Primary endpoints will be based on the independent review of images by the Core Imaging Laboratory. In 
addition, for the Phase 2 part of the study, sensitivity analyses for some key efficacy endpoints (e.g., ORR, and 
PFS) will be performed based on investigators or local radiologist assessments.  
Statistical Methods:
Analysis Populations
The Safety Population will include all patients who received at least 1 dose of TAS-120. This population will be 
the primary population for safety evaluation. 
The DLT Evaluable Population was defined for Phase 1 Dose Escalation only; Phase 1 Dose Escalation has been 
completed as of Amendment 6.

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The PK and Pharmacodynamic Population will consist of all patients who received TAS-120 and have TAS-120 
evaluable plasma and/or urine data. All such patients will be evaluated for PK and pharmacodynamics unless 
significant protocol deviations have impacted the data or key dosing information is missing. Changes to the 
procedures, which may impact the quality of PK and pharmacodynamic data, will be considered “PK and 
pharmacodynamics relevant protocol deviations.” Examples include sample processing errors that lead to 
inaccurate bioanalytical results and/or inaccurate dosing on the day of PK and pharmacodynamic sampling.
The Efficacy Population is defined for each portion of the study as follows:
!
Phase 1 Dose Escalation:  All treated patients (safety population) 
!
Phase 1 Expansion: All treated patients (safety population)
!
Phase 2: All treated iCCA patients with confirmed FGFR2 gene fusions or other FGFR2 
rearrangements
Efficacy Analyses
For Phase 1 Expansion, efficacy data for the primary endpoint of ORR (and EPR for primary CNS tumors), and 
secondary endpoints of PFS, DCR, DOR, and OS will be summarized for each treatment group. 
For Phase 2, efficacy data for the primary endpoint of ORR and secondary endpoints of DOR, PFS, DCR, 
Patient-Reported Outcomes (PROs) and OS will be summarized.  For PROs, the analysis of a EuroQol-5D 
measure of health-related quality of life (EQ-5D) and the European Organization for Research and Treatment of 
Cancer Quality of Life Questionnaire (EORTC QLQ-C30) will be performed in all treated patients who have an 
assessment at baseline and at least one subsequent assessment.
Determination of Sample Size: 
Phase 1 Dose Escalation: 
There were 86 patients enrolled in the Phase 1 Dose Escalation part of the study which has been completed as of 
Amendment 6.
Phase 1 Expansion:
Up to approximately 185 patients will be enrolled as outlined below:
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Phase 2:
Approximately 100 iCCA patients with FGFR2 gene fusions or other FGFR2 rearrangements will be treated. 
Interim Analyses:
Interim reviews of safety will be performed approximately every 3 months throughout the study, until the 
interim analysis cut-off. These interim reviews will be performed by a Safety Review Committee (SRC), 
comprising, at minimum:
!
1 independent investigator and 1 independent statistician, neither of whom is directly involved in the 
conduct or analysis of the study; and
!
A total of 5-6 study investigators representing each region in which patients are enrolled.
A complete description of the composition of the SRC and details on the interim analysis process will be 
provided in a separate safety review charter.
In addition to these reviews, the Sponsor will share safety data from the trial with all primary investigators 
throughout the conduct of the study.
A formal interim analysis will be performed when approximately 70% all treated patients had 6 months of 
follow-up. Two-sided 95% CI and 99% CI will both be provided for the primary efficacy analysis.  A safety 
analysis will also be performed at this time, and the results will be shared with the SRC.
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3.
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES
TABLE OF CONTENTS
SUMMARY OF CHANGES...........................................................................................................2
1.
SYNOPSIS ...................................................................................................................4
2.
STUDY SCHEDULES...............................................................................................12
3.
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES...............20
4.
LIST OF ABBREVIATIONS AND TERMS.............................................................28
5.
INTRODUCTION AND STUDY RATIONALE ......................................................31
5.1.
Unmet Medical Need in Treatment of Cholangiocarcinoma......................................31
5.2.
TAS-120 .....................................................................................................................32
5.2.1.
Preclinical Experience with TAS-120 ........................................................................32
5.2.2.
Clinical Experience with TAS-120.............................................................................32
5.3.
Study Rationale...........................................................................................................33
5.4.
Rationale for Selection of RP2D of TAS-120............................................................33
5.5.
Rationale for the Phase 1 Expansion Part of the Study ..............................................33
5.6.
Rationale for Phase 2 Part of the Study......................................................................34
6.
STUDY OBJECTIVES ..............................................................................................35
6.1.
Phase 1 Dose Escalation.............................................................................................35
6.2.
Phase 1 Expansion......................................................................................................35
6.3.
Phase 2........................................................................................................................36
7.
INVESTIGATIONAL PLAN.....................................................................................37
7.1.
Study Design...............................................................................................................37
7.1.1.
Phase 1 Expansion......................................................................................................38
7.1.2.
Phase 2........................................................................................................................39
7.1.3.
Study Duration............................................................................................................40
7.2.
Study Population.........................................................................................................40
7.2.1.
Inclusion Criteria ........................................................................................................40
7.2.2.
Exclusion Criteria.......................................................................................................42
7.3.
Discontinuation Criteria..............................................................................................44
7.3.1.
End of Treatment Discontinuation Criteria ................................................................44
7.4.
Patient Numbering and Treatment Allocation............................................................44

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7.5.
Replacement Criteria ..................................................................................................45
7.6.
Prohibited Medications and Therapies .......................................................................45
7.7.
Concomitant Medications and Therapies ...................................................................45
7.7.1.
Effective Contraception During Study .......................................................................47
7.8.
Dietary Restrictions ....................................................................................................48
8.
STUDY DRUG...........................................................................................................49
8.1.
Study Drug Administration and Dose Modification Procedures................................49
8.1.1.
Study Drug Administration.........................................................................................49
8.1.2.
Treatment Regimen ....................................................................................................49
8.1.3.
Dose Reduction/Modification Procedures..................................................................49
8.1.3.1.
TAS-120 Dose Reductions for Treatment-emergent Toxicities.................................49
8.2.
Description and Labeling............................................................................................53
8.2.1.
TAS-120 .....................................................................................................................53
8.2.2.
Packaging and Labeling..............................................................................................54
8.2.3.
Storage ........................................................................................................................54
8.2.4.
Patient Instructions for Handling Study Drug ............................................................54
8.3.
Drug Accountability ...................................................................................................54
8.4.
Blinding ......................................................................................................................55
9.
STUDY PROCEDURES............................................................................................56
9.1.
Pre-screening of Tumor Tissue Sample for FGFR2 Gene Fusions or other 
FGFR2 Rearrangements in Patients with iCCA (Phase 2 Only)................................56
9.2.
Informed Consent .......................................................................................................57
9.3.
Medical History ..........................................................................................................57
9.4.
Physical Examination .................................................................................................57
9.5.
Height, Vital Signs, and Weight.................................................................................57
9.6.
Performance Status .....................................................................................................57
9.7.
Electrocardiogram.......................................................................................................58
9.8.
Ophthalmological Examination..................................................................................58
9.9.
Neurological Examination..........................................................................................59
9.9.1.
Neurological Examination as part of RANO Evaluation for Patients with 
Primary CNS Tumors .................................................................................................59
9.10.
Clinical Laboratory Evaluations.................................................................................60
9.10.1.
Hematology and Coagulation .....................................................................................60

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9.10.2.
Chemistry....................................................................................................................61
9.10.3.
Urinalysis....................................................................................................................62
9.12.
Pregnancy Test............................................................................................................62
9.13.
Pharmacokinetic Sample Collection...........................................................................63
9.13.1.
Optional Pharmacokinetic Sample Collection for Phase 1 Expansion.......................63
9.13.2.
Pharmacokinetic Blood Sample Collection for Phase 1 Expansion/Phase 2..............63
9.14.
ctDNA Analysis of FGF/FGFR Aberrations ..............................................................64
9.14.1.
ctDNA from Blood Sample for the Analysis of FGF/FGFR Aberrations..................64
9.15.
Prior and Concomitant Medications and Therapies....................................................64
9.16.
Adverse Event Assessment.........................................................................................64
9.17.
Tumor Assessments/Scans..........................................................................................65
9.17.1.
Tumor Assessment for Advanced Solid Tumors........................................................65
9.17.2.
Tumor Assessment for Brain Tumors.........................................................................66
9.18.
Patient-Reported Outcomes........................................................................................66
9.19.
End-of-treatment Visit................................................................................................67
9.20.
30-Day Safety Follow-up ...........................................................................................67
9.21.
Survival Status Follow-up ..........................................................................................67
9.22.
Tumor Tissue Sample Collection (Phase 1 Expansion) .............................................67
10.
EFFICACY ASSESSMENT CRITERIA...................................................................68
10.1.
Efficacy Assessment for Solid Tumors ......................................................................68
10.1.1.
Method of Imaging .....................................................................................................68
10.1.2.
Tumor Definitions ......................................................................................................69
10.1.3.
Response Criteria........................................................................................................70
10.1.3.1.
Target and Non-Target Response Assessments..........................................................71
10.1.3.2.
Objective Response Assessment.................................................................................72
10.1.4.
Best Objective Response Assessment for Solid Tumors............................................73
10.2.
Efficacy Assessment for Brain Tumors......................................................................73
10.2.1.
Method of Imaging .....................................................................................................73
10.2.2.
Tumor Definitions ......................................................................................................73
10.2.2.1.
Measurable and Non-measurable Contrast Enhancing Lesions .................................73
10.2.2.2.
Non-enhancing Lesions ..............................................................................................74
10.2.3.
Response Definitions..................................................................................................74
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11.
REPORTING SAFETY INFORMATION.................................................................77
11.1.
Adverse Events/Serious Adverse Events....................................................................77
11.1.1.
Adverse Events ...........................................................................................................77
11.1.2.
Serious Adverse Events..............................................................................................78
11.1.3.
Reporting of Deaths....................................................................................................79
11.1.4.
Disease Progression....................................................................................................79
11.1.5.
Pregnancy ...................................................................................................................80
11.1.6.
Overdose.....................................................................................................................80
11.1.7.
Medication Errors .......................................................................................................80
11.1.8.
Breaking the Study Blind............................................................................................81
11.2.
Laboratory Evaluations...............................................................................................81
11.2.1.
Reporting and Evaluation of Laboratory Test Results ...............................................81
11.2.2.
Repeat Testing ............................................................................................................81
11.3.
Physical Examination and Performance Status ..........................................................81
11.4.
Vital Signs and Body Weight .....................................................................................81
12.
STATISTICS ..............................................................................................................82
12.1.
Study Populations .......................................................................................................82
12.2.
Statistical Analysis......................................................................................................82
12.2.1.
Patient Disposition, Baseline and Treatment Characteristics.....................................82
12.2.1.1.
Patient Disposition......................................................................................................82
12.2.1.2.
Patient Baseline Characteristics..................................................................................83
12.2.1.3.
Study Treatment..........................................................................................................83
12.2.2.
Efficacy Analysis........................................................................................................83
12.2.2.1.
Objective Response Rate ............................................................................................83
12.2.2.2.
Disease Control Rate ..................................................................................................83
12.2.2.3.
Duration of Response .................................................................................................84
12.2.2.4.
Progression-free Survival ...........................................................................................84
12.2.2.5.
Overall Survival..........................................................................................................84
12.2.2.6.
Patient-Reported Outcomes........................................................................................84
12.2.3.
Safety..........................................................................................................................85
12.2.4.
Pharmacokinetic Analysis ..........................................................................................85
12.2.5.
Pharmacodynamic Analysis (Phase 1 Dose Escalation only).....................................86
12.3.
Determination of Sample Size....................................................................................86

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12.3.3.
Phase 2........................................................................................................................89
12.4.
Interim Analyses.........................................................................................................89
13.
ETHICS ......................................................................................................................90
13.1.
Ethical Considerations................................................................................................90
13.2.
Informed Consent and Patient Information ................................................................90
13.3.
Institutional Review Board/Independent Ethics Committee Approval ......................90
13.4.
Post-study Provisions..................................................................................................91
14.
ADMINISTRATIVE CONSIDERATIONS ..............................................................92
14.1.
Protocol Amendments ................................................................................................92
14.2.
Curriculum Vitae ........................................................................................................92
14.3.
Administrative Structure.............................................................................................92
14.4.
Monitoring Procedures ...............................................................................................92
14.4.1.
Investigator’s Responsibilities....................................................................................92
14.4.2.
Sponsor’s Responsibilities..........................................................................................92
14.4.3.
Source Documents......................................................................................................93
14.4.4.
Case Report Form.......................................................................................................93
14.4.5.
Sponsor’s Audits and Regulatory Inspections............................................................93
14.5.
Archiving of Records..................................................................................................94
14.6.
Final Report ................................................................................................................94
14.7.
Use and Publication of Study Results.........................................................................94
14.8.
Financial Disclosure ...................................................................................................95
14.9.
Termination of the Study............................................................................................95
15.
CONFIDENTIALITY AND DATA PROTECTION.................................................96
16.
SIGNATURES OF SPONSOR AND INVESTIGATOR ..........................................97
17.
REFERENCES ...........................................................................................................98
APPENDIX A.
LIST OF FGFR MUTATIONS.......................................................................100
APPENDIX B.
FGFR3 MUTATIONS.....................................................................................102
APPENDIX C.
ECOG PERFORMANCE STATUS................................................................103
APPENDIX D.
NEW YORK HEART ASSOCIATION (NYHA) CLASSIFICATION.........104
APPENDIX E.
DIETARY GUIDELINES FOR TREATMENT OF 
HYPERPHOSPHATEMIA ......................................................................................105
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APPENDIX F.
CLASSIFICATION OF SUBSTRATES, INHIBITORS, AND 
INDUCERS OF CYP ENZYMES AND TRANSPORTERS ..................................106
APPENDIX G.
SUPPLEMENTAL REQUIREMENTS FOR JAPAN ONLY........................109
APPENDIX H.
SUMMARY OF PROTOCOL AMENDMENTS...........................................111

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LIST OF TABLES
Table 1:
Study Schedule for Phase 1 Expansion ......................................................................12
Table 2:
Study Schedule for Phase 2 ........................................................................................16
Table 3:
Abbreviations and Terms............................................................................................28
Table 4:
List of TAS-120 Clinical Trials..................................................................................33
Table 5:
TAS-120 Dose Reduction Levels ...............................................................................49
Table 6:
TAS-120 Dosing Modification for Nonhematologic Toxicities.................................50
Table 7:
Recommendations for Hyperphosphatemia Management..........................................51
Table 8:
TAS-120 Dose Interruption and Modification Criteria for Hematologic 
Toxicities ....................................................................................................................52
Table 9:
Required Follow-up for Toxicities .............................................................................53
Table 10:
TAS-120 Product description and packaging information.........................................54
Table 11:
Laboratory Assessments for TAS-120-101 ................................................................61
Table 12:
Pharmacokinetic Blood Sample Collection for Phase 1 Expansion/Phase 2..............64
Table 13:
Time Point Response for Patients with Target (+/- Non-Target) Disease..................72
Table 14:
Time Point Response for Patients with Only Non-Target Disease.............................73
Table 15:
Summary of RANO Response Criteria.......................................................................76
Table 16:
Multinomial Two-stage Design Boundaries for Group 5 (Based on Objective 
Response and Early Progression) ...............................................................................87
Table 17:
Summary of Group 7 Design......................................................................................88
Table 18:
Observed ORR with Exact 95% Confidence Interval ................................................89

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LIST OF FIGURES
Figure 1:
Overall Study Schema ................................................................................................37
Figure 2:
Group 7 Tumor Types ................................................................................................38
Figure 3:
Study Schema for Phase 2 ..........................................................................................39
Figure 4:
Algorithm for Selection of Target Lesions:  RANO Criteria .....................................74

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4.
LIST OF ABBREVIATIONS AND TERMS
Table 3:
Abbreviations and Terms
Abbreviation or Term
Explanation
AE
Adverse event
Ae%
Urinary excretion rate as % of dose (QOD arm)
ALT
Alanine aminotransferase
ANC
Absolute neutrophil count
APTT
Activated partial thromboplastin time
ASCO
American Society of Clinical Oncology
AST
Aspartate aminotransferase
ATP
Adenosine triphosphate
AUC
Area under the concentration time curve
β-HCG
Beta-human chorionic gonadotropin
BID
Twice a day
BUN
Blood urea nitrogen
CCA
Cholangiocarcinoma
Ccr
Calculated creatinine clearance 
CFR
Code of Federal Regulations
CI
Confidence interval
CK
Creatinine kinase
CL/F
Oral clearance
CLr
Renal clearance
Cmax
Maximum observed plasma concentration
CR
Complete response
CRA
Clinical Research Associate
CRO
Contract Research Organization
CSF
Cerebrospinal fluid
CT
Computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
ctDNA
Circulating tumor DNA
CYP
Cytochrome P450
DCR
Disease control rate
DLT
Dose-limiting toxicity
DOR
Duration of response
eCCA
Extra-hepatic cholangiocarcinoma
ECG
Electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
Electronic case report form
EDC
Electronic data capture

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Abbreviation or Term
Explanation
EORTC QLQ-C30
European Organization for Research and Treatment of 
Cancer Quality of Life Questionnaire
EOT
End-of-treatment
EP
Early progression
EPR
Early progression rate
EQ-5D
EuroQol-5D measure of health-related quality of life
EU
European Union
FFPE 
Formalin fixed paraffin embedded
FGF
Fibroblast growth factor
FGFR
Fibroblast growth factor receptor
FISH
Fluorescence in situ hybridization
GBM
Glioblastoma multiforme 
G-CSF
Granulocyte colony-stimulating factor
GCP
Good Clinical Practice
Gd-MRI  
Gadolinium-based magnetic resonance imaging
GnRH
Gonadotropin-releasing hormone
Hgb
Hemoglobin
IB
Investigator’s Brochure
iCCA
Intra-hepatic cholangiocarcinoma
IC50 
50% inhibitory concentration
ICF
Informed consent form
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
IND
Investigational New Drug
INR
International normalized ratio
IRB
Institutional Review Board
IU
International Units
IXRS
Interactive voice/web response system
LH-RH
Luteinizing hormone-releasing hormone
LLN
Lower limit of normal
MedDRA
Medical Dictionary for Regulatory Activities
MRI
Magnetic resonance imaging
MRT
Mean residence time
ms
Milliseconds
MTD
Maximum tolerated dose
NCI
National Cancer Institute
NGS
Next generation sequencing
NSCLC
Non-small cell lung cancer
NYHA
New York Heart Association

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Abbreviation or Term
Explanation
ORR
Objective response rate
OS
Overall survival
P
Phosphorus
PD
Progressive disease
PFS
Progression-free survival
P-gp
P-glycoprotein 
PK
Pharmacokinetic(s)
PLT
Platelets
PMDA
Pharmaceuticals and Medical Devices Agency
PR
Partial response
PROs
Patient-Reported Outcomes
PT
Preferred term
QD
Once daily (continuous) dosing
QOD
3-times-a-week (Monday, Wednesday, and Friday) dosing
QoL
Quality of life
QTcF
Fridericia’s corrected QT interval 
R
Response
RANO
Response Assessment in Neuro-Oncology
RBC
Red blood cell
RECIST
Response Evaluation Criteria in Solid Tumors
RP2D
Recommended Phase 2 dose
SAE
Serious adverse event
SAP
Statistical Analysis Plan
SD
Stable disease
SIRT
Selective internal radiotherapy 
SOC
System Organ Class
SOP
Standard operating procedure
TACE
Transarterial chemoembolization  
t1/2
Elimination half-life 
TID
Three times a day
Tmax
Time to maximum plasma concentration
TOI
Taiho Oncology, Incorporated
ULN
Upper limit of normal
USA
United States of America
Vd/F
Volume of distribution
WBC
White blood cell
WHO
World Health Organization
WOCBP
Women of child-bearing potential

