Conditions: Cholangiocarcinoma Urothelial Cancer Advanced and Metastatic Cancer Patients With Tumors Harboring FGF/FGFR Tumors Primary CNS Tumors Breast Cancer Gastric Cancer
Keywords: FGF FGFR Futibatinib TAS-120
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 407
Healthy volunteers: no

Brief summary:
This is an open-label, nonrandomized, Phase 1/2 study for the fibroblast growth factor receptor (FGFR) inhibitor futibatinib (TAS-120). The purpose of the study is to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic, and anti-tumor activity of futibatinib in patients with advanced solid tumors with and without genomic FGF/FGFR abnormalities. The study will be conducted in 3 parts:

1. Dose escalation portion to determine the -Maximum Tolerated Dose and/ or Recommended Phase 2 Dose of futibatinib.
2. Phase 1 expansion portion to further evaluate the safety and efficacy of futibatinib in patients with tumors harboring FGF/FGFR aberrations, including patients with cholangiocarcinoma (CCA), primary central nervous system tumors, urothelial carcinoma, breast cancer, gastric cancer.
3. Phase 2 study portion to confirm objective response rate of futibatinib in intrahepatic CCA patients with tumors harboring FGFR2 gene rearrangements (incl fusions).

Detailed description:

Arms:
arm 1: Participants with or without fibroblast growth factor \[FGF\]/fibroblast growth factor receptor \[FGFR\] gene abnormalities received orally TAS-120 8 milligrams (mg) orally every other day (QOD; Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 2: Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 16 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 3: Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 24 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 4: Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 36 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 5: Participants with FGF/FGFR gene abnormalities received orally TAS-120 56 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 6: Participants with FGF/FGFR gene abnormalities received orally TAS-120 80 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 7: Participants with FGF/FGFR gene abnormalities received orally TAS-120 120 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 8: Participants with FGF/FGFR gene abnormalities received orally TAS-120 160 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 9: Participants with FGF/FGFR gene abnormalities received orally TAS-120 200 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 10: Participants with or without FGF/FGFR gene abnormalities received a dose between 4 mg orally once daily (QD) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 11: Participants with or without FGF/FGFR gene abnormalities received a dose between 8 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 12: Participants with or without FGF/FGFR gene abnormalities received a dose between 16 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 13: Participants with or without FGF/FGFR gene abnormalities received a dose between 20 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 14: Participants with or without FGF/FGFR gene abnormalities received a dose between 24 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 15: Participants with intra-hepatic or extrahepatic cholangiocarcinoma (iCCA or eCCA) harboring FGFR2 gene fusions or rearrangements and who were treated or not treated with prior FGFR inhibitors received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 16: Participants with primary central nervous system (CNS) tumors harboring FGFR gene fusions or FGFR1 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 17: Participants with advanced urothelial carcinoma harboring FGFR3 gene fusions or FGFR3 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 18: Participants with breast or gastric cancer with harboring FGFR2 amplification received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 19: Participants with tumor types harboring FGFR gene fusions or activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 20: Participants who were not included in Cohorts 1 to 5 received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 21: Participants with iCCA who were enrolled prior to the confirmation of the recommended Phase 2 dose (RP2D) received TAS-120 16 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 22: Participants with other tumor types who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. arm 23: Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Interventions: intervention 1: Futibatinib
Intervention descriptions: intervention 1: oral once daily dosing, 21-day cycle

Protocol document:
Prot_000.pdf: 
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 
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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).
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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 
fusions as a target for treating cholangiocarcinoma. Current Opinion in Gastroenterology, 
31(3), 264–268. http://doi.org/10.1097/MOG.0000000000000171
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 
cancer treatment-induced diarrhea. J Clin Oncol. 2004 Jul 15;22(14):2918-26.
16. Kris MG, Hesketh PJ, Somerfield MR, et al. American Society of Clinical Oncology 
guidelines for antiemetics in oncology: update 2006. J Clin Oncol. 2006 Jun 20;24:2932-47.
17. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid 
tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47.