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5.
INTRODUCTION AND STUDY RATIONALE
The progression of cancers is caused by a complex series of multiple genetic and molecular
events including gene mutations and chromosomal translocations.1
The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling axis plays 
an important role in normal organ, vascular, and skeletal development. On the other hand, 
activating FGFR gene abnormalities are reported in various tumor types, and FGFR 
abnormalities are considered a driving event for tumor formation.2, 3, 4 Genetic modifications or 
overexpression of FGFRs have been associated with tumorigenesis and progression in breast, 
lung, gastric, hematologic malignancies, and others. 4, 5, 6, 7, 8, 9 Activating FGFR gene 
abnormalities are reported in various cancers including non-small cell lung cancer (NSCLC) 
(FGFR1 amplification), breast (FGFR1 and 2 amplification), gastric (FGFR2 amplification), 
bladder (FGFR3 activating mutation or gene translocation), endometrial (FGFR2 activating 
mutation), multiple myeloma (FGFR3 gene translocation), and rhabdomyosarcoma (FGFR4 
activating mutation). 
Of note, according to published results, 22% of patients with squamous cell lung cancer have an 
FGFR1 amplification, 10% of patients with breast cancer have FGFR1 and 2 amplifications, 
10% of patients with gastric cancer have an FGFR2 amplification, more than 50% of patients 
with nonmuscle invasive bladder cancer have an FGFR3-activating mutation or gene 
translocation, 12% of patients with endometrial cancer have an FGFR2-activating mutation, 5% 
of patients with multiple myeloma have an FGFR3 gene-involving translocation, 7.5% of 
patients with rhabdomyosarcoma have an FGFR4-activating mutation, and 3% of patients with 
small-cell lung cancer have an FGFR1 amplification. 3, 10, 11, 12 . In all the tumor types described 
above for which FGFR abnormalities have been described, nonresectable advanced or metastatic 
disease remains incurable and ultimately resistant to currently available chemotherapies.
5.1.
Unmet Medical Need in Treatment of Cholangiocarcinoma
Cholangiocarcinoma (CCA), a bile duct cancer, is a rare tumor that arises from the malignant 
transformation of epithelial cells of the bile ducts.  It is typically classified as either intrahepatic 
(iCCA) or extrahepatic (eCCA).  Intrahepatic cholangiocarcinoma develops in the smaller bile 
ducts inside the liver and is the least common form of the disease (approximately 10%), whereas 
eCCA includes cancers in the peri-hilar (also known as Klatskin tumor) and distal bile duct area 
and is most common (approximately 90%).
Although CCA is known to have the histological and molecular features of an adenocarcinoma 
of epithelial cells lining the biliary tract, the actual cell of origin is unknown.  Fibroblast growth 
factor/fibroblast growth factor receptor aberrations are a reported genetic modification in CCA.
In iCCA, FGFR2 gene rearrangement, including fusions, has been identified as an early driver of 
oncogenic events.  These gene rearrangements/fusions are present in an estimated 10% to 20% of 
patients.1, 11, 12 Therefore, inhibiting the FGFR pathway in patients with iCCA is a plausible 
therapeutic strategy for appropriately selected patients with this disease.  
For disease which is localized at diagnosis, surgical resection offers the only chance of cure.  
Unfortunately, symptoms are not usually apparent until CCA is at an advanced stage, and thus, 
most patients (>65%) have disease which is unresectable at diagnosis.  Unresectable, locally 
advanced (stage III) and metastatic (stage IV) disease has a poor prognosis with 5-year overall 

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survival (OS) of 10% and 0%, respectively. For such patients, chemotherapy and supportive care 
are usually offered.13 Although there are no approved treatments for CCA, gemcitabine/cisplatin 
is the standard 1st line chemotherapy regimen for patients with advanced, metastatic, 
unresectable CCA.  There is no standard regimen beyond first line.14  In the second line 
treatment setting of chemotherapy, a retrospective evaluation of 761 patients with advanced 
biliary tract cancers, including CCA has shown a median overall response rate of 7.7% (95% 
confidence interval (CI): 5% to 11%) and a median progression-free survival (PFS) of 3.2 
months (95% CI: 2.7 – 3.7 months).13 These poor results confirm a substantial unmet medical 
need for new therapies in patients with advanced CCA who have failed initial chemotherapy.
5.2.
TAS-120
TAS-120 is a novel selective and irreversible small molecule FGFR inhibitor.
5.2.1.
Preclinical Experience with TAS-120
TAS-120 equally inhibited all 4 subtypes of FGFR and showed high selectivity for FGFR when 
tested against a panel of 296 kinases.  Half maximal inhibitory concentration (IC50) values 
(nmol/L) were 3.9 for FGFR1, 1.3 for FGFR2, 1.6 for FGFR3, and 8.3 for FGFR4.  TAS-120 
was highly active against cancer cell lines with FGFR gene abnormalities including cancer cell 
lines that acquired resistance to other ATP-competitive FGFR tyrosine kinase inhibitors (TKIs).  
In vitro studies have shown that TAS-120 selectively inhibits cell growth of human cancer cell 
lines that have FGFR gene abnormalities.  In vivo studies showed that TAS-120 had strong 
antitumor efficacy in nude mouse or nude rat xenograft models bearing tumors with various 
FGFR gene abnormalities (FGFR1 or 2 amplification and FGFR3 translocation).  
In addition, TAS-120 retained inhibitory potency against mutant FGFR2 including the V565I 
gatekeeper mutation with a similar potency compared to wild type FGFR2.  N550H and E566G 
mutations in the FGFR2 hinge region, which were reported to cause resistance to dovitinib 
(another FGFR inhibitor), were also sensitive to TAS-120.  Furthermore, TAS-120 showed 
inhibitory potency against mutant FGFR2 including a K660M activation loop mutation.  IC50
values for pFGFR2 inhibition (nmol/L) were 0.9 for WT, 1.3 for V565I, 3.6 for N550H, 2.3 for 
E566G, and 5.2 for K660M.  In contrast, when several competitive inhibitors of FGFR were 
tested against these FGFR2 mutants, their inhibitory potencies were reduced compared to their 
potency against the wild type. See the current TAS-120 Investigator’s Brochure (IB) for 
additional information. 
5.2.2.
Clinical Experience with TAS-120
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Table 4:
List of TAS-120 Clinical Trials 
Study Number 
Number of 
Patients 
Enrolleda
Number of 
Patients 
Ongoinga
Dose and schedule: number 
of patients enrolleda
QD = once daily; QOD = every other day
a
As of 20 September 2017
5.3.
Study Rationale
The FGF/FGFR signaling axis has been well characterized for its role in proliferation,
differentiation, migration, and survival, and it is fundamental to embryonic development, 
regulation of angiogenesis, and wound healing in adults. Dysregulation of the FGFR signaling 
pathway has been associated with many developmental disorders and with cancer. An extensive 
amount of literature indicates that FGF/FGFR is one of the receptor tyrosine kinases most 
frequently mutated or otherwise abnormally activated in late-stage human cancer. 
Therefore, FGFR has been shown to be a valid target, and TAS-120 is a selective inhibitor of 
FGFR. TAS-120 exhibits convincing antitumor activity in several xenograft models. 
Importantly, it delivers antitumor efficacy in xenograft models with a large safety window.
This Phase 1/2 clinical trial was planned to investigate the PK, pharmacodynamics, efficacy, 
safety, and tolerability of TAS-120 in patients with advanced solid tumors, with FGF/FGFR 
abnormalities who have failed all standard therapies or for whom standard therapy does not exist.
5.4.
Rationale for Selection of RP2D of TAS-120 
During the Phase 1 Dose Escalation part of the study, dose levels of 4, 8, 16, 20 and 24 mg QD 
were evaluated.  At 24 mg, 3 of 9 evaluable patients experienced a dose-limiting toxicity (DLT) 
during Cycle 1, thus, 24 mg was determined as the DLT dose level. At 20 mg QD, no DLT was 
reported in the 5 evaluable patients during Cycle 1, and thus, 20 mg QD was determined as the 
maximum tolerated dose (MTD) and RP2D. 
5.5.
Rationale for the Phase 1 Expansion Part of the Study
The Phase 1 Expansion part of the study included a total of 8 treatment groups enrolling different 
patient populations; 3 of these groups remain open as of Amendment 7 to this protocol.  This 
includes a group of patients with cholangiocarcinoma (CCA), a group of patients with primary 
CNS tumors harboring FGFR gene fusion or FGFR1 activating mutation, and 1 basket cohort 
including patients with solid tumors that harboring FGFR2 amplifications. 
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Expansion in patients with CCA is based upon clinical evidence of preliminary anti-tumor 
activity in this condition observed during the Phase I Dose Escalation portion of the study 
(please see Section 5.6 for additional detail).
The group of patients with primary CNS tumors is included on the basis of nonclinical studies 
demonstrating the viability of FGFR1 activating mutations and FGFR gene fusions as therapeutic 
targets in human gliomas.20,21
Group 7 (basket of tumor types harboring FGFR2 amplifications) was designed based on 
research suggesting that response to treatment targeting the FGFR may be increased across a 
wide range of different solid tumors harboring this form of mutation.22  As FGFR2 
amplifications are most common in ovarian and upper gastrointestinal tumors, these 2 cancer 
types will be included in distinct subgroups of Group 7, with a third subgroup encompassing all 
other tumors with FGFR2 amplifications.
5.6.
Rationale for Phase 2 Part of the Study
The original design of the Phase 2 portion of the study (enrolling patients with iCCA harboring 
FGFR2 gene fusions) was based on preliminary anti-tumor activity observed in this population in 
the Phase 1 portions of the study.  Specifically, at the time the Phase 2 portion was designed 
(data cut off 17 September 2017), a total of 3 confirmed partial responses had been observed 
among 14 response-evaluable patients with iCCA harboring FGFR2 gene fusions.  Accordingly, 
as of Amendment 7 to this protocol, the study population for the Phase 2 portion of the study is
to include approximately 100 patients with iCCA harboring confirmed FGFR2 gene fusions or 
other FGFR2 rearrangements.  

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6.
STUDY OBJECTIVES
6.1.
Phase 1 Dose Escalation
Phase 1 Dose Escalation has been completed as of Amendment 6.
6.2.
Phase 1 Expansion 
Primary
!
To evaluate ORR in cholangiocarcinoma (intra-hepatic [iCCA] or extra-hepatic 
[eCCA]) patients with tumors harboring FGFR2 gene fusions or other FGFR 
abnormalities.
!
To evaluate ORR and EPR (defined as progression-free rate at the end of Cycle 2) in 
patients with primary CNS tumors harboring FGFR gene fusions or FGFR1 activating 
mutations (Appendix A).
!
To evaluate ORR in a basket of tumor types with tumors harboring FGFR2 
amplifications. 
!
To evaluate ORR in a basket of tumor types with tumors harboring any FGFR gene 
fusions or activating mutations Appendix A). 
Secondary
!
To investigate the safety of TAS-120.
!
To evaluate DCR, DOR, PFS, and OS in each treatment group.
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6.3.
Phase 2
Primary
!
To confirm ORR in iCCA patients with FGFR2 gene fusions or other FGFR2 
rearrangements based on independent central radiology review. 
Key secondary
!
To evaluate DOR
Other secondary
!
To evaluate the safety and tolerability of TAS-120.
!
To evaluate DCR, PFS, and OS
!
To evaluate Patient-Reported Outcomes (PROs)
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7.1.3.
Study Duration
Safety monitoring will begin from the time the main study informed consent form (ICF) is 
signed and will continue for 30 days after the last dose of TAS-120 or until the initiation of 
another anticancer therapy, whichever occurs first.
Patients will receive study treatment until disease progression, occurrence of intolerable side 
effects, discontinued from treatment by the investigator, withdrawal of consent, or other criteria 
for discontinuation is met (see Section 7.3, Discontinuation Criteria). A patient is considered 
discontinued from study treatment when TAS-120 is discontinued.
For the Phase 1 Expansion part of the study, patients in each treatment group should be followed 
for survival for up to 12 months after the last patient enrolled in that group.  
For Phase 2, patients should be followed for survival for up to 18 months after the last patient 
enrolled in this phase of the study.
7.2.
Study Population
The study population will include male and female patients with advanced solid tumors or 
primary CNS tumors, according to the following inclusion and exclusion criteria.
7.2.1.
Inclusion Criteria
A patient must meet all of the following inclusion criteria to be eligible for enrollment in this 
study:
1. Provide written informed consent.
2. Is ∀18 years (or according the country's regulatory definition for legal adult age).
3. Has histologically or cytologically confirmed, locally advanced, metastatic cancer 
meeting the following criteria:
a.
Phase 1 Expansion
i.
Patient has failed (or in the case of Group 2, failed or refused) all standard 
therapies or standard therapy does not exist or is not tolerated. 
ii.
Patient is eligible for 1 of the following enrollment groups, based on diagnosis, 
prior therapy, and FGF/FGFR aberrations as shown:
a.
Group 1 (Enrollment Suspended as of Amendment 7): Patient has 
intrahepatic or extrahepatic cholangiocarcinoma harboring FGFR2 gene 
fusions.
b. Group 2: Patient has intrahepatic or extrahepatic cholangiocarcinoma 
harboring FGFR2 gene fusions, and has not received or received less than 
1 cycle of prior chemotherapy (due to intolerance or patient refusal).
c.
Group 3 (Enrollment Suspended as of Amendment 7): Patient has 
intrahepatic or extrahepatic cholangiocarcinoma harboring FGFR2 gene 
fusions and has received prior treatment with FGFR inhibitors.

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d. Group 4 (Enrollment suspended as of Amendment 7): Patient has 
intrahepatic or extrahepatic cholangiocarcinoma harboring FGFR 
abnormalities other than FGFR2 gene fusions (for example, mutations, 
rearrangements, or amplifications).
e.
Group 5: Patient has a primary CNS tumor harboring FGFR gene fusion 
or FGFR1 activating mutation and fulfills the following criteria (i and ii):
i. Patients who are presenting in recurrence or relapse must have at 
least one measurable enhancing mass lesion with 2 perpendicular 
diameters of at least 10 mm documented on baseline contrast 
magnetic resonance imaging (MRI) (gadolinium-based MRI).  
ii. Patients should be on a stable dose of steroids for at least 7 days 
prior to obtaining the baseline contrast MRI of the brain and at 
least 7 days prior to starting study drug.
f.
Group 6 (Enrollment Suspended as of Amendment 7): Patient has 
advanced urothelial carcinoma harboring FGFR3 fusions or FGFR3 
activating mutations.
g. Group 7: Patient has any tumor type not included in one of the prior 
groups, harboring FGFR2 amplification (no minimum number of copies).  
h. Group 8 (Enrollment Suspended as of Amendment 7): Patient has any 
tumor type not included in one of the prior groups, harboring FGFR gene 
fusions or activating mutations.  
b. Phase 2
i.
Patient has histologically or cytologically confirmed, locally advanced, 
metastatic, unresectable iCCA harboring FGFR2 gene fusions or other FGFR2 
rearrangements based on results from either of the following (see Section 9.1 for 
details): 
a.
Testing by Foundation Medicine:
i. As part of study pre-screening; or
ii. Previously tested by Foundation Medicine; in this case, it is 
requested that tumor tissue be provided to Foundation Medicine if 
available.
b. Local laboratory testing using next generation sequencing [NGS], 
fluorescence in situ hybridization [FISH], or other assays that can 
determine FGFR2 gene fusions or other FGFR2 rearrangements on tumor 
tissues or from ctDNA. It is requested that patients enrolled on this basis 
provide tumor tissues to Foundation Medicine, if available from either 
archival samples or fresh tumor biopsy.
ii.
Patient has been treated with at least one prior systemic gemcitabine and 
platinum-based chemotherapy.  Patients with prior adjuvant gemcitabine-platinum 
chemotherapy are eligible if the patient had recurrence within 6 months of the last 
dose of the regimen.

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iii.
Patient has documentation of radiographic disease progression on the most recent 
prior therapy
4. Patient has measurable disease as defined by Response Evaluation Criteria in Solid 
Tumors (RECIST) guidelines (version 1.1, 2009) for advanced solid tumors or RANO 
criteria (2010) for brain tumors.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 on Day 1 of 
Cycle 1 (see Appendix C, ECOG Performance Status).
6. Able to take medications orally (e.g., no feeding tube).
7. Adequate organ function as defined by the following criteria:
a.
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 
×upper limit of normal (ULN); if liver function abnormalities are due to 
underlying liver metastasis, AST and ALT ≤5 × ULN.
b. Total bilirubin ≤ 1.5 × ULN, or ≤3.0 mg/dL for patients with Gilbert’s syndrome.
c.
International normalized ratio (INR) <1.3 (or < 3.0 on anticoagulants)
d. Absolute neutrophil count ≥ 1000/mm3 (i.e., ≥ 1.0 × 109/L by International Units 
[IU]) 
e.
Platelet count ≥ 75,000/mm3 (IU: ≥ 75 × 109/L) 
f.
Hemoglobin ≥ 9.0 g/dL
g. Phosphorus ≤ ULN. 
8. Creatinine clearance (calculated* or measured value**): ≥ 40 mL/min
* For a calculated creatinine clearance (Ccr) value, the eligibility should be determined 
using the Cockcroft-Gault formula:
a.
Male Ccr (mL/min) = Body weight (kg) × (140 – age)/[72 × creatinine (mg/dL)]
b. Female Ccr (mL/min) = male Ccr × 0.85
**A measured Ccr value (i.e., not calculated) should meet this criterion.
9. Women of child-bearing potential (WOCBP) must have a negative pregnancy test (urine 
or serum) within 7 days prior to administration of the first dose of TAS-120. Female 
patients are not considered to be of child-bearing potential if they have a history of 
hysterectomy or are post-menopausal defined as no menses for 12 months without an 
alternative medical cause. Both males and females of reproductive potential must agree to 
use effective birth control during the study prior to the first dose and for 6 months after 
the last dose. Section 7.7.1 provides a list of effective contraceptive methods for this 
protocol.
10. Willing and able to comply with scheduled visits and study procedures.
7.2.2.
Exclusion Criteria
A patient will be excluded from this study if any of the following criteria are met:
1. History and/or current evidence of clinically significant non-tumor related alteration of 
calcium-phosphorus homeostasis.