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18. Barker FG, 2nd, Chang SM, Gutin PH, et al. Survival and functional status after resection of 
recurrent glioblastoma multiforme. Neurosurgery. 1998;42:709–20.
19. Gallego O. Nonsurgical treatment of recurrent glioblastoma. Curr Oncol. 2015 Aug;22(4): 
e273–e281.
20. Picca A, Berzero G, Bielle F, et al. FGFR1 actionable mutations, molecular specificities, and 
outcome of adult midline gliomas. Neurology. 2018;90:e2086-94.
21. Lasorella A, Sanson M, Iavarone A. FGFR-TACC gene fusions in human glioma. Neuro-
Oncology. 2017;19: 475-83.
22. Pearson A, Smyth E, Babina IS. High-level clonal FGFR amplification and response to 
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 
TAS-120, an irreversible fibroblast growth factor receptor (FGFR) inhibitor, in 
cholangiocarcinoma patients with FGFR pathway alterations who were previously treated 
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
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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.

SAP_001.pdf: 
Statistical Analysis Plan 
 
 
03.007A.01     
Page 1 of 64 
Sponsor Name: 
Taiho Oncology, Inc. 
Protocol Number and Title: 
 
TPU-TAS-120-101 
PHASE 1/2 STUDY OF TAS-120 IN PATIENTS WITH 
ADVANCED SOLID TUMORS HARBORING FGF/FGFR 
ABERRATIONS 
 
Protocol Version and Date: 
Final: 09 December 2013 
 
PROTOCOL AMENDMENT 1: 31 January 2014 
PROTOCOL AMENDMENT 1.1 (UK): 12 February 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 
 
INC Research Project Code: 
 
Author(s): 
 
 
 
  
 
 
   
SAP Version: 
  Version 3.3 (Phase I Dose Escalation) 
SAP Version Date:  
12-MAR-2018 
 
Notice of Confidential and Proprietary Information: 
The information contained in this document is confidential belonging to Taiho Oncology, Inc. 
Acceptance of this document constitutes agreement by the recipient that no information 
contained herein will be published or disclosed without prior written authorization from an 
official of Taiho Oncology, Inc.  However, this document may be disclosed to appropriate 
Institutional Review Board and Ethics Committees or duly authorized representatives of a 
national regulatory authority under the condition that they are requested to keep it confidential. 
In the event of an actual or suspected breach of this obligation, INC Research should be notified 
promptly. 
 
PPD
PPD
CCI
CCI


PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
CCI
CCI


PPD
PPD
CCI
CCI
PPD


INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 4 of 64 
TABLE OF CONTENTS 
1. 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS ............... 8 
2. 
PURPOSE ..................................................................................................... 12 
2.1. 
Responsibilities ................................................................................................................. 12 
2.2. 
Timings of Analyses .......................................................................................................... 12 
3. 
STUDY OBJECTIVES ................................................................................... 13 
3.1. 
Phase I Dose Escalation ................................................................................................... 13 
3.1.1. 
Primary Objective ............................................................................................................ 13 
3.1.2. 
Secondary Objectives ...................................................................................................... 13 
4. 
STUDY DESIGN ............................................................................................ 14 
4.1. 
Brief Description ................................................................................................................ 14 
4.1.1. 
Definitions of DLT and MTD ............................................................................................ 16 
4.1.2. 
Dose Escalation Scheme ................................................................................................ 17 
4.1.3. 
Replacement Criteria ....................................................................................................... 18 
4.2. 
Subject Selection ............................................................................................................... 18 
4.2.1. 
Inclusion Criteria .............................................................................................................. 18 
4.2.2. 
Exclusion Criteria ............................................................................................................. 19 
4.3. 
Determination of Sample Size .......................................................................................... 21 
4.4. 
Treatment Assignment & Blinding ................................................................................... 22 
4.5. 
Administration of Study Medication ................................................................................ 22 
4.6. 
Study Procedures and Flowchart ..................................................................................... 22 
5. 
ENDPOINTS .................................................................................................. 27 
5.1. 
Safety Endpoints ................................................................................................................ 27 
5.1.1. 
Adverse Events ............................................................................................................... 27 
5.1.2. 
Laboratory Evaluations .................................................................................................... 27 
5.1.3. 
Vital Signs and Body Weight ........................................................................................... 27 
5.1.4. 
ECG ................................................................................................................................. 27 
5.1.5. 
Physical Examination ...................................................................................................... 27 
CCI
CCI


INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 5 of 64 
5.2. 
Pharmacokinetic Endpoints ............................................................................................. 28 
5.3. 
Pharmacodynamic Endpoints .......................................................................................... 28 
5.4. 
Efficacy Endpoints ............................................................................................................. 28 
6. 
ANALYSIS SETS .......................................................................................... 30 
6.1. 
Safety Population ............................................................................................................... 30 
6.2. 
DLT Evaluable Population ................................................................................................ 30 
6.3. 
PK and Pharmacodynamic Population  ........................................................................... 30 
6.4. 
Efficacy Population ............................................................................................................ 30 
6.5. 
Protocol Deviations ........................................................................................................... 30 
7. 
GENERAL ASPECTS FOR STATISTICAL ANALYSIS ................................ 31 
7.1. 
General Methods ................................................................................................................ 31 
7.2. 
Key Definitions ................................................................................................................... 32 
7.2.1. 
First Dose Date ................................................................................................................ 32 
7.2.2. 
Cut-Off Date of Final Analysis ......................................................................................... 32 
7.2.3. 
Last Dose Date ................................................................................................................ 32 
7.2.4. 
Study Day ........................................................................................................................ 32 
7.2.5. 
Treatment Duration .......................................................................................................... 32 
7.3. 
Missing Data ....................................................................................................................... 32 
8. 
DEMOGRAPHIC, OTHER BASELINE CHARACTERISTICS AND 
MEDICATION ....................................................................................................... 34 
8.1. 
Subject Disposition and Withdrawals .............................................................................. 34 
8.2. 
Demographic and Other Baseline Characteristics ......................................................... 34 
8.3. 
Medical History .................................................................................................................. 34 
8.4. 
Other Baseline Disease Characteristics .......................................................................... 34 
8.5. 
Medication .......................................................................................................................... 35 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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9. 
EFFICACY ..................................................................................................... 36 
9.1. 
Best Overall Response ...................................................................................................... 37 
9.2. 
Objective Response Rate .................................................................................................. 39 
9.3. 
Disease Control Rate .............................................................. Error! Bookmark not defined. 
9.4. 
Duration of Response........................................................................................................ 39 
9.5. 
Progression Free Survival ..................................................... Error! Bookmark not defined. 
9.6. 
Time to PRogression .............................................................. Error! Bookmark not defined. 
10. 
SAFETY ..................................................................................................... 40 
10.1. 
Extent of Exposure ............................................................................................................ 40 
10.2. 
Dose limiting toxicity ......................................................................................................... 41 
10.3. 
Adverse Events .................................................................................................................. 41 
10.4. 
Laboratory Evaluations ..................................................................................................... 43 
10.5. 
Vital Signs and Body Weight ............................................................................................ 44 
10.6. 
ECG ..................................................................................................................................... 45 
10.7. 
Physical Examination ........................................................................................................ 45 
10.8. 
Performance Status ........................................................................................................... 45 
10.9. 
Ophthalmological Examination ........................................................................................ 46 
10.10. 
Neurological Examination ............................................................................................ 46 
10.11. 
Pregnancy Test .............................................................................................................. 46 
11. 
PHARMACOKINETICS ............................................................................. 47 
11.1. 
sample collection ............................................................................................................... 47 
11.2. 
PK parameters to be calculated ....................................................................................... 47 
11.3. 
Plasma and urine Concentration data ............................................................................. 48 
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Statistical Analysis Plan 
 