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2. History and/or current evidence of clinically significant ectopic 
mineralization/calcification. 
3. History and/or current evidence of clinically significant retinal disorder confirmed by 
retinal examination. 
4. History or current evidence of serious uncontrolled ventricular arrhythmias 
5. Fridericia’s corrected QT interval (QTcF) > 470 ms on ECG conducted during Screening.  
6. Treatment with any of the following within the specified time frame prior to the first dose 
of TAS-120:
a.
Major surgery within the previous 4 weeks (the surgical incision should be fully 
healed prior to the first dose of TAS-120).  
b. Radiotherapy for extended field within 4 weeks or limited field radiotherapy 
within 2 weeks. 
c.
Patients with locoregional therapy, e.g., transarterial chemoembolization (TACE), 
selective internal radiotherapy (SIRT) or ablation within 4 weeks. 
d. Any noninvestigational anticancer therapy within 3 weeks or have not recovered 
from side effects of such therapy prior to TAS-120 administration (mitomycin 
within prior 5 weeks). 
!
Targeted therapy or immunotherapy within 3 weeks or within 5 half-
lives (whichever is shorter) 
e.
Any investigational agent received within 5 half-lives of the drug or 4 weeks, 
whichever is shorter. Concurrent participation in an observational study may be 
allowed after review by the Sponsor’s Medical Monitor.
f.
Patients with prior FGFR-directed therapy.
7. A serious illness or medical condition(s) including, but not limited to, the following:
a.
Known brain metastasis (not including primary brain tumors) unless patient is 
clinically stable for ≥1 month.
b. Known acute systemic infection.
c.
Myocardial infarction, severe/unstable angina, symptomatic congestive heart 
failure (New York Heart Association [NYHA] Class III or IV (see Appendix D,
New York Heart Association [NYHA] Classification) within the previous 2 
months; if > 2 months, cardiac function must be within normal limits and the 
patient must be free of cardiac-related symptoms.
d. Chronic nausea, vomiting, or diarrhea considered to be clinically significant in the 
opinion of the investigator.
e.
Congenital long QT syndrome, or any known history of torsade de pointes, or 
family history of unexplained sudden death. 
f.
Other severe acute or chronic medical or psychiatric condition or laboratory 
abnormality that in the judgment of the investigator would make the patient 
inappropriate for entry into this study.
8. Patients with a history of another primary malignancy that is currently clinically 
significant, and has potential for metastases or currently requires active intervention 
(except for gonadotropin-releasing hormone (GnRH) or luteinizing hormone-releasing 

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hormone (LH-RH) agonists in prostate cancer or adjuvant hormonal therapy in breast 
cancer).
9. Pregnant or lactating female.
7.3.
Discontinuation Criteria
A patient is considered discontinued from study treatment when the decision to permanently stop 
TAS-120 is made. Any TAS-120 discontinuation should be fully documented.
7.3.1.
End of Treatment Discontinuation Criteria
The reason for discontinuation should be documented in the source documents.
Patients can be withdrawn from treatment for the following reasons: 
!
At the patient’s request at any time irrespective of the reason.
!
RECIST-defined disease progression of solid tumors or RANO-defined disease 
progression of brain tumors.
!
Clinical progression.
!
Unacceptable adverse events (AEs), or change in underlying condition such that the 
patient can no longer tolerate therapy, as evidenced by: 
-
A dose delay > 21 days from the scheduled start date of the next cycle.
-
Need for more than the allowed dose reductions of TAS-120 as described in 
Section 8.1.3.1, TAS-120 Dose Reductions for Treatment-emergent Toxicities.
!
Physician’s decision including need for other anticancer therapy not specified in the 
protocol, or surgery or radiotherapy to the only site(s) of disease being evaluated in 
this protocol.
!
Pregnancy.
Upon discontinuation of treatment the investigator is to ensure the following:
!
The Clinical Research Associate (CRA) must be notified immediately; and
!
The Study Treatment Discontinuation Form in the electronic case report form (eCRF) 
must be completed, specifying the primary reason for the patient’s withdrawal from 
the study.
If there is strong evidence of clinical benefit and reasons to justify continuation of TAS-120 
dosing even though treatment discontinuation criteria have been met, this decision must be 
reviewed with the sponsor on a case-by-case basis, and continuation of therapy may be allowed 
assuming all other treatment resumption criteria have been met. Post-study provisions are 
provided in Section 13.4.
7.4.
Patient Numbering and Treatment Allocation
Study sites will enter patient demographic and screening data into the eCRF in order to receive a 
patient number.

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The eCRF will assign each patient a unique patient number.  This patient number will be 
maintained throughout the study and will not be reassigned. Patients who withdraw consent or 
discontinue from the study after being assigned a patient number will retain their initial number. 
Phase 1 Expansion and Phase 2:
Patients will be registered by interactive voice/web response system (IXRS) into Phase 1 
Expansion and Phase 2 parts of the study.  The institutional designee will call/login to the IXRS 
and will enter patient data as outlined in the IXRS Manual. After registration of the enrollment 
visit, the IXRS will assign TAS-120 by kit number, inform the study site user of the kit numbers 
that have been assigned to the patient, and provide instructions for the dispensing of TAS-120. 
Please refer to the IXRS Manual for detailed information.  
If a patient is mistakenly given a kit of TAS-120 that is not the correct kit number as assigned by 
the IXRS, the IXRS help desk must be notified immediately. The reason for the misallocation of 
the study medication must be documented by the study site.
7.5.
Replacement Criteria
No patients will be replaced during the Phase 1 Expansion or Phase 2 parts of the study. 
7.6.
Prohibited Medications and Therapies
Patients are not permitted to receive any other investigational or any other anticancer therapy, 
including chemotherapy, immunotherapy, biological response modifiers, or antineoplastic 
endocrine therapy during the study treatment period.
7.7.
Concomitant Medications and Therapies
The following therapies are permitted:
!
Bisphosphonate
!
Denosumab
!
Concomitant treatment with GnRH agonists or LH-RH agonists is permitted in 
prostate cancer patients.
!
Non enzyme-inducing anticonvulsants such as: Gabapentin (Neurontin), Lamotrigine 
(Lamictal) and Levetiracetam (Keppra).
!
Steroids are allowed for patients with primary brain tumors and brain metastases. 
Steroid use in other patients with other tumor types should be discussed between the 
investigator and the Sponsor’s Medical Monitor.
!
Local or regional palliative cryotherapy or radiation, e.g., for bone pain or palliative 
surgery (non-anti-neoplastic intent).
If, after assessment by the Investigator, radiation for brain metastasis, therapy for bone 
metastasis, or locoregional therapy e.g. local ablation, TACE, SIRT or arterial infusion 
chemotherapy should be initiated for the best benefit of the patient, the patient can start such 
therapy a minimum of 2 days after discontinuation of TAS-120. Consequently, the patient will be 

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censored for the primary endpoint analysis. TAS-120 may be restarted 2 weeks after completion 
of such treatment or when the patient has recovered from the side effects of such treatment.
The following medications/therapies may be given concomitantly under the following 
guidelines: 
Hematologic Support
For Phase 1 Expansion and Phase 2, hematologic support may be administered as medically 
indicated (e.g., blood transfusions, 
, 
erythropoietin stimulating agents) according to the institutional site standards. If there are no 
standard procedures for the use of growth factors, the American Society of Clinical Oncology 
[ASCO] Guidelines for Use of Hematopoietic Colony-Stimulating Factors, available at 
www.asco.org, will be followed.  
Management of Diarrhea
For Phase 1 Expansion and Phase 2, prophylactic treatment for diarrhea is permitted during the 
study if clinically indicated according to the institutional guidelines. If there are no institutional 
standards, refer to the guidelines published by Benson AB, et al in Journal of Clinical 
Oncology.15
Management of Nausea/Vomiting
Antiemetics may be administered as clinically indicated. If there are no institutional standards, 
refer to the ASCO Guidelines for Antiemetics in Oncology.16
Management of Hyperphosphatemia
Phosphate-lowering therapy must be started within 24 hours after observing elevated phosphorus 
(≥5.5 mg/dL [≥ 1.78 mmol/L]). Serum phosphorus is to be tested 4 days (± 24 hours) after 
Day 1 of Cycle 1 to initiate early intervention for hyperphosphatemia. 
Hyperphosphatemia management should follow institutional practice with phosphate binding 
agents, such as Sevelamer, acetazolamide or Fosrenol, or other phosphate binders or a 
combination of these agents. Sevelamer (both tablets and powder) should preferably be taken 
during meals in order to improve gastrointestinal tolerance and compliance. Lanthanum 
carbonate (Fosrenol) should be taken immediately after meals; tablets may be cut if required for 
administration.  Other phosphate binders and hyperphosphatemia treatment drugs may also be 
used. In addition, actively managing constipation by drinking water and following dietary 
guidelines (see Appendix E) may also decrease the risk of hyperphosphatemia.
Refer to Section 8.1.3.1.1 for details on dose interruption or reduction in the management of 
hyperphosphatemia.
Drug interactions with TAS-120
Drug interaction studies have not been conducted in humans. The following information is based 
on results from in vitro studies. Caution is advised if these drugs are given concomitantly (see 
Appendix F, Classification of Substrates, Inhibitors, and Inducers of CYP Enzymes and 
Transporters).
CCI

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Cytochrome P450 (CYP) 3A inhibitors and inducers: CYP3A is involved in the metabolism of 
TAS-120. CYP3A inhibitors and inducers may alter the concentration and activity of TAS-120.
CYP3A substrates: TAS-120 is a potential time-dependent inhibitor of CYP3A. TAS-120 may 
increase the concentration and activity of CYP3A substrates.
P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrates and inhibitors: 
TAS-120 is a substrate of P-gp and BCRP, and a potential inhibitor of P-gp and BCRP. TAS-120 
may alter the PK and activity of P-gp and BCRP substrates. P-gp and BCRP inhibitors may alter 
the concentration and activity of TAS-120.
7.7.1.
Effective Contraception During Study
Female patients who are considered not to be of childbearing potential must have a history of 
being postmenopausal (no menses for 12 months without an alternative medical cause), or 
hysterectomy that is clearly documented in the patient’s source documents.
For WOCBP, including female study participants and partners of male participants, effective 
contraception is required during the trial and for 6 months after the last dose of study medication.
Effective contraception is defined as follows:
!
combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation:
#
oral
#
intravaginal
#
transdermal
!
progestogen-only hormonal contraception associated with inhibition of ovulation:
#
oral
#
injectable
#
implantable
!
intrauterine device (IUD)
!
intrauterine hormone-releasing system (IUS)
!
bilateral tubal occlusion
!
vasectomized partner with documentation of the success of the vasectomy
!
complete abstinence from heterosexual intercourse (periodic abstinence is not a safe 
method)
Male patients with partners who are WOCBP should use a combination of male condom with 
cap, diaphragm, or sponge with spermicide during the trial and for 6 months after the last dose of 
study medication.

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7.8.
Dietary Restrictions
Limitation of phosphate intake including avoidance of foods that are especially high in 
phosphate, e.g., dairy products, meats, nuts, and other high-protein foods, processed foods, and 
colas (e.g., Pepsi) is recommended as part of hyperphosphatemia management. Dietary 
Guidelines for Treatment of Hyperphosphatemia are provided in Appendix E.

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8.
STUDY DRUG
8.1.
Study Drug Administration and Dose Modification Procedures
8.1.1.
Study Drug Administration
TAS-120 is supplied as 4 mg tablets.  The dose for TAS-120 is 20 mg QD. Patients should 
follow the instructions of the treating physician on study drug administration during treatment.
Patients are required to fast for at least 2 hours before and 1 hour after administration of TAS-
120. Patients will be permitted to drink water during this period. Dietary restrictions that limit 
phosphate intake may reduce the risk of hyperphosphatemia (see Section 7.8). On non-PK 
sampling days, TAS-120 can be administered in the morning or evening at the same time (if 
possible) each day. If a patient misses a dose (i.e., did not take TAS-120 for > 12 hours of the 
scheduled time of that day), the patient should take the dose on the next day. 
8.1.2.
Treatment Regimen
TAS-120 will be administered as a daily, continuous, 21-day treatment cycle until at least 1 of 
the criteria for study discontinuation is met. TAS-120 must be administered as outlined in Study 
Drug Administration (Section 8.1.1) and Dose Reduction/Modification Procedures 
(Section 8.1.3). There are no breaks in dosing between cycles. 
8.1.3.
Dose Reduction/Modification Procedures
Dosages will be reduced or modified if AEs are observed according to the criteria described 
below. In the following sections, AE severity grades are based on the National Cancer Institute 
(NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade criteria (version 4.03). 
8.1.3.1.
TAS-120 Dose Reductions for Treatment-emergent Toxicities
Dose reductions must be made according to Table 5. Please note the following:
!
A maximum of 2 dose reductions is permitted 
!
If toxicities requiring further dose reduction recur after the maximum dose reductions 
have been made, or when dose reduction is not permitted as defined in Table 5 the 
patient will be discontinued from study treatment.
Table 5:
TAS-120 Dose Reduction Levels 
1st Dose Reduction
2nd Dose Reduction
Dose Reduce to 16 mg
Dose Reduce to 12 mg 
If dose modification fails to result in achieving minimal criteria to resume treatment, the 
investigator should discontinue the patient from study treatment. 
8.1.3.1.1. Dose Interruption and Modification for Nonhematologic Toxicities
Dosing modifications for nonhematologic toxicities are provided in Table 6. TAS-120 will be 
held when the dose interruption criteria are met. 

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Table 6:
TAS-120 Dosing Modification for Nonhematologic Toxicities
Gradea
Dose Interruption/Resumption
Dose Adjustment 
Grade 1 or 2
Maintain treatment at the same dose 
level, except for Grade 2 elevations of 
bilirubin, AST, and ALT, which should 
be managed as described in Table 9.
None
Grade 3b,c
Suspend treatment until return to 
Baseline or Grade ≤ 1
Reduce by 1 dose levelc from the 
previous level
Grade 4d
Suspend treatment until return to 
Baseline or Grade ≤ 1
Permanent Discontinuation of TAS-120
a.
At the discretion of the investigator, patients may continue/discontinue on TAS-120 at the same dose 
with/without reduction or interruption for AEs (irrespective of grade) considered unlikely to become 
serious or life-threatening (including, but not limited to, fatigue and dry skin).
b.
Except for Grade 3 nausea and/or vomiting controlled by aggressive antiemetic therapy or Grade 3 
diarrhea responsive to antidiarrheal medication which does not require dose hold or dose reduction.
c.
See Table 5 for recommended dose level reductions.
d.
Grade 4 non-hematologic laboratory abnormality: TAS-120 will be permanently discontinued if it is 
assessed by the Investigator as life threatening.
Recommendations for hyperphosphatemia management are provided in Table 7. These are 
suggested guidelines based on emerging data from studies evaluating FGFR inhibitors, and from 
experience of participating investigators. However, clinical judgment from treating physicians 
and local standard practices should be followed to decide the best management for the patient.

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Table 7:
Recommendations for Hyperphosphatemia Management
Serum 
Phosphorus Resulta
(mg/dL and mmol/L)b
Gradec
TAS-120 Dose Interruption and Modification
Recommended phosphate 
binder for the management 
of hyperphosphatemiad
ULN < P < 5.5 (mg/dL)
ULN < P < 1.78 (mmol/L) 
Grade 1
!
No Interruption, consider phosphate binder 
once serum phosphorus level is > ULN
!
Should serum phosphorus level rapidly 
increase within 1 week, consider early 
phosphate lowering therapy, eg, Sevelamer 
oral tablets 800 mg TID
!
800 mg tablets 
Sevelamer TID
!
1600 mg tablets 
Sevelamer TID
!
2400 mg tablets 
Sevelamer TID
!
Acetazolamide 250 mg 
QD (and titrate up to 
BID or TID if required)
!
Lanthanum carbonate 
(Fosrenol) 
1.0 g QD (and titrate up 
to BID or TID if 
required)e
5.5 ≤ P ≤ 7.0 (mg/dL)
1.78 ≤ P ≤ 2.26 (mmol/L)
Grade 2
!
No interruption, implement phosphate 
binder (monotherapy or in combination)
!
Start with Sevelamer monotherapy (range 
from 800 mg TID to 2400 mg TID).
!
Re-assess serum phosphate within 7 days, 
and plan to escalate Sevelamer or add 
treatment with acetazolamide 250 mg QD or 
TID and/or lanthanum carbonate 1.0 g QD 
or TID, and further titration, if phosphate 
level continues to increase.
7.0 < P ≤ 10.0 (mg/dL)
2.26< P ≤ 3.23 (mmol/L)
Grade 3
!
Dose reduce TAS-120 to the next lower 
dose level and intensify phosphate lowering 
therapy.
!
If serum phosphorus level has resolved to 
≤Grade 2 within 14 days after dose 
reduction, continue TAS-120 at the same 
dose level. 
!
If serum phosphorus level not resolved to 
≤Grade 2 after 14 days, further reduce 
TAS-120 from the last reduced dose level 
(or no lower than 12 mg)
!
If serum phosphorus level not resolved to 
≤Grade 2 after 14 days of the second dose 
reduction of TAS-120 (or no lower than 12 
mg), dose interrupt TAS-120 until it is 
resolved to ≤Grade 2 before resuming TAS-
120 at the reduced dose prior to dose 
interruption.
P > 10.0 (mg/dL)
P > 3.23 (mmol/L)
Grade 4
Interrupt TAS-120 until serum phosphorus level 
is resolved to ≤Grade 2, then resume TAS-120 at 
the next lower dose level and intensify phosphate 
lowering therapy. If after 2 dose interruptions 
and 2 dose reductions, serum phosphorus level is 
not resolved to ≤Grade 2 after 14 days, 
permanently discontinue TAS-120.
Abbreviations: BID = twice a day; P = Phosphorus; QD = once a day; TID = three times a day; ULN = upper limit of normal
a.
Serum phosphorus will be tested 4 days (± 24 hours) after Day 1 of Cycle 1 to initiate early intervention for 
hyperphosphatemia.
b.
mmol/L = mg/dL x 0.3229 (conversion factor)  
c.
This grading for the range of serum phosphorus levels will be used for the protocol.
d.
Phosphate binder can be used as monotherapy or in combination. Please consult the drug package insert. Sevelamer 
should be preferably taken in the middle of meals, both tablets and powder, in order to improve gastrointestinal 
tolerance and compliance. If Sevelamer cannot be used, other Phosphate binders or hyperphosphatemia treatment drugs 
can be used. Lanthanum carbonate should be taken instead just after meals – tablets of Fosrenol® are quite big, but can 
be cut if required. No dose adjustments are needed in patients with renal or hepatic impairment. 
e.
Titrate the dose every 2-3 weeks until an acceptable serum phosphate level is reached.

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If there is any uncertainty about continuing therapy or resuming therapy in a patient with Grade 
≥3 nonhematologic AEs, the case must be discussed with the Sponsor’s Medical Monitor prior 
to continuing TAS-120.
8.1.3.1.2. Dose Interruption and Resumption Criteria for Hematologic Toxicities 
Criteria for dose interruption and resumption for hematologic toxicities are described in Table 8. 
Table 8:
TAS-120 Dose Interruption and Modification Criteria for Hematologic 
Toxicities
Recommended Dose Modifications for TAS-120
Worst toxicity
CTCAE Grade (value)
Recommended dose modification any time during a 
cycle of TAS-120
Anemia (Hgb)
Grade 1 (Hgb < LLN - 10.0 g/dL)
Maintain dose level
Grade 2 (Hgb < 10 – 8.0 g/dL)
Maintain dose level 
Grade 3 (Hgb < 8.0 - 6.5 g/dL)
Withhold dose until resolved to ≤ Grade 1 or baseline,
!
If resolved ≤ 7 days, then maintain dose level
!
If resolved > 7 days, then reduce 1 dose level
Grade 4 (life threatening consequences; urgent 
intervention indicated)
Withhold dose until resolved to ≤ Grade 1 or baseline, then 
reduce 1 dose level
Neutropenia (ANC)
Grade 1 (ANC < LLN - 1500/mm3)
Maintain dose level
Grade 2 (ANC < 1500 - 1000/mm3)
Maintain dose level
Grade 3 (ANC < 1000 - 500/mm3)
Maintain dose level
Grade 4 (ANC < 500/mm3)
Withhold dose until resolved to ≤ Grade 2 or baseline,
!
If resolved ≤ 7 days, then maintain dose level
!
If resolved > 7 days, then reduce 1 dose level
Febrile neutropenia (ANC < 1.0 x 109/L, fever ≥ 
38.5°C)
Withhold dose until resolved, then reduce 1 dose level
Thrombocytopenia
Grade 1 (PLT < LLN - 75,000/mm3)
Maintain dose level
Grade 2 (PLT < 75,000 - 50,000/mm3)
Maintain dose level 
Grade 3 (PLT < 50,000 - 25,000/mm3)
Withhold dose until resolved to ≤ Grade 1 or baseline,
!
If resolved ≤ 7 days, then maintain dose level
!
If resolved > 7 days, then reduce 1 dose level
Grade 4 (PLT < 25,000/mm3)
Withhold dose until resolved to ≤ Grade 1 or baseline, then 
reduce 1 dose level
Abbreviations: ANC = absolute neutrophil count; Hgb = hemoglobin; LLN = lower limit of normal; PLT = 
platelets
If the TAS-120 dose is reduced, the dose will not be increased upon resumption.  If a benefit/risk 
assessment favors the increase of dose up to the initial starting dose after dose reduction, an 
agreement with the Sponsor’s Medical Monitor needs to be made prior to the dose increase.
If the toxicities requiring dose reduction as defined above do not recover based on the criteria 
defined in Table 6 through Table 8 within the 21 days of the last dose of TAS-120, the patient 

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will be discontinued permanently from the study. If resumption criteria are met within 21 days of 
the last dose of TAS-120, the patient can resume TAS-120 treatment at the appropriate dose level 
according to instructions provided in Section 9.1.3.1, TAS-120 Dose Reductions for Treatment-
emergent Toxicities.
Treatment-emergent toxicities should be followed until stabilization according to Table 9.
Table 9:
Required Follow-up for Toxicities
Toxicity
Follow-up evaluation
Hematology
If ≥ CTCAE grade 3 neutropenia or ≥ CTCAE grade 3 thrombocytopenia have been 
demonstrated, these parameters must be repeated at least twice a week until resolution 
to ≤ CTCAE grade 1 or baseline to allow for initiation of re-treatment, and then at least 
weekly until either initiation of retreatment or until stabilization.
Renal
If creatinine clearance (calculated* or measured value**) < 30 mL/min has been 
demonstrated, this parameter must be repeated at least twice a week until resolution to 
baseline to allow for initiation of re-treatment, and then at least weekly until either 
initiation of re-treatment or until stabilization. 
Hepatic
If bilirubin ≥ 2 x ULN or ≥ CTCAE grade 3 ALT or AST or the combination of ≥ 
CTCAE grade 2 bilirubin and ≥ CTCAE grade 2 ALT or AST elevation has been 
demonstrated, these parameters must be repeated at least twice a week until resolution 
to ≤ CTCAE grade 1 or baseline to allow for initiation of re-treatment, and then at least 
weekly until either initiation of re-treatment or until stabilization.
Patients with total bilirubin > 1.5 × ULN, or > 3.0 mg/dL for patients with Gilbert’s 
syndrome (any duration) should have fractionation of bilirubin into total/direct or 
indirect/direct components and any additional work-up as clinically indicated by these 
results. Follow-up of hyperbilirubinemia should proceed as per the guidelines above, 
irrespective of the results of fractionation.
Cardiac
If at any time a QTcF > 480 ms and ≤ 500 ms is observed, a cardiology consultation 
must be sought to re-evaluate the abnormal ECG finding.
If at any time a QTcF > 500 ms is observed, 1) Triplicate ECGs (2-3 minutes apart) 
need to be taken approximately 1 hour after the initial ECG. 2) If the mean QTcF is > 
500 ms, the patient must postpone study treatment until a cardiologist has re-evaluated 
the ECG. 3) The re-evaluation of ECG needs to be done as soon as practical but within 
7 days of the initial abnormal ECG. 4) If the cardiologist confirms a mean QTcF > 500 
ms, the patient must be discontinued permanently from study.
Non-
laboratory
Patients who experience non-laboratory Grade 3 or 4 AEs must be evaluated at least 
once a week following demonstration of the resolution of the toxicity to allow for re-
treatment, until stabilization of the toxicity, or until study completion.
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase  
CTCAE = Common Terminology Criteria for Adverse Events; ECG = electrocardiogram; ms = milliseconds; 
QTcF = Fridericia’s corrected QT interval; ULN = upper limit of normal
8.2.
Description and Labeling
8.2.1.
TAS-120
A description and packaging information for the study drug is described in Table 10.