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11.4. 
PK sample collection time ................................................................................................ 49 
11.5. 
calculation of plasma pk parameters ............................................................................... 49 
11.6. 
calculation of urine pk parameters .................................................................................. 50 
11.7. 
Dose proportionality .......................................................................................................... 51 
11.8. 
accumulation ratio ............................................................................................................. 52 
12. 
PHARMACODYNAMICS ........................................................................... 53 
12.1. 
PD endpoints ...................................................................................................................... 53 
12.2. 
sample collection ............................................................................................................... 53 
12.3. 
pharmacodynamic parameters summarization .............................................................. 54 
13. 
PHARMACOGENOMICS ........................................................................... 55 
14. 
INTERIM ANALYSES ................................................................................ 56 
15. 
CHANGE FROM ANALYSIS PLANNED IN PROTOCOL ......................... 57 
16. 
REFERENCE LIST .................................................................................... 58 
17. 
PROGRAMMING CONSIDERATIONS ...................................................... 59 
17.1. 
General Considerations .................................................................................................... 59 
17.2. 
Table, Listing, and Figure Format .................................................................................... 59 
17.2.1. 
General ........................................................................................................................ 59 
17.2.2. 
Headers ....................................................................................................................... 60 
17.2.3. 
Display Titles ............................................................................................................... 60 
17.2.4. 
Column Headers ......................................................................................................... 60 
17.2.5. 
Body of the Data Display ............................................................................................. 61 
17.2.6. 
Footnotes .................................................................................................................... 63 
18. 
QUALITY CONTROL ................................................................................. 64 
 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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1. 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation 
Description 
λZ 
Elimination rate constant 
β-HCG 
Beta-human chorionic gonadotropin 
Ae% 
Urinary excretion rate as % of dose 
AE 
Adverse Event 
ALT (SGPT) 
Alanine Aminotransferase 
ANC 
Absolute Neutrophil Count 
APTT 
Activated partial thromboplastin time 
AST (SGOT) 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
AUC0-24 
Area under the concentration-time curve up to 24 hours 
AUC0-48 
Area under the concentration-time curve up to 48 hours 
AUC0-last  
Area under the concentration-time curve up to the time of 
last quantifiable concentration 
AUC0-inf  
Area under the concentration-time curve up to infinity on 
C1D1 
BUN 
Blood urea nitrogen 
CI 
Confidence Interval 
CL/F 
Oral (or fractional) Clearance 
CLr 
Renal clearance 
Cmax 
Maximum observed plasma concentration 
CK 
Creatine kinase 
CK-MB 
Creatine kinase (isoform heart muscle) 
CK-MM 
Creatine kinase (isoform skeletal muscle) 
CR 
Complete Response 
CRF 
Case Report Form 
CRP 
C-reactive protein 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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Abbreviation 
Description 
CSF 
Cerebral Spinal Fluid 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
Coefficient of Variation 
DCR 
Disease Control Rate 
DLT 
Dose Limiting Toxicity 
DR 
Duration of response 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EFF 
Efficacy Population 
FGF/FGFR 
Fibroblast growth factor / Fibroblast growth factor receptor 
FLC 
Free light chain 
GnRH 
Gonadotropin-releasing hormone 
ICH 
International Conference on Harmonization 
IMP 
Investigational Medicine Product 
IMWG 
International Myeloma Working Group 
INR 
International normalized ratio 
IU 
International Units 
LH-RH 
Luteinizing hormone-releasing hormone 
Max 
Maximum 
MedDRA 
Medical Dictionary for Regulatory Activities 
Min 
Minimum 
MRT 
Mean residence time up to infinity 
MTD 
Maximum Tolerated Dose 
NCI 
National Cancer Institute 
NSCLC 
Non-small cell lung cancer 
NYHA 
New York Heart Association 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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Page 10 of 64 
Abbreviation 
Description 
ORR 
Objective response rate 
PD 
Progressive Disease 
PFS 
Progression-free survival 
PGx 
Pharmacogenomics 
PK 
Pharmacokinetic(s) 
PR 
Partial Response 
PT 
Preferred Term 
QC 
Quality Control 
QD 
Once daily (continuous) dosing 
QOD 
3 times a week (Monday, Wednesday, and Friday) dosing 
QTc 
Corrected QT Interval 
QTcB 
Bazett’s Correction of QT Interval 
QTcF 
Fridericia’ Correction of QT Interval 
RAUC 
Accumulation ratio calculated based on AUC0-last 
RBC 
Red Blood Cell 
RCmax 
Accumulation ratio calculated based on Cmax 
RDI 
Relative Dose Intensity 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RP2D 
Recommended Phase 2 Dose 
RSQ 
R-Square 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
sCR 
Stringent complete response 
SD 
Stable Disease  
SE 
Standard Error 
SFLC 
Serum free light chain 
SI 
Standard International System of Units 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 11 of 64 
Abbreviation 
Description 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SPEP 
Serum Protein Electrophoresis 
TEAE 
Treatment Emergent Adverse Event 
TLF 
Table, Listing and Figure 
TOI 
Taiho Oncology Inc. 
TPC 
Taiho Pharmaceutical, Co., Ltd. 
T1/2 
Half-life time 
Tmax 
Time to reach maximum concentration in plasma 
ULN 
Upper Limit of Normal 
UPEP 
Urine Protein Electrophoresis 
Vd/F 
Apparent volume of distribution  
WBC 
White blood cell 
WHO 
World Health Organization 
 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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2. 
PURPOSE 
The purpose of this statistical analysis plan (SAP) is to ensure that the summary tables, 
data listings and figures (TLFs) which will be produced, and the statistical 
methodologies that will be used, are complete and appropriate to allow valid 
conclusions regarding the study objectives. 
2.1. 
RESPONSIBILITIES 
INC Research Biostatics Group will perform the statistical analyses and are responsible 
for the production and quality control of all tables, listings and figures (TLFs). INC 
Research Biostatics Group will perform PK analysis following this SAP with the guidance 
and the preliminary result supplied by Taiho Oncology, Inc. The preliminary result Taiho 
will provide are the ones associated with plasma samples only. 
 