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Table 10:
TAS-120 Product description and packaging information
Product 
Description and 
Dosage Form
Potency/Strength
Appearance
Primary Packaging 
TAS-120 Tablet
4 mg
Round, light yellow, film-coated 
tablet
Aluminum/Aclar blister
8.2.2.
Packaging and Labeling
TAS-120 tablets will be packaged in child-resistant Dosepak® cards.  Labeling will identify 
tablet counts in each card.
The Dosepak® cards will be labeled with at least the following:
a.
Protocol number
b. Sponsor name
c.
Storage conditions
d. Tablet strength
e.
Number of tablets in each container
f.
Investigational caution statement
Additional statements will be printed on the label(s) as required by local regulations.
8.2.3.
Storage
TAS-120 tablets should be stored in accordance with the label.  All study medication must be 
kept in a locked area with access restricted to specific study personnel.
8.2.4.
Patient Instructions for Handling Study Drug
The patient must be instructed in the handling of TAS-120 as follows:
!
To only remove the amount of TAS-120 needed at the time of dosing.
!
Not to remove doses in advance of the next scheduled dosing.
!
To bring all used and unused blister packs to the site at each visit.
!
TAS-120 should be kept in a safe place and out of sight and reach of children.
!
TAS-120 should be taken with a glass of water on an empty stomach (2 hours after 
and 1 hour before a meal).
!
Doses are not to be replaced if the patient misses a dose or vomits a dose and 
administration of study drug should follow the direction of the treating physician. 
!
Patients should make every effort to take doses on schedule.
!
To report any missed doses.
8.3.
Drug Accountability
In accordance with International Council for Harmonisation (ICH) and local regulatory 
requirements, the investigator and/or the person responsible for dispensing investigational drug 

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must be able at all times to account for all investigational product provided to the site. The 
appropriate site personnel must acknowledge receipt of all TAS-120 either by forms included in 
each shipment or via other means (i.e., IXRS). 
Dose reductions, interruptions, and reason for these actions must be recorded in the patient’s 
source documents.
At the conclusion of the study, all used and unused TAS-120 shipped to the investigator must be 
returned to the Sponsor or designated Contract Research Organization (CRO). If on-site 
destruction is required by site policy, such requirements must be documented in the institution’s 
Standard Operating Procedures (SOPs) and provided to the sponsor or its representative for 
review.
No TAS-120 is to be used outside of this study.
8.4.
Blinding
This is an open-label study.  

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9.
STUDY PROCEDURES
The study assessments are described by procedure in the following sections. All information 
required by the protocol must be recorded.
The study schedule must be followed; however, in unavoidable circumstances (e.g., holidays, 
weekends, etc.) a window of ± 3 days is allowable for study procedures as long as the proper 
order of procedures and assessments is maintained. The ± 3-day window does not apply to 
assessments on Day 1 of Cycle 1. 
For computed tomography (CT) scans, a window of ± 2 weeks (up to Cycle 4) or ± 7 days (all 
subsequent cycles) is allowable. These windows are not applicable during Screening. If any 
Screening assessments are repeated on Day 1 of Cycle 1 pre-dose, the site must ensure the 
patient meets the eligibility criteria listed in Section 7.2, Study Population prior to the patient 
taking the first dose of TAS-120.
Note: Procedures performed during screening period within 72 hours prior to dosing on C1D1 do 
not need to be repeated on C1D1.
9.1.
Pre-screening of Tumor Tissue Sample for FGFR2 Gene Fusions or 
other FGFR2 Rearrangements in Patients with iCCA (Phase 2 Only)
Archived or fresh tumor tissue biopsy samples will be tested for FGFR2 gene fusions or other 
FGFR2 rearrangements prior to enrolling patients to the Phase 2 part of the study. 
Patients can be enrolled and treated based on the following:
a.
Testing by Foundation Medicine:
i.
Sent to Foundation Medicine as part of study pre-screening; or
ii.
Already tested by Foundation Medicine; in this case, it is requested that
tumor tissue be sent to Foundation Medicine if available.
b.
Local laboratory testing using next generation sequencing [NGS], fluorescence in situ 
hybridization [FISH], or other assays that can determine FGFR2 gene fusions or other 
FGFR2 rearrangements on tumor tissues or from ctDNA. It is requested that patients 
enrolled on this basis provide tumor tissues to Foundation Medicine, if available from 
either archival samples or fresh tumor biopsy.
Testing may be performed at any time prior to enrollment into the study. Results from the 
testing if not done as part of the TAS-120-101 protocol, must be maintained in the source files at 
the site.
Any AEs or serious adverse events (SAEs) directly associated with a pre-screening procedure 
(i.e., fresh tumor biopsy) should be reported as described in Section 11.1. There is no need to 
record AEs and SAEs that occur between signing the pre-screening consent and full protocol 
consent if they are unrelated to the pre-screening tumor biopsy procedure unless it is mandatory 
by local regulations.
Tumor samples may be stored at the Sponsor’s designated central laboratory for up to 10 years 
following completion of the study, to enable companion diagnostic research.

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9.2.
Informed Consent
A signed and dated ICF will be obtained from the patient as required by the protocol before any 
main screening procedures are conducted. A signed copy of the ICF will be given to the patient.  
Multiple ICFs covering different procedures will be required based upon local requirements.
9.3.
Medical History
A complete medical history will be obtained during Screening within 28 days prior to first 
TAS-120 administration on Day 1 of Cycle 1.
Existing signs and symptoms will be obtained during screening (within 28 days prior to TAS-120 
administration on Day 1 of Cycle 1), and reviewed on Day 1 of Cycle 1 (within 24 hours of 
dosing).  If evaluation of signs and symptoms is performed during the screening period within 
72 hours prior to dosing, the assessment does not need to be repeated on C1D1.
9.4.
Physical Examination
A complete physical examination will be performed at the time points listed below.
!
Screening (within 28 days prior to TAS-120 administration on Day 1 of Cycle 1).
!
Within 24 hours prior to TAS-120 administration on Day 1 of each cycle.  Note that 
procedures performed during the screening period within 72 hours prior to dosing do 
not need to be repeated on C1D1.
!
At end of treatment (+0-7 days).
!
30-day safety follow-up visit.  
9.5.
Height, Vital Signs, and Weight
The patient’s height will be obtained only during Screening within 28 days prior to TAS-120 
administration on Day 1 of Cycle 1.
The patient’s vital signs (blood pressure, heart rate, body temperature, and respiration rate) and 
body weight will be collected at the time points listed below. All vital signs are to be obtained 
with the patient in a position that is consistent for all time points for each patient.
!
Screening (within 28 days prior to TAS-120 administration on Day 1 of Cycle 1).
!
Within 24 hours prior to TAS-120 administration on Day 1 of each cycle. Note that 
procedures performed during the screening period within 72 hours prior to dosing do 
not need to be repeated on C1D1.
!
At end of treatment (+0-7 days).
!
30-day safety follow-up visit.
9.6.
Performance Status
An ECOG Performance Status score (see Appendix C ECOG Performance Status) will be 
obtained at the following time points:

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!
Screening (within 28 days prior to first TAS-120 administration on Day 1 of Cycle 1).
!
Within 24 hours prior to TAS-120 administration on Day 1 of each cycle.  Note that 
procedures performed during the screening period within 72 hours prior to dosing do 
not need to be repeated on C1D1.
!
At end of treatment (+0-7 days).
!
30-day safety follow-up visit.
9.7.
Electrocardiogram
A 12-lead resting ECG will be performed at the following time points:
!
Screening (within 28 days prior to TAS-120 administration on Day 1 of Cycle 1). 
!
Two hours (± 15 min) after TAS-120 dose on Day 1 of Cycle 1.
!
For all subsequent cycles starting with Cycle 2, ECG should be performed on Day 1 
(± 3 days) of each cycle obtained 2 hours (± 15 min) after the TAS-120 dose.
!
At end of treatment (+0-7 days).
!
30-day safety follow-up visit.
9.8.
Ophthalmological Examination
Ophthalmological examination will be performed at the following time points: 
!
Screening within 28 days prior to TAS-120 administration on Day 1 of Cycle 1.
!
4-6 weeks after starting treatment with TAS-120
!
Any other time due to local requirements, physician judgement and/or symptoms or signs 
of mineral deposits.
!
At end of treatment (+0-7 days)
!
30-day safety follow-up visit.
The cornea and conjunctiva are readily visible tissues, and therefore, abnormalities of the cornea 
and conjunctiva can usually be recognized via external ocular examination and routine slit lamp 
biomicroscopy. The ophthalmologic examination will encompass the following:
1. External ocular examination.
2. Routine slit lamp biomicroscopy of anterior ocular structures (Fluorescein or rose Bengal 
or other dyes used to evaluate the ocular surface can be used according to institutional 
guidelines and local clinical practice).
3. Retinal exam to evaluate the anterior and posterior chamber
The examination will be repeated, if clinically indicated, and the repeat examination will include 
the same testing employed at Screening in addition to any other clinically indicated examination.

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9.9.
Neurological Examination
Neurological examination will be performed at the following time points for all patients:
!
Screening (within 28 days prior to TAS-120 administration on Day 1 of Cycle 1).
!
Any other time due to local requirements, physician judgement and/or symptoms or signs 
of mineral deposits.
!
At end of treatment (+0-7 days)
!
30-day safety follow-up visit.
The basic neurologic examination should follow institutional guidelines and local clinical 
practice, and will encompass testing of:
!
Cranial nerves II-XII.
!
Muscular strength of upper and lower extremities.
!
Deep tendon reflexes of upper and lower extremities.
This examination will be repeated, if clinically indicated, and the repeat examination will include 
the same testing employed at Screening in addition to any other clinically indicated examination.
9.9.1.
Neurological Examination as part of RANO Evaluation for Patients with 
Primary CNS Tumors
For patients with primary CNS tumors, a complete neurological examination will include 
assessment of level of consciousness, mental status, speech, vision fundus (papilledema), cranial 
nerves III, IV, VI, cranial nerves other, motor, sensory, and gait or limb ataxia. An overall score 
according to a 6-point scoring code will be determined for each finding and recorded in the 
eCRF. Follow-up evaluation of the neurological examination will be based on any changes in the 
neurological clinical examination from the previous exam. Changes should be unrelated to 
postictal state or other unrelated events such as infection.
Neurological examination must always be performed at screening and within one week of the 
date of the Gd-MRI as part of the response assessment for patients with brain tumor.
Scoring code for each neurological finding: 
0 = Normal
1 = Slightly or minimally abnormal
2 = Moderately abnormal
3 = Severely abnormal
4 = Grave
5 = Not able to record
Grading scale to designate relative changes:
+2 = definitely better
+1 = possible better

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0 = unchanged
-1 = possible worse
-2 = definitely worse
9.10.
Clinical Laboratory Evaluations
Blood samples for hematology, coagulation, and chemistry assessments will be collected and 
measured as described in Section 9.10.1 and Section 9.10.2, respectively. Laboratory 
assessments obtained prior to signing of the ICF may be used as screening laboratory values if 
they were obtained within 28 days prior to TAS-120 administration on Day 1 of Cycle 1.
All laboratory results must be reviewed for clinically significant events. Any clinically 
significant events must be followed and reported as required by the protocol (see Section 11.1, 
Adverse Events/Serious Adverse Events and Section 11.2, Laboratory Evaluations). 
9.10.1.
Hematology and Coagulation
Blood for hematology and coagulation assessments will be collected at the following time points 
and when clinically indicated:
!
Screening (within 7 days prior to first TAS-120 administration on Day 1 of Cycle 1).
!
Obtain within 24 hours before TAS-120 administration on Day 1 of each cycle, and 
anytime on Day 8 and Day 15 of Cycle 1.  Note that procedures performed during the 
screening period within 72 hours prior to dosing do not need to be repeated on C1D1.
!
At end of treatment (+0-7 days)
!
30-day safety follow-up visit.
In addition, the criteria for repeat testing listed in Section 11.2.2, Repeat Testing, will be 
followed as needed.
The following hematology and coagulation parameters will be measured: 
Red blood cell (RBC) count
White blood cell (WBC) count with differential
Hemoglobin 
Neutrophils1
Hematocrit
Lymphocytes
Platelets
Monocytes
International normalized ratio 
(INR)
Eosinophils
Activated partial thromboplastin 
time (APTT)
Basophils
1 Includes both segmented and band neutrophils.

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9.10.2.
Chemistry
Blood (serum or plasma) will be collected at the following time points for serum chemistry 
assessments:
!
Screening (within 28 days prior to first TAS-120 administration on Day 1 of Cycle 1).
!
Obtain within 24 hours before TAS-120 administration on Day 1 of each cycle, and 
anytime on Day 8 and Day 15 of Cycle 1.  Note that procedures performed during the 
screening period within 72 hours prior to dosing do not need to be repeated on C1D1.
!
Phosphorus is to be tested 4 days (±24 hours) after Day 1 of Cycle 1 to initiate early 
intervention for hyperphosphatemia.
!
As clinically indicated by the investigator or if previous chemistries showed an 
elevation of phosphorus that required action as specified in Section 8.1.3.1.1.
!
At the end of treatment (+0-7 days).
!
30-day safety follow-up visit.
In addition, the criteria for repeat testing listed in Section 11.2.2, Repeat Testing, will be 
followed as needed.
The following chemistry parameters will be measured:
Table 11:
Laboratory Assessments for TAS-120-101
Alanine 
aminotransferase (ALT)
Blood urea nitrogen (BUN) or 
Urea
Creatinine kinase (CK)
Aspartate 
aminotransferase (AST)
Phosphorus
Troponin I or T (quantitative)c
Alkaline phosphatase
Calcium
Total bilirubinb
Chloride
Glucose
Sodium
Creatinine clearancea
Potassium
a Calculated (Ccr) or measured creatinine clearance.
b Fractionation of bilirubin (= direct/indirect bilirubin or conjugated/unconjugated) must be performed/calculated in 
case of an elevation of total bilirubin. 
C Quantitative evaluation of either Troponin I or Troponin T (not both) required at each time point.  Evaluation of the 
same parameter (Troponin I or Troponin T) at different timepoints for the same patient is not required.

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9.10.3.
Urinalysis
Urine samples for qualitative analysis (“urine dipstick”) will be collected at the time points listed 
below:
!
Screening (within 28 days prior to first TAS-120 administration on Day 1 of Cycle 1).
!
Within 24 hours prior to TAS-120 administration on Day 1 of each cycle.  Note that
procedures performed during the screening period within 72 hours prior to dosing do 
not need to be repeated on C1D1.
!
At end of treatment (+0-7 days).
!
30-day safety follow-up visit.
In addition, the criteria for repeat testing listed in Section 11.2.2, Repeat Testing, will be 
followed as needed.  At all time-points, urinalysis should include:
!
PH
!
Specific gravity
!
Protein
!
Glucose
!
Ketones
!
Blood
!
Leukocyte esterase
!
Nitrite with microscopic examination if indicated
9.12.
Pregnancy Test
For patients who are WOCBP, pregnancy testing by assessment of serum beta-human chorionic 
gonadotropin (∃-HCG) will be conducted:
!
At screening (28 days prior to the first administration of TAS-120); and
!
At end of treatment (+0-7 days).  
Serum or urine pregnancy test is also required: 
CCI

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!
Within 24 hours prior to TAS-120 administration on Day 1 of each cycle, or additionally 
according to local requirements.  Note that procedures performed during the screening 
period within 72 hours prior to dosing do not need to be repeated on C1D1.
!
30-day safety follow-up visit.
The date, time, and test results will be recorded in the patient’s source documents.
Female patients who are not considered to be of child-bearing potential must have a history of 
being post-menopausal (no menses for 12 months without an alternative medical cause), surgical 
sterilization, or hysterectomy that is clearly documented in the patient’s source documents. 
9.13.
Pharmacokinetic Sample Collection
9.13.1.
Optional Pharmacokinetic Sample Collection for Phase 1 Expansion
For all patients in the Phase 1 Expansion, optional blood PK samples (a minimum of 1 mL) may 
be collected per the investigator’s discretion in any patient at the following time points: prior to 
dosing (0 hour) and post-dose at 1, 2, 3, 4, 6, and 24 hours (± 10 minutes). The 24-hour 
post-dose sample should be collected prior to next TAS-120 administration. These optional 
blood PK samples could be collected on any day in Cycle 1 and Cycle 2 when PK should be 
collected as part of the safety evaluation.
For patients in the Phase I Expansion with primary CNS tumors only, optional blood and CSF 
samples will be collected 2-4 hours post-dose on Day 1 of Cycle 2 to assess the TAS-120 
concentration ratio of CSF to plasma. Blood and CSF samples must be collected at the same 
time point (within 15 minutes).  A minimum of 1 mL each of whole blood and CSF will be 
collected for the PK analysis.
Blood and CSF samples for PK evaluation will be collected and processed according to 
instructions provided in the Laboratory Manual.  
9.13.2.
Pharmacokinetic Blood Sample Collection for Phase 1 Expansion/Phase 2
During Phase 1 Expansion and Phase 2, blood samples of TAS-120 will be collected on Day 1 of 
Cycle 2 pre-dose, 1 h ± 30 min. and 3 h ± 30 min. post-dose to assess the plasma exposure at 20 
mg QD.  In addition, blood samples will be collected on Day 1 of Cycle 3 and Cycle 4 pre-dose. 
A minimum of 1 mL of whole blood will be collected for the PK analysis per Table 12. The total 
blood volume collected for the PK samples will be approximately 5 mL per patient. 
Blood samples for PK evaluation will be collected and processed according to instructions 
provided in the Laboratory Manual.  