2.2. 
TIMINGS OF ANALYSES 
In this study, patients will receive the study medication according to the proposed 
treatment schedule until disease progression (PD), occurrence of intolerable side 
effects, decision to discontinue treatment by the Investigator, withdrawal of consent by 
patient, or other criteria for discontinuation are met (see protocol Section 6.3, 
Discontinuation Criteria). A patient is considered discontinued from study treatment 
when TAS-120 is discontinued. 
For the purpose of the final analyses for dose escalation phase, the dose escalation 
phase will be considered completed when all patients in phase 1 dose escalation have 
discontinued from treatment or have sufficient follow-up (more than 6 months) from 
the date of the first treatment with TAS-120 of the last patient enrolled, whichever 
occurs first. 
 
 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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3. 
STUDY OBJECTIVES 
3.1. 
PHASE I DOSE ESCALATION 
3.1.1. 
Primary Objective 
• 
To investigate the safety and to determine the maximum tolerated dose (MTD) 
and the recommended Phase 2 dose (RP2D) of TAS-120 and its associated dosing 
schedule (3 times a week [Monday, Wednesday, and Friday] [QOD]) or once daily 
[QD]) in patients with advanced solid tumors with or without FGF/FGFR 
abnormalities who have failed all standard therapies or for whom standard 
therapy does not exist. 
3.1.2. 
Secondary Objectives 
• 
To investigate the clinical pharmacokinetics (PK) of TAS-120. 
• 
To investigate the clinical pharmacodynamics of TAS-120. 
• 
To determine any preliminary antitumor activity observed with TAS-120. 
 
 
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Protocol: TPU-TAS-120-101 
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Statistical Analysis Plan 
 
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4. 
STUDY DESIGN 
4.1. 
BRIEF DESCRIPTION 
This is a phase 1/2 study of TAS-120 in patients with advanced solid tumors harboring 
FGF/FGFR aberrations. TAS-120 is administered once a day, in the morning (Phase 1 
Dose Escalation only), orally, 3 times a week (i.e., QOD, Monday, Wednesday, and 
Friday) or everyday (i.e., QD) in patients. The study will be conducted in 3 parts: a 
Phase 1 Dose-Escalation part to determine the MTD and RP2D of TAS-120 in 2 dose 
schedules (QOD or QD), a Phase 1 Expansion part and a Phase 2 part to further evaluate 
the efficacy and safety of the RP2D of TAS-120 and dose schedule. Phase 1 expansion 
and Phase 2 will be planned in a separate SAP.  
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 of TAS-120 until at least one of the 
discontinuation criteria is met (see Protocol Section 6.3).  
Phase 1 Dose-Escalation  
TAS-120 is administered to cohorts of patients with advanced solid tumors at up to 10 
escalating dose levels (Table 1). At all dose levels, 3 to 6 patients with advanced solid 
tumors is to enrolled in each cohort sequentially. Dose escalation begins with QOD 
dosing. When QOD dose escalation reaches Dose Level 5, Dose Level 1 of QD dosing is to 
be initiated. For the QD arm, TAS-120 is administered at up to 11 escalating dose levels 
in 21- day treatment cycles.  
At Dose Level 1 (for both arms), the patients start TAS-120 treatment sequentially at 
intervals of a minimum of 1 week. Beginning with Dose Level 5 in both arms, patient 
eligibility criteria is restricted only to patients with an FGF/FGFR abnormality. 
Escalation to each subsequent dose level occur only after the current dose level is 
found to be safe according to the protocol criteria (“3 + 3” design). Intrapatient dose 
escalation is not allowed. 
The MTD is defined as the highest dose level at which less than 33% of the patients 
experience a dose-limiting toxicity (DLT) during Cycle 1 (See 4.1.1. Definitions of DLT 
and MTD). At least 6 evaluable patients is to be enrolled at the MTD level. The RP2D is 
equal to or less than the MTD, and its associated dosing schedule is selected based on 
the safety, PK, pharmacodynamic, and preliminary efficacy data observed during Phase 
1 Dose Escalation.  
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
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Based on investigator and sponsor assessment, if further clinical evaluation is required, 
additional 3 to 6 patients may be added to any cohort.  
Table 1:  Dose Levels 
QOD Dose 
Level 
Dose in mg 
(QOD) 
Patient population 
QD  
Dose Level 
Dose in 
mg (QD) 
Patient population 
1 
8 
With or without 
FGF/FGFR abnormalities 
--- 
--- 
--- 
2 
16 
With or without 
FGF/FGFR abnormalities 
--- 
--- 
--- 
3 
24 
With or without 
FGF/FGFR abnormalities 
--- 
--- 
--- 
4 
36 
With or without 
FGF/FGFR abnormalities 
--- 
--- 
--- 
5 
56 
With FGF/FGFR 
abnormalities 
1 
4 
With or without 
FGF/FGFR 
abnormalities 
6 
80 
With FGF/FGFR 
abnormalities 
2 
8 
With or without 
FGF/FGFR 
abnormalities 
7 
120 
With FGF/FGFR 
abnormalities 
3 
16 
With or without 
FGF/FGFR 
abnormalities 
 
 
 
3.5 
20a 
With FGF/FGFR 
abnormalities 
8 
160 
With FGF/FGFR 
abnormalities 
4 
24 
With or without 
FGF/FGFR 
abnormalities 
9 
200 
With FGF/FGFR 
abnormalities 
5 
36 
With FGF/FGFR 
abnormalities 
10 
240 
With FGF/FGFR 
abnormalities 
6 
56 
With FGF/FGFR 
abnormalities 
- 
- 
--- 
7 
80 
With FGF/FGFR 
abnormalities 
- 
- 
--- 
8 
120 
With FGF/FGFR 
abnormalities 
- 
- 
--- 
9 
160 
With FGF/FGFR 
abnormalities 
- 
- 
--- 
10 
200 
With FGF/FGFR 
abnormalities 
- 
- 
--- 
11 
240 
With FGF/FGFR 
abnormalities 
Abbreviations: QD = once daily; QOD = 3 times a week (Monday, Wednesday, and Friday); FGF = fibroblast 
growth factor; FGFR = fibroblast growth factor receptor. 
a Intermediate dose level added for dose optimization in Amendment 4. 
Overall Study Design 
 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
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Statistical Analysis Plan 
 
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4.1.1. 
Definitions of DLT and MTD 
Only drug-related toxicities during the Cycle 1 are considered in the assessment of 
DLTs.  
A DLT is defined as the following:  
a) ≥ Grade 3 nonhematologic toxicity (excluding nausea/vomiting, diarrhea) 
b) ≥ Grade 3 nausea/vomiting lasting > 48 hours and uncontrolled by aggressive 
antiemetic therapy, including serotonin 5-HT3 receptor antagonists (e.g., 
ondansetron) 
Enrollment 
Phase 1 Dose Escalation (QOD) 
DLT, safety, PK, 
Confirm eligibility criteria were met 
Phase 1 Expansion (QD) 
ffi
f
Phase 2 (QD) 
Efficacy, Safety 
Phase 1 Dose Escalation (QD) 
DLT, safety, PK, pharmacodynamic, 
and efficacy 
Abbreviations: DLT = dose-limiting toxicity; PK = pharmacokinetics; QD = once daily 
(continuous) dosing; QOD = 3-times-a-week (Monday, Wednesday, Friday) dosing.  
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c) ≥ Grade 3 diarrhea lasting > 48 hours and unresponsive to antidiarrheal 
medication 
d) Grade 4 neutropenia lasting > 7 days 
e) Febrile neutropenia (absolute neutrophil count [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). 
f) Grade 4 thrombocytopenia or Grade 3 thrombocytopenia associated with 
bleeding and requiring blood transfusion 
g) Corneal disorder worsening by 1 grade or more 
h) Hyperphosphatemia: any increase of phosphorus 
≥ 9mg/dL or an increase of 
phosphorus ≥ 7mg/dL lasting for 7 days or more despite phosphate -lowering 
therapy for 7 days as outlined in Appendix C or according to institutional 
guidelines. 
i) Increase of creatinine (> 1.5 × upper limit of normal [ULN]) lasting for 7 days or 
more associated with serum phosphorus > 5.5 mg/dL despite phosphate-lowering 
therapy for 7 days and/or calcium × phosphorus > 55 mg/dL despite phosphate-
lowering therapy for 7 days.  
j) Grade 2 hypercalcemia for > 7 days or Grade 3 hypercalcemia 
k) Ectopic de novo calcification in soft tissues, as determined by the investigator 
l) Any > Grade 2 drug-related toxicity that prevents completion of Cycle 1 (> 80% 
administration of intended dose of TAS-120) 
m) Inability to start Cycle 2 within 2 weeks of schedule due to a > Grade 2 drug-
related toxicity. 
The MTD of TAS-120 is defined as the highest dose level at which less than 33% of the 
patients experience a DLT during Cycle 1. At least 6 evaluable patients will be enrolled 
to establish the MTD. 
4.1.2. 
Dose Escalation Scheme 
A “3 + 3” design scheme is used for dose escalations. A minimum of 3 patients is treated 
at each dose level prior to escalation to the next cohort. If none of the initial 3 patients 
treated at the first dose level experience a DLT during Cycle 1 of therapy, the dose is to 
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
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be escalated to the next level. If a DLT is observed in 1 of the first 3 patients, then 3 
additional patients is to be enrolled at the same dose level. If none of the 3 additional 
patients have DLTs after they all complete Cycle 1 of treatment, the dose is to be 
escalated to the next level. If ≥ 1 of the additional 3 patients develop a DLT, then dose 
escalation ceases and at least a total of 6 evaluable patients is to be enrolled in the 
previous dose level to establish the MTD. If 2 of the first 3 patients in a cohort 
experience DLTs, then dose escalation ceases and at least a total of 6 evaluable 
patients is to be enrolled in the previous dose level to establish the MTD. No 
intrapatient dose escalation is allowed. 
Based on investigator and sponsor assessment, if further safety evaluations are 
required, additional 3 to 6 patients may be added to any cohort for a total of up to 12 
patients per cohort. 
4.1.3. 
Replacement Criteria 
During Phase 1 Dose Escalation, patients who do not complete Cycle 1 of therapy 