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Table 12:
Pharmacokinetic Blood Sample Collection for Phase 1 Expansion/
Day of Study
Collection Time Point (hours 
[h]) in Relation to TAS-120 
Administration (Time 
Window)
Blood Volume 
Day 1 of Cycle 2
pre-dose
1 mL
1 h ± 30 min post-dose
1 mL
3 h ± 30 min post-dose
1 mL
Day 1 of Cycle 3
pre-dose
1 mL
Day 1 of Cycle 4
pre-dose
1 mL
Total volume per patient
Approximately 5 mL
h = hour
9.14.
ctDNA Analysis of FGF/FGFR Aberrations 
9.14.1.
ctDNA from Blood Sample for the Analysis of FGF/FGFR Aberrations 
For the Phase 1 Expansion and Phase 2, a blood sample will be collected to assess FGF/FGFR 
aberrations in ctDNA at Screening within 28 days prior to the first TAS-120 administration on 
Day 1 of Cycle 1 (required) and at the EOT visit (optional). A minimum of 20 mL of whole 
blood will be collected at each time point. This sample is being collected for exploratory analysis 
to evaluate FGF/FGFR aberrations in circulating blood and for future clinical development. 
Sample collection and preparation will be according to instructions provided in the Laboratory 
Manual.
9.15.
Prior and Concomitant Medications and Therapies 
All therapies and medications, prescription and over-the-counter, will be collected from the time 
the main study ICF is signed through the 30-day safety follow-up visit, including any medication 
used to treat AEs or SAEs during the 30-day follow-up period. Use of concomitant medication 
and/or therapy should be documented in the patient’s source documents. In addition, the time of 
initiation of new anticancer therapy received during the 30-day follow-up period will be 
collected.
9.16.
Adverse Event Assessment
Patients will be monitored for any untoward medical events (AEs or SAEs) from the time the 
main study ICF is signed through 30 days after last dose of TAS-120 or until the start of new 
antitumor therapy, whichever is earlier.  For the Phase 2 part of the study, any AEs or SAEs that 
occur after the signing of pre-screening consent and are directly associated with a pre-screening 
procedure (i.e., fresh tumor biopsy) should be reported as described in Section 12.1. For AEs and 
SAEs that occur between signing the pre-screening consent and main study ICF, there is no need 
to record those that are unrelated unless it is mandatory by local regulations.
Serious AEs should be reported to Taiho Oncology, Incorporated (TOI) Pharmacovigilance or its 
designee. If serious medical occurrences or deaths outside the 30-day follow-up period are 
CCI

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reported to or observed by the investigator that he/she believes are related to the administration 
of the TAS-120, it is the investigator’s responsibility to report this occurrence to TOI 
Pharmacovigilance or its designee. See Section 11.1.1, Adverse Events, and Section 11.1.2, 
Serious Adverse Events, for definitions and detailed reporting of AEs and SAEs.
9.17.
Tumor Assessments/Scans
9.17.1.
Tumor Assessment for Advanced Solid Tumors
Tumor assessments/imaging studies of the chest, abdomen, and pelvis (as clinically indicated) 
must be obtained at each time point listed below for all patients with solid tumors.
!
Screening within 28 days prior to Day 1 of Cycle 1. Computed tomography scans 
obtained prior to the signed ICF may be used as the screening scan if they were 
obtained within 28 days of the first dose of TAS-120.
!
At the end of every 2 cycles (up to +2 weeks), up to Cycle 4.
!
Following Cycle 4, at least after every 3 cycles (± 7 days) or as clinically indicated, 
until documented progression (including after end of treatment if the patient 
discontinues for reasons other than radiologic disease progression).
!
At end of treatment (+0-7 days), a CT scan must be performed if the prior scan was 
performed ≥ 9 weeks prior to discontinuation of TAS-120 treatment if the patient 
discontinued for reasons other than radiologic disease progression.
On-site tumor assessments will be performed by the investigator/local radiologist according to 
RECIST guidelines (version 1.1, 2009). Results of these assessments, including response for 
target and non-target lesions and appearance of new lesions, will be the basis for the continuation 
or discontinuation of TAS-120. Response definitions are provided in Section 10, Efficacy 
Assessment Criteria.
If the investigator determines that a patient has developed clinical progression manifested by 
symptomatic deterioration but not supported by radiologic evidence of progression, the patient 
should stop treatment. Symptoms of clinical progression must be documented in the patient’s 
source documents and must be reported as AEs. Every effort should be made to document 
objective progression even after discontinuation of treatment.
The same method of assessment and the same technique must be used to characterize each 
identified and reported lesion at Screening, throughout the study, and during the follow-up 
period.
On-site tumor assessments will be conducted. Tumor assessment scans from patients with iCCA 
treated at 16, 20 and 24 mg QD and patients with primary brain tumors may also be 
prospectively or retrospectively collected and forwarded to the core imaging laboratory.  
If a patient in Phase 1 Expansion or Phase 2 has a response, response confirmation should be 
obtained through tumor assessments/scans 4 to 6 weeks after the first documentation of response. 
Patients must then return to their original schedule of assessments (i.e., every 2 cycles [or every 
3 cycles after Cycle 4]).

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9.17.2.
Tumor Assessment for Brain Tumors
Patients will be evaluated for response by Gd-MRI. All Gd-MRIs (standard brain tumor MRI 
including both precontrast and postcontrast images using a Gadolinium (Gd) chelate as the 
contrast agent) should be performed when the patient is on a stable dose of steroids for at least 7 
days. Gd-MRI will be performed at the following time points: 
!
Screening within 28 days prior to Day 1 of Cycle 1. Gd-MRI scans obtained prior to 
the signed ICF may be used as the screening scan if they were obtained within 28 
days of the first dose of TAS-120.
!
At the end of every 2 cycles (up to +2 weeks), up to Cycle 4, until documented 
progression (including after end of treatment if the patient discontinues for reasons 
other than radiologic disease progression).
!
Following Cycle 4, at least after every 3 cycles (± 7 days) or as clinically indicated.
!
At end of treatment (EOT), a Gd-MRI scan must be performed if the prior scan was 
performed ≥ 9 weeks prior to discontinuation of TAS-120 treatment if the patient 
discontinued for reasons other than radiologic disease progression.
If a patient has a response, response confirmation should be obtained through tumor 
assessments/scans 4 to 6 weeks after the first documentation of response. Patients must then 
return to their original schedule of assessments.
Neurological examination for patients with brain tumors must always be performed within one 
week of the date of the Gd-MRI as part of the response assessment. Response will be based on 
RANO criteria.
All patients’ files and radiological assessments must be available for source verification and may 
be submitted for extramural review for final assessment of antitumor activity. Results of any 
unscheduled evaluations should be recorded in the patient’s source documents.
9.18.
Patient-Reported Outcomes
Two Patient-Reported Outcome (PRO) instruments, EuroQol-5D measure of health-related 
quality of life (EQ-5D) and the European Organization for Research and Treatment of Cancer 
Quality of Life Questionnaire (EORTC QLQ-C30) will be used in the Phase 2 part of the study.  
EQ-5D is a standardized measure of health status as patient-reported outcome assessment.  
EORTC QLQ-C30 is an integrated system for assessing the health-related quality of life of 
cancer patients participating in international clinical trials. These assessments will be collected at 
the following time points (as close as possible to the time points when tumor assessment is 
performed):
!
Screening within 28 days prior to Day 1 of Cycle 1. 
!
At the end of every 2 cycles (up to +2 weeks), up to Cycle 4.
!
Following Cycle 4, at least after every 3 cycles (± 7 days) or as clinically indicated.
!
At end of treatment (EOT)

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9.19.
End-of-treatment Visit
An end-of-treatment (EOT) visit is required for all living patients who discontinue treatment.  
The EOT visit must be performed 0-7 days after the decision is made to discontinue study 
treatment (for patients who discontinue at a planned study visit, that visit may be considered the 
EOT visit if all assessments required at EOT are performed). 
9.20.
30-Day Safety Follow-up
A safety follow-up visit will be conducted 30 days after the last dose of TAS-120. If the patient 
starts new anticancer therapy within 30 days of the last dose of TAS-120, the 30-day safety 
follow-up visit should be performed prior to the start of new anticancer therapy within the 
30-day window. If the evaluation of EOT and 30-day Safety Follow-up is within ± 14 days, only 
the 30-day Safety Follow-up will be performed. If the patient is unable to return to the site prior 
to the initiation of new treatment, a follow-up phone call can be conducted by the site to collect 
any new safety information that occurred between discontinuation of study treatment and the 
initiation of the new anticancer treatment.
9.21.
Survival Status Follow-up
Overall survival status will be collected during the survival follow-up period every 3 months 
(±2 weeks) from the patient’s previous visit.  
For the Phase 1 Expansion part of the study, patients should be followed for up to 12 months 
after the last patient enrolled in this phase of the study. 
For Phase 2, patients should be followed for up to 18 months after the last patient enrolled in this 
part of the study. 
CCI

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10.
EFFICACY ASSESSMENT CRITERIA
10.1.
Efficacy Assessment for Solid Tumors
The determination of antitumor efficacy will be based on objective tumor assessments made by 
the investigator according to the revised RECIST guidelines (version 1.1, 2009) of 
unidimensional evaluation.17
For Phase 1 Expansion, the primary endpoint is ORR (and EPR for GBM or grade III glioma) 
and the secondary endpoints of DOR, DCR, PFS, and OS. 
For Phase 2, the primary endpoint is ORR and the secondary endpoints of DOR, DCR, PFS, 
PROs and OS.
Primary endpoints will be based on the independent review of images by the Core Imaging 
Laboratory.  In addition, for the Phase 2 part of the study, sensitivity analyses for some key 
efficacy endpoints (eg, ORR, and PFS) will be performed based on investigators or local 
radiologist assessments.  
The RECIST guideline (version 1.1, 2009) instructs those conducting oncology trials designed 
with a primary endpoint that is response-related to require confirmation of response after a 
minimum of 4 weeks.
10.1.1.
Method of Imaging
All patients with and without measurable disease will be eligible for assessment. The same 
method of assessment and the same technique should be used to characterize each identified and 
reported lesion at Screening and during follow-up. Imaging-based evaluation is preferred to 
evaluation by clinical examination when both methods have been used to assess the antitumor 
effect of treatment. All measurements should be recorded in metric notation using a ruler or 
calipers.
Contrast enhanced CT scans or MRIs are the preferred methods for tumor assessments. If a 
contrast agent is contraindicated in a patient, obtain a non-contrast chest CT and enhanced MRI 
of the abdomen (and pelvis if clinically indicated). A spiral CT should be performed using a 
5 mm or less contiguous reconstruction algorithm. Images must be acquired of the chest and 
abdomen (and pelvis if clinically indicated or obtained at Baseline) at each time point. Only CT 
scans and MRI may be used for tumor measurement.
Clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules, 
palpable lymph nodes). In the case of skin lesions, documentation by color photography, 
including a ruler to estimate the size of the lesion, is recommended.
Ultrasound should not be used to measure tumor lesions that are clinically not easily accessible 
for overall response evaluation (e.g., visceral lesions). Ultrasound is a possible alternative to 
clinical measurements of superficial palpable nodes, subcutaneous lesions, and thyroid nodules. 
Ultrasound might also be useful to confirm the complete disappearance of superficial lesions 
usually assessed by clinical examination.
For additional guidance refer to the revised RECIST guidelines (version 1.1, 2009)17
specifications for standard anatomical radiological imaging, which are included in the Imaging 
Manual.

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10.1.2.
Tumor Definitions
Measurable Lesions:
!
Measurable visceral lesions: Lesions that can be accurately measured in at least 
1 dimension with the longest diameter (to be recorded) ∀10 mm by CT scan if using 
slice thickness of 5 mm or less, or at least double the slice thickness of the CT or MRI 
scan if the slice thickness is > 5 mm.
!
Measurable pathological lymph nodes: A malignant lymph node must be considered 
pathologically enlarged with high suspicion of metastasis and measure ∀15 mm in 
the short axis when assessed by CT scan. The short axis is defined as the longest 
linear dimension perpendicular to the node’s longest diameter as assessed within the 
same plane that the scan was acquired.
Only measurable lesions can be selected as target lesions.
Non-measurable lesions include:  
!
Small visceral metastatic lesions that have a longest dimension less than 10 mm, or if 
slice thickness is greater than 5 mm, less than twice the slice thickness. 
!
Abnormal and suspected metastatic lymph nodes that are ≥ 10 mm to < 15 mm in the 
short axis.
!
Truly non-measurable lesions (e.g., ascites and peritoneal carcinomatosis).
All non-measurable lesions can only be selected as non-target lesions.
Target Lesions:
!
All measurable lesions up to a maximum of 2 lesions/organ and 5 lesions in total, 
representative of all involved organs/tissues should be identified as target lesions.
!
Target lesions should be selected on the basis of their size (visceral lesion with the 
longest diameter and lymph node with the measurement of short axis), be 
representative of all involved organs/tissues, but in addition should be those that lend 
themselves to reproducible repeated measurements.
!
When recording tumor measurements, the longest diameter will be measured for each 
non-nodal target lesion. For measurable pathological lymph nodes that may be 
identified as target lesions, the short axis measurement will be combined with the 
measurements of non-nodal (i.e., visceral lesion) target lesions. Therefore, in cases of 
complete response (CR) when abnormal nodes have been used as target lesions, the 
sum of diameters will not reduce to a null value.
!
Target lesions will be followed up and measured at each subsequent time point.
!
The sum of the diameters for all target lesions will be calculated and recorded. The 
baseline sum will be used as a reference to further characterize any objective tumor 
assessment in the measurable dimension of the disease.

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!
Assign a measurement to all target lesions regardless of size. An option of “too small 
to measure” will be provided if a measurement cannot be assigned. A value of zero 
should only be assigned in the case of a CR.
!
An option of “not assessable” for a lesion will only apply to lesions that that cannot 
be read due to technical reasons, for example:
1. CT artifact.
2. Patient positioning where the lesions are obstructed or cannot be seen.
3. Lesions that may not be seen in their entirety due to CT slice thickness.
!
In cases where a lesion divides into 2 lesions, the longest diameters of the fragmented 
portions should be added together to calculate the target lesion sum.
!
In cases where 2 lesions coalesce, a plane between them may be maintained that 
would aid in obtaining maximal diameter measurements of each individual lesion. If 
the lesions have truly coalesced such that they are no longer separable, the vector of 
the longest diameter in this instance should be the maximal longest diameter for the 
“coalesced lesion.”
Non-target Lesions:
Non-target lesions include all non-measurable lesions and measurable lesions that have not been 
selected as target lesions.
The primary lesion should always be classified as a non-target lesion irrespective of its size and 
whether or not it can be accurately measured.
Lymph nodes that have a short axis < 10 mm are considered non-pathological and should not be 
recorded.
Any equivocal lesion without clear diagnosis (e.g., uncharacteristic solitary lung nodule without 
biopsy, uncharacteristic thyroid mass lesion without fine needle aspiration) may be considered a 
non-target lesion if it cannot be differentiated from a benign lesion.
All other lesions (or sites of disease), including pathological lymph nodes, should be identified as 
non-target lesions and should also be recorded at Baseline. Measurements are not required, but 
their presence, absence, or unequivocal progression should be followed throughout the study.
It is possible to record multiple non-target lesions involving the same organ as a single item on 
the eCRF (e.g., multiple enlarged pelvic lymph nodes or multiple liver metastases).
10.1.3.
Response Criteria
On-site assessments will include the assessment of:
!
Target and non-target tumor responses
!
Objective response
The above assessments will be made as per the time points identified in Section 9.17, Solid 
Tumor Assessments/Scans.

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10.1.3.1.1. Additional Criteria to Consider When Making Tumor Response Assessments
When effusions are known to be a potential adverse effect of treatment, cytological confirmation 
of the neoplastic origin of any effusion that appears or worsens during treatment when the 
measurable tumor has met criteria for response or SD is not mandatory, but might be performed 
to differentiate between response (or SD) and PD when substantial change of effusion and or 
ascites is noted.
If a patient is discontinued from the study before PD occurs and receives local or regional 
palliative radiotherapy during the follow-up period, the irradiation site must be omitted from the 
response assessment of the patient; however, if the site is observed to demonstrate disease 
progression, this case should be judged as PD.
For equivocal findings of progression (e.g., very small and uncertain new lesions; cystic changes 
or necrosis in existing lesions), treatment may continue until the next scheduled assessment. If at 
the next scheduled assessment, progression is confirmed, the date of progression should be the 
earlier date when progression was suspected. 
10.1.3.2.
Objective Response Assessment
Assessments will be based on the definitions provided in Table 13 and Table 14.
Table 13:
Time Point Response for Patients with Target (+/- Non-Target) Disease
Target Lesions
Non-Target Lesions
New Lesions
Objective Response
CR
CR
No
CR
CR
Non-CR/Non-PD or Not 
all evaluated
No
PR
PR
Non-PD or Not all 
evaluated
No
PR
SD
Non-PD or Not all 
evaluated
No
SD
Not all evaluated
Non-PD
No
Not evaluable
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
Abbreviations: CR = complete response; PD = progressive disease; PR = partial response; SD = stable
disease

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Table 14:
Time Point Response for Patients with Only Non-Target Disease
Non-Target Lesions
New Lesions
Objective Response
CR
No
CR
Non-CR/Non-PD
No
SD
Not all evaluated
No
Not evaluable
Unequivocal PD
Yes or No
PD
Any
Yes
PD
Abbreviations: CR = complete response; PD = progressive disease; SD = stable disease
10.1.4.
Best Objective Response Assessment for Solid Tumors
The best objective response for solid tumors will be assessed as defined in the Statistical 
Analysis Plan (SAP) per RECIST guideline (version 1.1, 2009). To be assigned a status of PR or 
CR for Phase 1 Expansion and Phase 2, changes in tumor measurements in patients with 
responding tumors must be confirmed by repeat studies that should be performed at 4 weeks 
after the criteria for response are first met. On the other hand, confirmation is not required for 
Phase 1 Dose Escalation. In the case of SD, measurements must have met the SD criteria at least 
once after study entry at a minimum interval of 6 weeks across the phases.
10.2.
Efficacy Assessment for Brain Tumors
10.2.1.
Method of Imaging
Patients with brain tumors will be evaluated for response by contrast MRI (e.g., Gd-MRI). All 
MRIs should be performed when the patient is on a stable dose of steroids. Gd-MRI will be 
performed at screening, end of every 2 cycles (up to + 2 weeks) in the first 4 cycles and every 
3 cycles (± 7 days) thereafter and at study completion for tumor measurements.  For patients who 
discontinued treatment for reasons other than disease progression, tumor assessments should be 
continued until radiologic disease progression or initiation of new anticancer therapy (whichever 
occurs first).
10.2.2.
Tumor Definitions
10.2.2.1.
Measurable and Non-measurable Contrast Enhancing Lesions
Measurable Lesions/Target Lesions
To evaluate changes in brain tumors using the RANO criteria, weighted images will be measured 
and monitored for response over time for up to 5 enhancing lesions identified on baseline T1 (T1 
relaxation time constant). In general, the largest enhancing lesions that lend themselves to 
repeated measurements will be selected as target lesions (see Figure 4).  Selected target lesions 
will demonstrate contrast enhancement, have clearly defined margins, have two perpendicular 
diameters of at least 10 mm, and be visible on two or more axial slices that are at most 5 mm 
apart with no interslice gap.  If slices were thicker than 5 mm, the selected lesions should 
measure two times the slice thickness on the baseline scan. To perform the size measurement, the 