because of a DLT will be considered evaluable and will not be replaced. Patients who 
withdraw for any reason other than a DLT during Cycle 1, and who have not received at 
least 80% of the intended TAS-120 dosage, is considered inevaluable and is to be 
replaced.  
4.2. 
SUBJECT SELECTION 
4.2.1. 
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 of age. 
3. Phase 1 Dose Escalation: 
Patients with histologically or cytologically confirmed advanced, measurable or 
non-measurable (as defined by Response Evaluation Criteria in Solid Tumors 
[RECIST] guidelines [version 1.1, 2009]) metastatic solid tumor(s) who have 
failed all standard therapies or for whom standard therapy does not exist. 
Starting with Dose Level 5 of each dosing schedule, only patients with locally 
diagnosed amplification, mutation, translocation or other associated 
abnormalities of FGF/FGFR will be enrolled (see Protocol Section 8.12, 
Pharmacogenomic (FGF/FGFR) Analysis). 
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4. May have received any number of prior therapies for advanced or metastatic 
disease. 
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 on Day 1 
of Cycle 1 (see Protocol Appendix A, ECOG Performance Status). 
6. Able to take medications orally (e.g., no feeding tube). 
7. Adequate organ function as defined by the following criteria: 
8. 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. 
a. Total serum bilirubin ≤ 1.5 × ULN. 
b. Absolute neutrophil count ≥1 500/mm3 (i.e., ≥ 1.5 × 109/L by 
International Units [IU]) (excluding measurements obtained within 7 days 
after administration of granulocyte colony-stimulating factor [G-CSF]). 
c. Platelet count ≥ 100 000/mm3 (IU: ≥ 100 × 109/L) (excluding 
measurements obtained within 7 days after a transfusion of platelets). 
d. Hemoglobin ≥ 8.0 g/dL (excluding measurements within 4 weeks of a 
transfusion of packed red blood cells [RBCs] or whole blood). 
e. Serum phosphorus ≤ ULN.  
f. Serum calcium ≤ ULN. 
g. Creatinine < 1.5 × ULN.  
9. Women of child-bearing potential must have a negative pregnancy test (urine or 
serum) within 7 days prior to administration of the first dose of TAS-120. Both 
males and females of reproductive potential must agree to use adequate birth 
control during the study and for 6 months after the last dose of TAS-120. Female 
patients are not considered to be of child bearing potential if they have a history 
of tubal ligation or hysterectomy or are post-menopausal with a minimum of 1 
year without menses. 
10. Willing and able to comply with scheduled visits and study procedures.  
4.2.2. 
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 endocrine alteration of calcium-phosphorus 
homeostasis. 
2. History and/or current evidence of ectopic mineralization/calcification including 
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but not limited to soft tissue, kidneys, intestine, or myocardia and lung with the 
exception of calcified lymph nodes and asymptomatic arterial calcification.  
3. Current evidence of corneal disorder/keratopathy including but not limited to 
bullous/band keratopathy, corneal abrasion, inflammation/ulceration, 
keratoconjuctivitis, etc., confirmed by ophthalmologic examination. 
4. History or current evidence of cardiac arrhythmia and/or conduction 
abnormality. 
5. Corrected QT interval (QTc) > 470 msec on electrocardiogram (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 prior to the first dose of 
TAS-120 or limited field radiotherapy within 2 weeks prior to the first 
dose of TAS-120.    
c. Any noninvestigational anticancer therapy within 3 weeks prior to TAS-
120 administration (mitomycin within prior 5 weeks). Concomitant 
treatment of Gonadotropin-Releasing Hormone (GnRH) agonists or 
Luteinizing Hormone-Releasing Hormone (LH-RH) agonists is permitted in 
prostate cancer patients if they have been on therapy for more than 6 
months and tolerating the therapy. 
d. Any medication administered within 7 days prior to first dose of TAS-120 
that is known to affect QT interval or to be arrhythmogenic such as, but 
not limited to, the following drugs 
(http://crediblemeds.org/pdftemp/pdf/CompositeList.pdf): 
i. Ondansetron 
ii. Erythromycin 
iii. Droperidol 
iv. Halofantrine 
e. Any investigational agent received either concurrently or within the 
previous 30 days. 
7. A serious illness or medical condition(s) including, but not limited to, the 
following: 
a) Known brain metastasis unless patient is clinically stable and off 
corticosteroids for ≥ 2 months. 
b) Known leptomeningeal metastasis.  
c) Known acute systemic infection. 
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Statistical Analysis Plan 
 