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maximal tumor diameter will be obtained with a second diameter obtained at a right angle to the 
first. The product of these measurements will be used for purposes of comparison between 
imaging time points. 
Figure 4:
Algorithm for Selection of Target Lesions:  RANO Criteria
Non-measurable Lesions
Non-measurable lesions are generally those that do not meet the above criteria. Tumors around a 
cyst or surgical cavity will also be considered non-measurable unless a nodular component 
measuring 10 mm or greater in diameter is present.  
10.2.2.2.
Non-enhancing Lesions 
Non-enhancing lesions visualized with T2-weighted fluid-attenuated inversion recovery 
(T2/FLAIR) will also be assessed when evaluating tumor response. Non-enhancing lesions will 
not be measured, but instead will be monitored for changes in size. It is important to note that the 
extent of the non-enhancing component of the tumor can be difficult to determine since localized 
swelling and damage caused by radiation have a similar radiographic appearance. Changes in 
T2/FLAIR signal that suggest presence of an infiltrating tumor include mass effect, infiltration of 
the cortical ribbon, and location outside of the radiation field.  
10.2.3.
Response Definitions
Brain tumor response to therapy will be categorized into one of four categories: complete 
response, partial response, stable disease, or progression.  
Enhancing
Non-measurable
(At least 1 diameter <10 mm)
Non-target
Non-enhancing
(Seen on T2/FLAIR)
Measurable
(2 perpendicular diameters ≥10 mm)
Non-target
Non-target
Target
Up to 5:
!
Largest
!
Reproducible
The others
All tumor lesions

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Complete Response
Complete response (CR) will be achieved if all enhancing (measurable and non-measurable) 
lesions have disappeared for at least 4 weeks, there are no new lesions, and non-enhancing 
lesions have either improved or remain stable. Clinically, subjects must be off corticosteroids (or 
be receiving only physiological replacement doses) and show stable or improved clinical 
symptoms.  
Partial Response
Partial response (PR) will be achieved when all of the following requirements are met: the sum 
of the products of perpendicular diameters of all enhancing lesions is reduced by 50% or more 
(from baseline) for at least 4 weeks, there are no new lesions, there is no progression in non-
measurable lesions, and non-enhancing lesions have either improved or remain stable. Clinically, 
subjects must be on a corticosteroid dose no greater than the dose they were receiving at the time 
of the baseline scan and they must show stable or improved clinical symptoms.  
Stable Disease
A subject will be considered to have stable disease (SD) if all of the following are met: the 
subject does not qualify for complete response, partial response, or progressive response 
(described below), and non-enhancing T2/FLAIR lesions are stable. Subjects must be on either a 
lower dose of corticosteroids or be maintaining the same dose level as baseline. Clinical 
symptoms must also be stable.  
Progressive Disease
Progressive disease (PD) will be defined by the occurrence of any of the following:  
!
The sum of the products of perpendicular diameters of enhancing lesions is increased 
by 25% or more compared with the smallest tumor measurement obtained either at 
baseline or the time point with the best response for patients receiving either stable or 
increasing doses of corticosteroids. 
!
There is a significant increase in T2/FLAIR non-enhancing lesions compared to 
baseline or best response scans for patients receiving either stable or increasing doses 
of corticosteroids. The increase in T2/FLAIR non-enhancing lesions should not be 
attributable to other non-tumor causes (e.g., radiation therapy, demyelination, 
ischemic injury, etc.). 
!
Appearance of new lesions. 
!
Clear progression of non-measurable lesions. 
!
There is clear clinical deterioration that is not attributable to other causes apart from 
the tumor (e.g., seizures, medication adverse effects, complications of therapy, 
cerebrovascular events, etc.) or changes in corticosteroid use. 
!
Failure to return for evaluation as a result of death or deteriorating condition. 
A summary of brain tumor response definitions (RANO) is shown in Table 15.

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Table 15:
Summary of RANO Response Criteria
Criterion
Complete 
Response
Partial 
Response
Stable Disease
Progressive 
Disease
T1 enhancing disease
None
≥ 50% ↓
< 50% ↓ but <25% ↑
≥ 25% ↑1
T2/FLAIR
Stable or ↓
Stable or ↓
Stable or ↓
↑1
New lesion
None
None
None
Present1
Corticosteroids
None
Stable or ↓
Stable or ↓
NA2
Clinical status
Stable or ↑
Stable or ↑
Stable or ↑
↓1
Requirement for response
All
All
All
Any1
Abbreviations: NA=not applicable, RANO = Response Assessment in Neuro-Oncology
1 Progression occurs when this criterion is present.
2 Increase in corticosteroids alone will not be taken into account in determining progression in the absence of 
persistent clinical deterioration.

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11.
REPORTING SAFETY INFORMATION
11.1.
Adverse Events/Serious Adverse Events
11.1.1.
Adverse Events
An AE is any untoward medical condition that occurs in a patient from the time the ICF is signed 
and does not necessarily have a causal relationship with the use of the product. 
A complete and specific clinical diagnosis should be provided for the AE verbatim term. If a 
diagnosis is not available, then signs and symptoms should be reported. The CTCAE (version 
4.03) terms are to be used to assess severity and provide the grade for each AE that is reported.
For definitions and reporting of pregnancy, overdose, and medication errors, refer to 
Section 11.1.5, Pregnancy, Section 11.1.6, Overdose, and Section 11.1.7, Medication Errors, 
respectively. 
Any untoward medical event that occurs outside the period of patient follow-up (30 days after 
the last dose of study drug or until the start of new antitumor therapy, (whichever is earlier) is 
not considered an AE.
Symptoms or laboratory or instrumental (e.g., electrocardiographic) abnormalities of a pre-
existing disease, such as cancer or other diseases, should not be considered an AE. However, 
occurrences of new symptoms as well as worsening of pre-existing medical conditions are 
considered AEs. In addition, a new laboratory or instrumental abnormality that has a 
clinical impact on a patient (e.g., resulting in study drug dose reduction, treatment delay, 
treatment discontinuation) is considered an AE, unless it is considered part of clinical 
manifestations to a clinical diagnosis that is already reported as an AE.
All AEs will be reported from the time the main study ICF is signed through the period of patient 
follow-up (30 days after the last dose of study drug or until the start of new antitumor therapy, 
whichever is earlier).  For the Phase 2 part of the study, any AEs that occur after the signing of 
pre-screening consent and are directly associated with a pre-screening procedure (i.e., fresh 
tumor biopsy) should be reported. For AEs that occur between signing the pre-screening consent 
and main study ICF, there is no need to record those that are unrelated unless it is mandatory by 
local regulations. All AEs will be documented in the eCRF. Documentation should include onset 
and resolution/stabilization dates, severity/grade, relationship to study drug, and outcome of the 
event. All AEs should be entered in the eCRF within 10 business days from the time the 
investigator first becomes aware of the AE. 
Causal relationship is assessed based on the following:
1. Select “Related” if the event follows a reasonable temporal sequence from administration 
of study medication and at least one of the following conditions is true:
!
A positive dechallenge: This means that the event improves or resolves after the drug 
is stopped (temporarily or permanently).
!
A positive rechallenge: This means that the event reappears after the drug is restarted.
!
The event cannot be reasonably explained by the patient’s clinical state and/or other 
therapies administered.

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The circumstance that a causal relationship can sometimes not be ruled out is not sufficient to 
determine that the event is “related”. Instead, “related” should mean that there is evidence to 
suggest a causal relationship between the drug and the AE. A reasonable possibility is provided 
by the following example that would suggest a causal relationship between drug and the event: A 
single occurrence of an event that is uncommon and known to be strongly associated with drug 
exposure (e.g., angioedema, Stevens-Johnson syndrome).
2. Select “Not related” if there is no reasonable possibility that the study medication caused 
the event, or if the event does not follow a reasonable temporal sequence from 
administration of study medication and could have been produced by a documented pre-
existing condition, concomitant medication or patient’s clinical state. For the purposes of 
safety reporting, “no reasonable possibility” means there is no evidence to suggest a 
causal relationship between the drug and the AE.
Any ongoing AEs should be followed until the earliest occurrence of one of the following:
!
AE has resolved.
!
AE has stabilized.
!
The AE reporting process is provided in the eCRF Completion Guidelines.
11.1.2.
Serious Adverse Events
An SAE is an AE that falls into one or more of the following categories:
a.
Results in death.
b. Is life threatening (e.g., an event that, in the view of the investigator, places the 
patient at immediate risk of death from the event as it occurred [it does not include an 
event, which hypothetically might have caused death if it were more severe]).
c.
Requires inpatient hospitalization or prolongation of existing hospitalization. The 
following are not considered hospitalizations for the purposes of assessing 
seriousness:
!
Emergency room visits < 24 hours.
!
Hospitalizations for preplanned procedures.
!
Hospitalization for study-related treatment and procedures.
d. Results in persistent or significant disability or incapacity, where disability is defined 
as a substantial disruption of a person’s ability to conduct normal life functions, either 
reported or defined as per clinical judgment.
e.
Is a congenital anomaly/birth defect (if exposure to product just before conception or 
during pregnancy resulted in an adverse outcome in the child).
f.
Is any other important medical event (e.g., may not result in death, be life-threatening, 
or require hospitalization), but based upon appropriate medical judgment, it may 
jeopardize the patient and may require medical or surgical intervention to prevent one 
of the outcomes listed in the points above. Examples of such events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, and 
blood dyscrasias or convulsions that do not result in inpatient hospitalization.

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Serious AEs must be reported to TOI Pharmacovigilance or designee within 24 hours from the 
time the investigator first becomes aware of the SAE by completing a Serious Adverse Event 
Form and faxing or emailing it to Taiho Pharmacovigilance or designee.  Comprehensive 
information available at the time of initial reporting (including narrative description, medical 
history, and concomitant medications) needs to be provided with careful consideration regarding 
causality and serious criterion. The SAE reporting process and contact information for reporting 
the SAE are provided on the SAE Form Completion Guidelines.
After the initial SAE reporting to TOI Pharmacovigilance or designee, follow-up SAE 
information will be submitted, by faxing or emailing an updated Serious Adverse Event Form, 
each time that important follow-up information (e.g., diagnosis, outcome, causality assessment, 
results of specific investigations) becomes available.
All SAEs within the follow-up window (e.g., within 30 days after the last dose of study drug or 
until the start of new antitumor therapy, whichever is earlier) established in the protocol will be 
reported to TOI Pharmacovigilance or designee.
If serious medical occurrences including deaths outside the follow-up window established by the 
protocol are reported to or observed by the investigator that he/she believes are related to the 
administration of TAS-120, it is the investigator’s responsibility to report this occurrence to TOI
Pharmacovigilance or designee.
11.1.3.
Reporting of Deaths
All deaths including death due to clinical disease progression occurring through the 30-day 
follow-up period must be reported as an SAE within 24 hours:
!
Death is not an acceptable AE/SAE term. Death is an outcome of an SAE.
When reporting a death, site personnel will be required to identify which of the following best 
describes the category of death:  
!
Toxicity caused by study drug.
!
Radiologic disease progression.
!
Clinical disease progression.
!
Other causes.
11.1.4.
Disease Progression 
How to report events related to nonfatal disease progression:
!
Disease progression is not an acceptable AE term. In cases of nonfatal disease 
progression, the relevant signs, symptoms and complications that led to the diagnosis 
of clinical disease progression should be reported as an AE. If the relevant signs, 
symptoms and complications meet any of the serious criteria, they should be reported 
as SAEs. In both cases it should be indicated whether the signs, symptoms and 
complications are related to clinical disease progression.
How to report events related to fatal disease progression:

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!
In cases of death due to clinical disease progression, the relevant signs, symptoms, 
and complications that led to the diagnosis of clinical disease progression should be 
reported as SAE terms. Clinical disease progression may only be reported as an SAE 
term if none of the relevant signs or symptoms supports a fatal outcome.
11.1.5.
Pregnancy
If a patient becomes pregnant while in the study, the study treatment must be immediately 
discontinued. Pregnancy information in a female patient or in the female partner of a male 
patient should be reported within 24 hours from the time the investigator first becomes aware of 
a pregnancy or its outcome. This should be performed by completing a Pregnancy Form and 
faxing or emailing it to TOI Pharmacovigilance or designee. 
New and/or corrected information regarding the pregnancy obtained after submitting the 
Pregnancy Form must be submitted by faxing an updated Pregnancy Form to TOI
Pharmacovigilance or designee.
If outcome of the pregnancy is a stillbirth, congenital anomaly/birth defect, or a serious event in 
the mother, report as an SAE to TOI Pharmacovigilance or designee.
11.1.6.
Overdose
An overdose with TAS-120 for this clinical trial is defined as taking a dose beyond the protocol-
defined dose (taking into account any dose reductions / re-escalations) in 1 day.
An overdose of TAS-120 must be reported to TOI Pharmacovigilance or designee within 24 
hours from the time the investigator first becomes aware of the overdose, whether or not it was 
accidental or intentional, and whether or not the patient developed an AE (even if not fulfilling a 
seriousness criterion). This should be performed by completing a Serious Adverse Event Report 
Form and faxing or emailing it to TOI Pharmacovigilance or designee).  
An accidental or intentional overdose of concomitant medication should only be reported if it is 
associated with an AE.
There is no known antidote available in case of TAS-120 overdose. Overdose should be 
managed aggressively with close monitoring and administration of prophylactic and 
symptomatic therapies to prevent or correct potential side effects. 
11.1.7.
Medication Errors
A medication error for this clinical trial is defined as an accidental, incorrect administration of a 
medicinal product. The error can be related to the administration of a wrong medication, nature 
of the medication, route of administration, dosage, or frequency of the treatment (including 
omission of one or more administrations).
The following types of medication errors, whether or not they meet the serious criteria, should be 
reported to TOI Pharmacovigilance Operations within 24 hours of first awareness, by 
completing the Serious Adverse Event Report Form and faxing or emailing it to TOI 
Pharmacovigilance or designee.
!
Medication errors with study medication or concomitant medication resulting in an 
AE

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!
Medication errors with study medication resulting in an overdose
!
Incorrect route of study medication administration
!
Administration of the incorrect study medication
**Medication errors with the study medication that result in the omission of an administration, 
an incorrect dose, or the administration of more than the prescribed dose (but does not meet the 
overdose criteria), will not be reported as an SAE, but will be identified through the recording of 
study drug accountability data in the eCRF.
11.1.8.
Breaking the Study Blind
This is an open-label study.
11.2.
Laboratory Evaluations
11.2.1.
Reporting and Evaluation of Laboratory Test Results
Laboratory tests will be performed as required per protocol. All laboratory values that are out of 
the normal range will be evaluated for their clinical significance before exposing the patient to 
the next dose of TAS-120.  
The laboratory must provide normal reference ranges.  
Any laboratory abnormality that has a clinical impact on the patient (e.g., results in delay of 
TAS-120 dosing, study discontinuation) must be reported as an AE, unless it is considered a 
supporting lab to a clinical diagnosis that is already reported as an AE. Febrile neutropenia must 
be reported as an AE and is defined as an ANC < 1 000/mm3 with a single body temperature of > 
38.3°C (101°F) or a sustained temperature of ≥38°C (100.4°F) for more than 1 hour. All 
laboratory data will be analyzed using NCI CTCAE grade criteria (version 4.03).
11.2.2.
Repeat Testing
Evaluation of any clinically significant laboratory test will be repeated, as clinically indicated, 
until the value returns to the baseline level or clinically stabilizes, or until new anticancer 
treatment, surgery, or radiotherapy is given.
11.3.
Physical Examination and Performance Status
Physical examinations and performance status evaluations will be performed as described in the 
Study Procedures section of the protocol. If changes are observed, the investigator will determine 
whether they meet the definition of an AE. All observations and evaluations will be documented.
11.4.
Vital Signs and Body Weight
Vital signs and body weight will be verified and documented. If a clinically significant change is 
observed, the measurement will be repeated as clinically indicated and evaluated for its clinical 
relevance and whether it meets the definition of an AE.

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12.
STATISTICS
This section outlines the statistical methodology to be used to summarize the study results. A 
SAP will be prepared as a separate document. The SAP will include a more technical and 
detailed description of the planned statistical summaries and will be finalized prior to closing of 
the database.
12.1.
Study Populations
The study populations include safety, DLT-evaluable, PK, pharmacodynamic, and efficacy 
populations.
Safety Population
The safety population will include all patients who received at least 1 dose of TAS-120. This 
population will be the primary population for safety evaluation. 
DLT Evaluable Population (Phase 1 Dose Escalation only)
The DLT evaluable population was defined for Phase 1 Dose Escalation only; Phase 1 Dose 
Escalation has been completed as of Amendment 6.  
PK and Pharmacodynamic Population
The PK and pharmacodynamic population will consist of all patients who received TAS-120 and 
have TAS-120 evaluable plasma and/or urine data. All such patients will be evaluated for PK and 
pharmacodynamics unless significant protocol deviations have impacted the data or key dosing 
information is missing. Changes to the procedures, which may impact the quality of PK and 
pharmacodynamic data, will be considered “PK and pharmacodynamics relevant protocol 
deviations.” Examples include sample processing errors that lead to inaccurate bioanalytical 
results and/or inaccurate dosing on the day of PK and pharmacodynamic sampling.
Efficacy Population
The efficacy population is defined for each portion of the study as follows:
!
Phase 1 Dose Escalation:  All treated patients (safety population)
!
Phase 1 Expansion: All treated patients (safety population)
!
Phase 2: All treated iCCA patients with confirmed FGFR2 gene fusions
12.2.
Statistical Analysis
12.2.1.
Patient Disposition, Baseline and Treatment Characteristics
12.2.1.1.
Patient Disposition
The number of patients in each study population and the reasons for exclusion will be 
summarized. In addition, patients’ status with regard to study treatment and follow-up will also 
be summarized, along with the reasons for study discontinuation.

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12.2.1.2.
Patient Baseline Characteristics
Patient disease and baseline characteristics will be summarized using frequency distribution or 
descriptive statistics as appropriate.
12.2.1.3.
Study Treatment
The TAS-120 administration profile will be summarized with respect to number of cycles taken, 
the dose intensity, dose modifications, and reasons for deviations from the planned regimen.
12.2.2.
Efficacy Analysis
Tumor assessments will be performed as per Section 9.17, Tumor Assessments/Scans. For the 
Phase 1 Expansion, the primary endpoint is ORR (and EPR for primary CNS tumors), and 
secondary endpoints are DCR, DOR, PFS, OS. 
For Phase 2, the primary endpoint is ORR and the secondary endpoints are DOR, DCR, PFS, 
PROs and OS (response evaluations based on independent review of images by the Core Imaging 
Laboratory).  In addition, sensitivity analyses for some key efficacy endpoints (notably ORR and 
PFS) will be performed based on assessments by the investigator or local radiologist.  
Response assessments will be made based on RECIST guidelines (version 1.1, 2009) for solid 
tumors (see Section 10.1, Efficacy Assessment for Solid Tumors) or RANO for brain tumors (see 
Section 10.2).
12.2.2.1.
Objective Response Rate
Objective response rate (ORR) is defined as the proportion of patients with objective evidence of 
CR or PR. The evaluation of ORR will be based on investigator assessment and/or central
independent review of the images as follows:
!
Phase 1 dose escalation: Local CT/MRI assessment and collect CT scans or MRI for 
future central independent review, if warranted.
!
Phase 1 expansion: Local CT/MRI assessment and collect CT scans or MRI for future 
central independent review, if warranted.
!
Phase 2: Central independent CT/MRI image assessments (primary analysis) and 
local CT/MRI image assessments (sensitivity analysis).  
At the analysis stage, the best objective response will be assigned for each patient as the best 
response recorded after initiation of study treatment and confirmed at least 4 weeks later. If 
applicable, responses recorded after disease progression or initiation of new anticancer treatment 
will be excluded. 
The exact 2-sided CI based on Clopper-Pearson methodology will be derived for ORR.
12.2.2.2.
Disease Control Rate
The assessment of DCR will parallel that of ORR, with DCR defined as the proportion of 
patients with objective evidence of CR, PR, or SD, except that there is no requirement for a 
confirmation of an SD response, if it is maintained for at least 6 weeks post treatment initiation.
Disease control rate will be analyzed using the same methodology as ORR.  

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12.2.2.3.
Duration of Response
Duration of response (DOR) is derived for those patients with objective evidence of PR or CR. 
Duration of response is defined as the time from the first documentation of response (CR or PR) 
to the first documentation of objective tumor progression or death due to any cause, whichever 
occurs first. Patients who are alive and progression-free as of the analysis cut-off date will be 
censored at their last evaluable tumor response assessment prior to initiation of any new 
anticancer cancer treatment. Patients who start subsequent anticancer therapy without a prior 
reported progression will be censored at the last tumor assessments prior to initiation of the 
subsequent anticancer therapy. This endpoint will only be evaluated in patients with objective 
response of CR or PR.
Duration of response will be analyzed as a time-to-event endpoint with the median (Kaplan-
Meier estimate) and associated 95% CI (Brookmeyer-Crowley methodology) reported.
12.2.2.4.
Progression-free Survival
Progression-free survival (PFS) is defined as the time from the day of the first dose to the date of 
first objectively documented disease progression or death (any cause), whichever occurs first. 
Patients who die without a reported disease progression will be considered to have progressed on 
the date of their death.  Patients who did not progress or die will be censored on the date of their 
last tumor assessment. Patients who did not have any on-study assessments and did not die will 
be censored on the first dosing date. Patients who started any subsequent anti-cancer therapy 
without a prior reported progression will be censored at the last tumor assessment prior to 
initiation of the subsequent anti-cancer therapy. Early progression rate (EPR) for the GBM or 
Grade III glioma cohort will be assessed as the progression-free rate at the end of Cycle 2.
Progression-free survival will also be analyzed as a time-to-event endpoint with the median 
(Kaplan-Meier estimate) and associated 95% CI (Brookmeyer-Crowley methodology) reported, 
along with the Kaplan-Meier estimates for PFS rates at 3, 6, 9 and 12 months and associated 
95% CIs (log-log transformation methodology of Kalbfleisch-Prentice). 
12.2.2.5.
Overall Survival
Overall survival (OS) is defined as the time (in months) from the date of the first dose to the 
death date, in the safety population for the Phase 1 Dose Escalation and Phase 1 Expansion parts 
of the study and the efficacy population for the Phase 2 part of the study.  In the absence of death 
confirmation or for patients alive as of the OS cut-off date, survival time will be censored at the 
date of last study follow-up, or the cut-off date, whichever is earlier.
Overall survival will be analyzed similar to PFS.
12.2.2.6.
Patient-Reported Outcomes
The analyses of EQ-5D and EORTC QLQ-C30 will be performed in all treated patients who 
have an assessment at baseline and at least one subsequent assessment.

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EQ-5D
Patient’s overall health state on a visual analog scale (EQ-VAS) at each assessment time point 
will be summarized using descriptive statistics. Proportion of patient’s reporting problems for the 
5 EQ-5D dimensions at each assessment time point will be summarized by level of problem. 
Percentages will be based on number patients assessed at each assessment time point.
A by-patient listing of EQ-5D with the problem levels for each of the 5 dimensions (mobility, 
self-care, usual activities, pain/discomfort and anxiety/depression), health state (5 dimensions 
digits combined in a 5-digit number) and EQ-VAS will be provided.
EORTC QLQ-C30
All scales and single items are scored on a categorical scale and linearly transformed to 0-to-100 
scales with higher scores for a functional scale representing higher levels of functioning, higher 
scores for the global health status/quality of life representing higher levels of global health 
status/quality of life, and higher scores for a symptom scale representing higher level of 
symptoms.
Baseline and change from baseline in EORTC QLQ-C30 global health status/quality of life 
(QoL) composite scale data and the remaining EORTC QLQ-C30 scale data will be summarized 
by time point using descriptive statistics for each cohort. In addition, the percentage of patients 
demonstrating a clinically meaningful deterioration (defined as a 10-point change from baseline) 
will be presented for each scale at each assessment time point. Percentages will be based on 
number patients assessed at each assessment time point.
12.2.3.
Safety
The safety evaluations will focus on the AEs and laboratory assessments. All patients included in 
the safety population will be evaluated in the safety analysis.
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA) terminology and the severity of the toxicities will be graded according to the NCI 
CTCAE (version 4.03) where applicable. Concomitant medications will be coded according to 
World Health Organization (WHO) Drug Dictionary for Concomitant Medication.
All AEs will be summarized (incidence) and listed by the System Organ Class (SOC), preferred 
term (PT), toxicity/severity grade, and causal relationship to TAS-120. In addition, separate 
summaries of SAEs and Grade 3 or 4 AEs will be presented.
Hematological and chemistry laboratory parameters will be graded according to the NCI CTCAE 
(version 4.03) where applicable. The worst severity grade, time to maximum Grade 3 or 4 value, 
and time to resolution (return to baseline grade or below) will be summarized. 
12.2.4.
Pharmacokinetic Analysis
For Phase 1, the PK parameters in plasma and urine will be calculated by standard 
noncompartmental methods. In addition, the accumulation ratio will be also calculated for the 
last Wednesday of Cycle 1 (QOD arm) or Day 21 (QD arm) after repeated administrations, as 
applicable. Dose-proportionality of TAS-120 will be evaluated based on linear, power regression 
analyses, and 1-way analysis of variance. The detailed analytical method will be specified in the 

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Statistical Analysis Protocol. When further exploratory analyses are performed, the methods and 
the results may be reported in the Pharmacokinetic Analysis Report prepared separately.
!
Cmax
Maximum concentration in plasma
!
Tmax
Time to reach maximum concentration in plasma
!
AUC0-24
Area under the concentration-time curve up to 24 hours (QD arm)
!
AUC0-48
Area under the concentration-time curve up to 48 hours (QOD arm)
!
AUC0-last
Area under the concentration-time curve up to the last observable 
concentration
!
AUC0-inf
Area under the concentration-time curve up to infinity
!
T1/2
Elimination half-life time
The following parameters will be calculated only on Day 1.
!
MRT
Mean residence time 
!
CL/F
Oral clearance
!
Vd/F
Volume of distribution
!
Ae%
Urinary excretion rate as % of dose (QOD arm)
!
CLr
Renal clearance (QOD arm)
The PK parameters will be calculated by noncompartmental method or population PK analysis 
method using Phoenix® WinNonlin (version 6.1 or later, Pharsight Corporation) or NONMEM®
(version 7.2 or later, ICON Development Solutions).
In addition, the TAS-120 concentration ratio of CSF to plasma will be calculated.
12.2.5.
Pharmacodynamic Analysis (Phase 1 Dose Escalation only) 
Pharmacodynamic data (FGF23 and phosphorus in serum, and phosphorus and calcium in urine) 
for individual time data will be summarized descriptively by dose level and schedule. Where 
possible, relationship between plasma PK parameters or concentration of TAS-120 will be 
evaluated by correlation analysis or visual inspections. When further exploratory analyses are 
performed, the methods and the results may be reported in the Pharmacodynamic Analysis 
Report. 
CCI

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CCI

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CCI

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13.
ETHICS
13.1.
Ethical Considerations
It is mandatory that all considerations regarding the protection of human subjects be carried out 
in accordance with the protocol, Good Clinical Practice (GCP), ICH Guidelines, the ethical 
principles that have their origin in the Declaration of Helsinki, and all applicable regulatory 
requirements.
13.2.
Informed Consent and Patient Information
Obtaining informed consent must be done according to the guidelines provided in the 
Declaration of Helsinki, ICH E6 Guideline for GCP, and local regulations.
The investigator (according to applicable regulatory requirements) or a person designated by the 
investigator and under the investigator’s responsibility should fully inform patients of all 
pertinent aspects of the clinical trial. All participants should be informed to the fullest extent 
possible about the study in a language and in terms they are able to understand.
Prior to participation in the trial, the written ICF is to be signed and personally dated by the 
patient or by the patient’s legal representative and by the person who conducted the ICF 
discussion. A copy of the signed and dated ICF will be provided to the patient. The ICF used 
must have had prior approval by the Institutional Review Board (IRB)/Independent Ethics 
Committee (IEC).
13.3.
Institutional Review Board/Independent Ethics Committee Approval
The study must be approved by an appropriately constituted IRB/IEC, as required in Chapter 3 of 
the ICH E6 Guidelines, applicable local regulations, and, for studies conducted under an 
Investigational New Drug (IND) application, the United States of America (USA) Code of 
Federal Regulations (CFR) Title 21 Part 56.
The IRB/IEC must provide written approval of the study. The written approval/favorable opinion 
should include protocol (title, number and version number), list of documents reviewed (e.g., 
protocol, ICF, IB, curriculum vitae), and the date of the review.
The investigator is required to submit a copy of the written and dated IRB/IEC 
approval/favorable opinion to the sponsor or its representative prior to initiation of this study.
Investigational product will not be released to the trial site and the investigator will not start the 
trial until this written IRB/IEC approval/favorable opinion is received by the sponsor or its 
representative.
The investigator is responsible for obtaining renewal of approval throughout the duration of the 
study. Timeframes for renewal will be based on IRB/IEC requirements but renewal at least 
annually is required by regulations.  
At the end of the trial, the IRB/IEC will be notified of the conclusion of the trial and its outcome.

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13.4.
Post-study Provisions
After the completion of the study, if a patient still requires administration of study drug which 
has been assessed as beneficial per the investigator, the Sponsor and investigator will discuss the 
post-study provisions for the patient’s access to study drug. At that time, patients will follow the 
procedures described in the Study Schedules for the EOT Visit and Safety Follow-up procedures. 
Subsequently, with the exception of SAEs and treatment-related AEs, data will not be collected 
in the electronic data capture (EDC) system. 

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14.
ADMINISTRATIVE CONSIDERATIONS
14.1.
Protocol Amendments
No change to the protocol may be made without the joint agreement of both the investigator and 
sponsor. Any amendment to the original protocol will be made by sponsor and will be signed by 
both parties and submitted to the IRB/IEC and appropriate regulatory authorities for approval or 
notification.
14.2.
Curriculum Vitae
All investigators and any subinvestigator(s) must provide sponsor with current (within 2 years) 
signed and dated copies of their own curriculum vitae listing the experience, qualifications, and 
training prior to the beginning of the study.
14.3.
Administrative Structure
The administrative structure of the study (e.g., CROs) will be provided to all sites.  
In addition to ongoing safety monitoring during the study, a more comprehensive evaluation of 
the ongoing study safety profile will take place when key study milestones are met, such as 
completion of the DLT period in a specific cohort. At the end of each DLT period, the sponsor 
will review and discuss specific DLTs with the corresponding investigators, and the selection or 
rejection of particular doses as MTDs will be communicated directly to all active investigators.  
14.4.
Monitoring Procedures
14.4.1.
Investigator’s Responsibilities
The investigator agrees to conduct the study in accordance with the Clinical Trial Protocol, ICH 
guidelines E6 – GCP, Section 4 – investigator’s obligations and the applicable regulatory 
requirements.
The investigator is required to ensure compliance with the protocol and other procedures 
provided by the sponsor. The investigator agrees to provide reliable data and all information 
required by the protocol, eCRF, SAE forms, and Data Resolution Forms or any other appropriate 
instrument. This information must be accurate, legible, and according to instructions provided.
The investigator must ensure that the sponsor, sponsor’s representatives, and regulatory agencies 
will have access to such documentation.
The investigator may appoint subinvestigators to assist in the conduct of the trial. All 
subinvestigators shall be appointed and listed in a timely manner. They will be supervised and 
work under the responsibility of the investigator.
14.4.2.
Sponsor’s Responsibilities
The sponsor is responsible to health authorities for taking all reasonable steps to ensure the 
proper conduct of the clinical trial protocol with regard to ethics, protocol compliance, and 
integrity and validity of the data recorded in the eCRFs. Thus, the main duty of the monitor is to 

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help the investigator and the sponsor maintain a high level of ethical, scientific, technical, 
regulatory, and quality in all aspects of the trial.
At regular intervals during the trial, the site will be contacted, through monitoring visits, letters 
or telephone calls by the sponsor or its representatives to review study progress, investigator and 
patient’s compliance with requirements, and follow up on any issues to be addressed. During the 
monitoring visits, source documents, informed consent, recruitment, SAE documentation and 
reporting, investigational product accountability, concomitant medications, AEs, eCRFs, and 
queries will be reviewed with the investigator.
14.4.3.
Source Documents
According to ICH guidelines the monitor will check the eCRF entries against the source 
documents. Source documents are original documents, data, and records (e.g., hospital records, 
clinical and office charts, laboratory notes, memoranda, patient’s evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions 
certified after verification as being accurate and complete, microfiches, photographic negatives, 
microfilm or magnetic media, x-rays, patient files, and records kept at the pharmacy, at 
laboratories, and at medical-technical departments involved in the clinical trial).
The Informed Consent will include a statement by which the patient allows the sponsor’s duly 
authorized personnel, the IRB/IEC, and regulatory authorities to have direct access to original 
records supporting eCRF data.
14.4.4.
Case Report Form
Investigators will be provided with detailed eCRF Completion Guidelines that will identify the 
required data points to be collected, how to document them, and when the data should be 
documented.
It is the responsibility of the investigator to maintain adequate and accurate eCRFs to record 
(according to the eCRF Completion Guidelines) all observations and other data pertinent to the 
clinical trial obtained during scheduled or unscheduled visits. All eCRFs should be fully 
completed to ensure accurate data interpretation.
The computerized handling of the data by the sponsor after receipt of the eCRFs may generate 
additional requests via paper queries or other means to which the investigator is obliged to 
respond by confirming or modifying the data questioned. These requests with their responses 
will be appended to the eCRFs held by the investigator and sponsor.
14.4.5.
Sponsor’s Audits and Regulatory Inspections
For the purpose of ensuring compliance with the protocol, GCP and applicable regulatory 
requirements, the investigator will permit auditing by the sponsor or its representative and 
inspections by regulatory authorities.
The investigator agrees to allow the auditors and inspectors to have direct access to the study 
records for review. The people performing these activities will not disclose any personal identity 
or personal medical information assessed.

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The investigator will make every effort to help with the performance of the audits and 
inspections, giving access to all necessary facilities, data and documents pertaining to the clinical 
trial. As soon as the investigator is notified of a planned inspection by the regulatory authorities 
or IRB/IEC, the investigator will inform the sponsor. Any results arising from such inspections 
will be immediately communicated by the investigator to the sponsor. The investigator shall take 
appropriate measures required by the sponsor to take corrective actions for all problems found 
during audits and/or inspections.
14.5.
Archiving of Records
The investigator is responsible for the retention of all study documents according to institutional 
policies, local laws, ICH Parts 4.9.4 and 4.9.5 and, for studies conducted under an IND 
application, the USA CFR Title 21 Part 312.62. For more information on USA requirements and 
ICH Guidelines, please go to www.fda.gov and www.ema.europa.eu.
The investigator agrees to inform sponsor in writing of the intention to remove or destroy any 
study-related records. Prior to contacting sponsor, the investigator must ensure that institutional 
and local requirements (for example, ICH Guidelines) have been satisfied. Taiho Oncology, Inc. 
Regulatory Affairs will evaluate the investigator’s request. The sponsor will provide 
authorization for destruction of such records to the investigator in writing.
In the event that all retention of records requirements have been fulfilled, but sponsor requests 
that the investigator maintain the records for a longer period of time, additional arrangements 
will be made.
14.6.
Final Report
Whether the study is completed or prematurely terminated, a final report of the study will be 
written by the sponsor or its designee and submitted to the regulatory agency(ies), as required by 
the applicable regulations.
The final study report will be retained by the sponsor, or by any other subsequent owner of this 
drug, for 5 years beyond the lifetime of the product.
14.7.
Use and Publication of Study Results
All unpublished documentation (including the protocol, eCRF, and IB) given to the investigator 
is strictly confidential. All recipients must agree not to disclose the information contained herein 
to any person without the prior written authorization of the sponsor. The submission of these 
documents to the IRB/IEC is permitted. The investigator agrees that the sponsor maintains the 
right to use the results of this study in their original form and/or in a global report for submission 
to governmental and regulatory authorities of any country.
The results of the study may be presented during scientific symposia or published in a scientific 
journal only after review by the sponsor in accordance with the guidelines set forth in the 
applicable publication or financial agreement.

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14.8.
Financial Disclosure
Financial disclosure for clinical investigators and record keeping of financial records will be in 
accordance with local regulatory requirements.
14.9.
Termination of the Study
In the event that the investigator is unable to continue the study and another suitable person is 
designated as the investigator, the sponsor must be notified in advance (30 days prior to notice). 
The new investigator must accept the responsibility in writing and be approved by the sponsor 
and the IRB/IEC.
If the sponsor and/or the investigator should discover conditions arising during the study that 
indicate it should be terminated, an appropriate schedule for termination will be instituted. The 
sponsor also reserves the right to discontinue this study for administrative reasons at any time. 
The investigator will be reimbursed for reasonable expenses incurred, if it is necessary to 
terminate the study or an individual patient's participation. The sponsor will not reimburse the 
investigator for the evaluation of patients if the evaluations are not conducted in compliance with 
the final protocol.
A supplemental Pharmaceuticals and Medical Devices Agency (PMDA) appendix (for Japan 
only) is provided in Appendix G.

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15.
CONFIDENTIALITY AND DATA PROTECTION
All information provided to the investigator by the sponsor or sponsor’s representatives, 
information produced during the clinical trial including, but not limited to, the protocol, eCRF, 
IB, and the results obtained during the course of the trial are confidential. The members of the 
research team agree not to discuss such information in any way without prior written permission 
from the sponsor.
However, the submission of the protocol and necessary documentation to the IRB/IEC is 
permitted. The IRB/IEC members have the same obligation of confidentiality.
The patient’s personal data and investigator’s personal data which may be included in the 
sponsor’s database shall be treated in compliance with all applicable laws and regulations.
When processing and archiving personal data pertaining to the investigator and or to the patients, 
the sponsor or its representatives shall take all appropriate measures to safeguard and prevent 
access to this data by any unauthorized third party.

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17.
REFERENCES
1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000 Jan 7;100:57-70.
2. Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor 
receptors. Cytokine Growth Factor Rev. 2005 Apr;16(2):139-49.
3. Fukumoto S. Actions and mode of actions of FGF19 subfamily members. Endocr J. 2008 
Mar;55:23-31.
4. Brooks AN, Kilgour E, Smith PD. Molecular pathways: fibroblast growth factor signaling: a 
new therapeutic opportunity in cancer. Clin Cancer Res. 2012 Apr 1;18(7):1855-62.
5. Courjal F, Cuny M, Simony-Lafontaine J, et al. Mapping of DNA amplifications at 
15 chromosomal localizations in 1875 breast tumors: definition of phenotypic groups. 
Cancer Res. 1997 Oct 1;57(19):4360-7.
6. Kim HR, Kim DJ, Kang DR, et al. Fibroblast growth factor receptor 1 gene amplification is 
associated with poor survival and cigarette smoking dosage in patients with resected 
squamous cell lung cancer. J Clin Oncol. 2013 Feb 20;31(6):731-7.
7. Toyokawa T, Yashiro M, Hirakawa K. Co-expression of keratinocyte growth factor and K-
sam is an independent prognostic factor in gastric carcinoma. Oncol Rep. 2009 
Apr;21(4):875-80.
8. Nord H, Segersten U, Sandgren J, et al. Focal amplifications are associated with high grade 
and recurrences in stage Ta bladder carcinoma. Int J Cancer. 2010 Mar 15;126(6):1390-402.
9. Kalff A, Spencer A. The t(4;14) translocation and FGFR3 overexpression in multiple 
myeloma: prognostic implications and current clinical strategies. Blood Cancer J. 2012 Sep 
7;2, e89.
10. Ang C.  Role of the fibroblast growth factor receptor axis in cholangiocarcinoma.  Journal of 
Gastroenterology and Hepatology. 2015;30:1116-1122.
11. Borad, M. J., Gores, G. J., & Roberts, L. R. (2015). Fibroblast growth factor receptor 2 
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12. Goyal L, Saha S, Liu L, et al. Polyclonal Secondary FGFR2 Mutations Drive Acquired 
Resistance to FGFR Inhibition in Patients with FGFR2 Fusion-Positive 
Cholangiocarcinoma. Cancer Discov. 2017;7(3)252-263.
13. Lamarca A, Hubner RA, Ryder WD, et al.  Second-line chemotherapy in advanced biliary 
cancer:  a systematic review.  Annals of Oncology.  2014;25:2328-2338.
14. Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for 
biliary tract cancer. NEJM. 2010;362:1273-1281.
15. Benson AB, Ajani JA, Catalano RB, et al. Recommended guidelines for the treatment of 
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18. Barker FG, 2nd, Chang SM, Gutin PH, et al. Survival and functional status after resection of 
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FGFR inhibition in a translational clinical trial. Cancer Discov. 2016;6: 838-51.
23. Meric-Bernstam F, Arkenau H, Tran B, Bahleda R, Kelley R, Hierro C.  Efficacy of 
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with chemotherapy and other FGFR inhibitors.  Ann Oncol.  2019;29(suppl_5):O-001.

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APPENDIX E. DIETARY GUIDELINES FOR TREATMENT OF 
HYPERPHOSPHATEMIA
The best way to limit phosphorus in the diet is to limit foods highest in phosphorus, including:
!
Fast food, convenience foods and processed foods, which may be full of phosphorus additives
!
Beverages that contain phosphorus (look for the letters "phos" in the ingredient list)
Also, look for any ingredient that contains "phos" in the term such as:
!
Calcium phosphate
!
Disodium phosphate 
!
Phosphoric acid
!
Monopotassium phosphate
!
Sodium acid pyrophosphate
!
Sodium tripolyphosphate
Listing of Some Lower and Higher Phosphorus Foods
Higher Phosphorus Foods
Lower Phosphorus Foods
Milk, pudding, yogurt, soy milk, nondairy creamers and 
enriched rice milk
Unenriched rice milk
Processed cheeses and cheese spreads
A small amount of Brie or Swiss cheese
Hard cheeses, ricotta or cottage cheese, fat-free cream 
cheese
Regular or low-fat cream cheese
Ice cream or frozen yogurt
Sherbet, sorbet or frozen fruit pops
Soups made with higher phosphorus ingredients (milk, 
dried peas, beans, lentils)
Soups made with lower phosphorus ingredients 
(broth- or water-based with other lower phosphorus 
ingredients)
Whole grains, including whole-grain breads, crackers, 
cereal, rice and pasta
White bread, crackers, cereals, rice and pasta
Quick breads, biscuits, cornbread, muffins, pancakes or 
waffles
White dinner rolls, bread, bagels or English muffins
Dried peas (split, black-eyed), beans (black, garbanzo, 
lima, kidney, navy, pinto) or lentils 
Green peas, green beans or wax beans
Processed meats, such as bologna, ham and hot dogs, and 
meat, poultry or seafood with "phos" in the ingredients
All-natural lean beef, pork, lamb, poultry, seafood or 
other fish without "phos" in the ingredients
Organ meats, walleye, pollock or sardines
All-natural lean beef, pork, lamb, poultry, seafood or 
other fish without "phos" in the ingredients
Nuts and seeds
Popcorn or pretzels
Peanut butter and other nut butters
Jam, jelly or honey
Chocolate, including chocolate drinks
Jelly beans, hard candy, fruit snacks or gumdrops
Colas and pepper-type sodas, some flavored waters, 
bottled teas, some drink mixes (any with "phos" in the 
ingredients)
Lemon-lime soda, ginger ale, root beer, plain water 
or some drink mixes (any without "phos" in the 
ingredients)
Although a food or drink may be low in phosphorus, limitation of portion size and the number of servings you eat 
or drink each day may still be recommended.
From: Rachael Majorowicz, R.D.N., L.D. (Feb, 2016). Why is a low-phosphorus diet useful in managing kidney disease? 
What foods contain phosphorus? https://www.mayoclinic.org/food-and-nutrition/expert-answers/faq-20058408.

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APPENDIX F.
CLASSIFICATION OF SUBSTRATES, INHIBITORS, AND 
INDUCERS OF CYP ENZYMES AND TRANSPORTERS
The classification below is based on the FDA Draft Guidance for Industry, Clinical Drug 
Interaction Studies —Study Design, Data Analysis, and Clinical Implications, October 2017. 
(http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/
UCM292362.pdf)
CYP3A inhibitors and inducers: CYP3A is involved in the metabolism of TAS-120. CYP3A 
inhibitors and inducers may alter the concentration and activity of TAS-120.
CYP3A substrates: TAS-120 is a potential time-dependent inhibitor of CYP3A. TAS-120 may 
increase the concentration and activity of CYP3A substrates.
P-gp substrates and BCRP substrates: TAS-120 is a potential inhibitor of P-gp and BCRP. TAS-
120 may alter the PK and activity of P-gp and BCRP substrates.
P-gp inhibitors and BCRP inhibitors: TAS-120 is a substrate of P-gp and BCRP. P-gp and BCRP 
inhibitors may alter the concentration and activity of TAS-120.
Examples of CYP3A Inhibitors
CYP Enzyme
Strong Inhibitors:1 ≥ 5-fold increase in AUC 
or ≥ 80% decrease in CL
Moderate Inhibitors:2 ≥2 but < 5-fold 
increase in AUC or 50 – 80% decrease 
in CL
CYP3A
Boceprevir, clarithromycin, cobicistat, 
conivaptan, danoprevir and ritonavir, diltiazem, 
elvitegravir and ritonavir, grapefruit juice,3
indinavir and ritonavir, idelalisib, itraconazole, 
ketoconazole, lopinavir and ritonavir, 
nefazodone, nelfinavir, paritaprevir and 
ritonavir and (ombitasvir and/or dasabuvir), 
posaconazole, ritonavir, saquinavir and 
ritonavir, telaprevir, tipranavir and ritonavir, 
troleandomycin, voriconazole
Aprepitant, cimetidine, ciprofloxacin, 
clotrimazole, crizotinib, cyclosporine, 
dronedarone, erythromycin, fluconazole, 
fluvoxamine, imatinib, tofisopam, 
verapamil
1 A strong inhibitor for a specific CYP is defined as an inhibitor that increases the area under concentration-time 
curve (AUC) of a substrate for that CYP by equal to or more than 5-fold.
2 A moderate inhibitor for a specific CYP is defined as an inhibitor that increases the AUC of a sensitive substrate 
for that CYP by less than 5-fold but equal to more than 2-fold.
3 The effect of grapefruit juice varies widely among brands and is concentration-, dose-, and 
preparationdependent. Studies have shown that it can be classified as a "strong CYP3A inhibitor" when a certain 
preparation was used (eg, high dose, double strength) or as a "moderate CYP3A inhibitor" when another 
preparation was used (eg, low dose, single strength).
Abbreviations: AUC = area under the concentration-time curve; CL = oral clearance.

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Example of CYP3A Inducers
CYP Enzyme
Strong inducersa or ≥ 80% decrease in 
AUC
Moderate Inducersb 50 – 80% decrease 
in AUC
CYP3A
Carbamazepine, enzalutamide, mitotane, 
phenytoin, rifampin, St. John’s wortc
Bosentan, efavirenz, etravirine, modafinil
a.
A strong inducer is a drug that decreases the AUC of sensitive index substrates of a given metabolic 
pathway by ≥80%.
b.
A moderate inducer is a drug that decreases the AUC of sensitive index substrates of a given metabolic 
pathway by ≥50% to <80%.
c.
The effect of St. John's wort varied widely and is preparation-dependent. 
Abbreviation: AUC = area under the concentration-time curve.
Example of CYP3A Substrates
CYP Enzymes
Sensitive Substratesa
Moderate Sensitive Substratesb
CYP3A
Alfentanil, avanafil, budesonide, buspirone, 
conivaptan, darifenacin, darunavir, dasatinib, 
dronedarone, ebastine, eletriptan, eplerenone, 
everolimus, felodipine, ibrutinib, indinavir, 
lomitapide, lovastatin, lurasidone, maraviroc, 
midazolam, naloxegol, nisoldipine, 
quetiapine, saquinavir, sildenafil, simvastatin, 
sirolimus, tacrolimus, ticagrelor, tipranavir, 
tolvaptan, triazolam, vardenafil
Alprazolam, aprepitant, atorvastatin, 
colchicine, eliglustat, pimozide, 
rilpivirine, rivaroxaban, tadalafil
a.
Sensitive substrates are drugs that demonstrate an increase in area under the concentration-time curve 
(AUC) of ≥5-fold with strong index inhibitors of a given metabolic pathway in clinical drug-drug 
interaction studies.
b
Moderate sensitive substrates are drugs that demonstrate an increase in AUC of ≥2 to < 5fold with strong 
index inhibitors of a given metabolic pathway in clinical drug-drug interaction studies.
Example of Inhibitors for P-gp and BCRP
Transporters
Gene
Inhibitor
P-gpa
ABCB1
Amiodarone, carvedilol, clarithromycin, dronedarone, itraconazole, 
lapatinib, lopinavir and ritonavir, propafenone, quinidine, ranolazine, 
ritonavir, saquinavir and ritonavir, telaprevir, tipranavir and ritonavir, 
verapamil
BCRPb
ABCG2
Curcumin, cyclosporine A, eltrombopag
a.
P-gp: (1) AUC fold-increase of digoxin ≥2 with co-administration and (2) in vitro inhibitor.
b.
BCRP: (1) AUC fold-increase of sulfasalazine ≥1.5 with co-administration and (2) in vitro inhibitor. 
Cyclosporine A and eltrombopag were also included, although the available DDI information was with 
rosuvastatin, where inhibition of both BCRP and OATPs may have contributed to the observed interaction.
Abbreviations: AUC = area under the concentration-time curve; BCRP = breast cancer resistance protein; P-gp = p-
glycoprotein.

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Example of Substrates for P-gp and BCRP
Transporters
Gene
Substrate
P-gpa
ABCB1
Dabigatran, digoxin, fexofenadine
BCRPb
ABCG2
Rosuvastatin, sulfasalazine
a.
P-gp: (1) AUC fold-increase≥2 with verapamil or quinidine co-administration and (2) in vitro transport by 
P-gp expression systems, but not extensively metabolized.
b.
BCRP: (1) AUC fold-increase≥2 with pharmacogenetic alteration of ABCG2 (421C>A) and (2) in vitro 
transport by BCRP expression systems.
Abbreviations: AUC = area under the concentration-time curve; BCRP = breast cancer resistance protein; P-gp = p-
glycoprotein.

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APPENDIX G. SUPPLEMENTAL REQUIREMENTS FOR JAPAN ONLY
CLINICAL STUDY ORGANIZATION
The study organization details (Administrative Structure) will be maintained in the study Trial Master 
File.
GCP COMPLIANCE AND ETHICAL IMPLEMENTATION OF THE CLINICAL STUDY
This protocol has been established in accordance with an ethical principle based on the Helsinki 
Declaration, Pharmaceutical and Medical Device Act, a Pharmaceutical and Medical Device Act 
implementation ordinance, “the departmental order (GCP) about the criterion of the implementation of the 
clinical trials of medical supplies.”
In this clinical study, this protocol and ICH and local GCP must be followed.
ITEMS FOR EXPLANATION TO PATIENTS BY INFORMED CONSENT FORM
For informed consent by patients, the following items are explained using the informed consent form:
1.
That this is a clinical trial.
2.
The purpose of this clinical study.
3.
Study methodology.
4.
Expected study period for the patient.
5.
Planned patient number to participate in the clinical study.
6.
Expected benefit by investigational product for the subject’s physical/mental health (if it is not 
expected, the reason is explained) and, expected disadvantage to the subject.
7.
Existence or non-existence of treatment options other than investigational product, and expected 
important benefit and risk of the treatment options, as the clinical study subject is a patient.
8.
Compensation and treatment that the subject can receive if health damage related to the study 
occurs.
9.
Participation in the study is of the subject’s free-will and the subject can refuse or withdraw from 
participation in the study at any time.  The subject is not to be treated unfavorably or lose any 
advantage that he/she would receive when not participating in the study by refusing to participate 
or withdrawing from the study.
10. The fact that if information is obtained that may affect the subject's decision regarding continued 
participation in this study, that information will promptly be conveyed to the subject.
11. Condition and reason that participation in the study was discontinued.

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12. The monitor, auditor, IRB, and the regulatory authorities can review the original medical records.  
In such a case, the subject's privacy is to be preserved.  In addition, by applying his/her seal or 
signing the consent form, the subject permits such access.
13. Even if the results of the study are made public, the confidentiality of the subject’s identity will 
be preserved.
14. The details when it is necessary for the subject to bear the burden of expense.
15. The details when the subject is to be paid in money, etc.
16. The names, positions, and contact information for the primary investigator and the sub-
investigator.
17. The implementing medical institution’s consultation service for reference or to make contact if 
the subject would like to obtain further information regarding the study and the subject’s rights if 
health damage related to the study occurs.
18. Items that patients must follow:
!
A concrete antifertility method (condom and diaphragm, condom and spermicidal jelly, 
spermicide or film, diaphragm and spermicidal jelly, spermicide or film or intrauterine 
contraceptives).
19. The fact that when the subject is receiving treatment from another physician, the primary
investigator or sub-investigator will notify said physician that the subject is participating in the 
study.
20. Matters related to the type of IRB that reviews and discusses eligibility, etc. for said study and the 
reviews and discussions held in each IRB and other matters related to IRB regarding said study.
21. About the publication of the synopses of the record of procedure of the IRB, committee name list 
and the conference.  
THE IDENTIFICATION OF ANY DATA TO BE RECORDED ON THE CRFS, AND TO BE 
CONSIDERED TO BE SOURCE DATA
The following data will be recorded directly into the CRFs and will be considered source data:
!
Reasons for concomitance, concomitant medication/therapy prescribed at other hospitals
!
Presence or absence of AEs, name of AEs, serious/non-serious, treatment on study therapy, 
causal relationship with study drug, and reasons for terminating follow-up.
!
Reasons for admission and discharge from the hospital, reasons for discontinuation or 
termination from the study, and reasons for death. 
SAMPLE SIZE FOR JAPAN
Expected sample size for Japan: 15 - 20 cases in total.
CLINICAL STUDY PERIOD
Planned clinical study schedule: From May 2018 to April 2021.

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Amendment 3 Key Changes:
!
Removed references to NSCLC, gastric, and breast cancers and multiple myeloma population from 
sections throughout the protocol amendment as appropriate
!
Added information to timing of initiating the QD arm in relation to QOD dosing schedule 
!
Updated the language on women of childbearing potential and effective contraception inclusion criteria to 
comply with Clinical Trials Facilitation Group (CTFG) Guidelines
!
Added change to include tablets (i.e., number of tablets, description of packaging and storage 
information) about 4 mg and 20 mg TAS-120 tablets.
!
Updated information on assessment of overall response rate 
!
Revised section on determination of sample size
!
Updated guidelines for management of hyperphosphatemia
!
Added additional electrocardiogram (ECG) evaluations as appropriate
Amendment 4 Key Changes:
!
Updated clinical information for 2 clinical trials TAS-120-101 Phase 1/2 Trial TPU-TAS-120-101
[US/EU/Australia] and Phase 1 trial 10059010 [Japan]
!
Added rationale for the selection of QD dosing schedule 
!
Added a new intermediate dose level of 20 mg QD to enable a more precise determination of the 
Recommended Phase 2 Dose (RP2D).
Amendment 5 Key Changes:
!
Added specific cohorts of patients to be enrolled in the 4 groups in the Phase 1 Expansion 
!
Updated study endpoints for the Phase 1 Expansion and Phase 2 parts of the study including early 
progression rate (EPR) as a primary endpoint and added Response Assessment in Neuro-Oncology 
(RANO) as the guidelines for efficacy assessment for patients with glioblastoma multiforme (GBM) or 
grade III glioma, PFS and OS. 
!
Added efficacy and tumor assessments for brain tumors and added  RANO tumor assessment criteria for 
brain tumors. 
!
Updated the inclusion and exclusion criteria to further define patients included in Phase 1 Expansion and 
Phase 2
!
Revised guidelines for serum phosphorus monitoring and management of hyperphosphatemia
!
Provided the procedure for screening and identifying iCCA patients with tumors that have FGFR gene 
fusions in the Phase 2 part of the study.
!
!
Clarification of evaluations at visit schedules
!
Updated definitions of populations in statistical methods in both the Phase 1 Expansion and Phase 2 
!
Revised section on determination of sample size to further specify the sample size justification for the 
specific cohorts of patients to be enrolled in the Phase 1 Expansion and to provide sample size 
justification for patients enrolled in the Phase 2 part of the study.
Amendment 6 Key Changes:
!
Added an additional 4 cohorts of patients to be enrolled in the Phase 1 Expansion.
!
Added information that established 20 mg QD as the RP2D
!
Clarified Phase 2 primary objective, added a key secondary objective, other secondary objectives 
 
!
Updated the inclusion and exclusion criteria to further define patients in Phase 1 Expansion and Phase 2
!
Provided methods for prescreening testing of tumor samples for FGFR2 gene fusion before enrollment 
into Phase 2 
!
Removed TAS-120 capsule formulation as it is no longer applicable
!
Updated information on timing and fasting requirements to study drug administration procedures
!
Updated guidelines on Dose Hold, Dose Modifications and Dose Resumption  
!
Clarification of evaluations in visit schedules
CCI
CCI

TAS-120
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!
Updated information on statistical analysis of disease control rate (DCR), duration of response (DOR), 
PFS
!
Added assessments of and statistical analysis of Patient-Reported Outcome assessments.
!
Updated determination of sample size information to further specify the sample size justification for the 
specific cohorts of patients to be enrolled in the Phase 1 Expansion and to further specify sample size 
justification for patients enrolled in the Phase 2 part of the study.
Amendment 7 Key Changes:
Global
!
Reformatted and clarified study events tables to ensure consistency throughout the protocol.
!
Altered inclusion requirement for bilirubin to allow for serum or plasma assessment of bilirubin and to 
include patients with Gilbert’s syndrome and bilirubin up to 3 x upper limit of normal.
!
Clarified requirements for pregnancy testing of women of childbearing potential throughout the study.
!
Throughout the document, editorial changes, including elimination of errors or minor rewordings to 
improve clarity, were made as necessary.  The administrative alterations do not affect the planned 
conduct or analysis of the study.
Phase I Expansion
!
Added brief rationale for the design of the Phase I expansion portion of the study.
!
Enrollment suspended into Phase I expansion Groups 1, 3, 4, 6, and 8.
!
Refined criteria for enrollment into other groups in Phase I expansion, including:
o
Changing the FGFR requirement for Group 7 from “FGF9 or FGF19 amplifications” to “FGFR2 
amplifications.”
o
Changing the requirement for Group 5 from “grade III glioma” to “primary CNS tumors.”  
!
Changes were made to study objectives, statistical methods, and other sections of the protocol as 
necessary for consistency with the revised population of each subgroup in the Phase I expansion portion 
of the study.
Phase 2
!
Expanded eligibility requirements to allow all patients with FGFR2 rearrangements, rather than patients 
with FGFR2 gene fusions only.
!
Clarified requirements for tumor testing to determine and/or confirm study eligibility on the basis of 
FGFR2 gene fusion status.  
!
Clarified requirements for prior therapy (patients must have received at least one prior systemic 
gemcitabine-platinum therapy and have documented progression following the most recent prior therapy.
!
Added planned interim reviews of safety to be performed approximately every 3 months throughout the 
study, including brief description of the SRC that will perform these reviews.
Amendment 8 Key Changes:
!
Guidelines for management of hyperphosphatemia were updated to reflect analysis of most current 
available data.