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d) Myocardial infarction, severe/unstable angina, symptomatic congestive 
heart failure (New York Heart Association [NYHA] Class III or IV (see 
protocol Appendix B, New York Heart Association [NYHA] Classification) 
within the previous 6 months; if > 6 months cardiac function must be 
within normal limits and the patient must be free of cardiac-related 
symptoms. 
e) Chronic nausea, vomiting, or diarrhea considered to be clinically 
significant in the opinion of the investigator. 
f) Known human immunodeficiency virus or acquired immunodeficiency 
syndrome-related illness, or a history of serum positivity to hepatitis B or 
C.  
g) Congenital long QT syndrome, or any known history of torsade de pointes, 
or family history of unexplained sudden death.  
h) Other severe acute or chronic medical or psychiatric condition or 
laboratory abnormality that may increase the risk associated with study 
participation or TAS-120 administration, or may interfere with the 
interpretation of study results, and in the judgment of the investigator 
would make the patient inappropriate for entry into this study. 
8. Known hypersensitivity to TAS-120 or any drugs similar to it in structure or class. 
9. Pregnant or lactating female. 
4.3. 
DETERMINATION OF SAMPLE SIZE 
 
 
  
 
 
 
 
 
 Approximately 60 to 120 evaluable patients is to 
be enrolled in Phase 1 Dose Escalation, including replacements for patients not meeting 
the DLT-evaluable criteria assuming that all cohorts are filled. In addition, based on 
investigator and sponsor assessment, if further safety evaluations are required an 
additional 3 to 6 patients may be added to any cohort. 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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4.4. 
TREATMENT ASSIGNMENT & BLINDING 
This is an open-label, non-randomized study. Treatment for patients is assigned 
according to the study design for sequential dose escalation phase. 
4.5. 
ADMINISTRATION OF STUDY MEDICATION 
Each treatment cycle is 21 days in duration. During Phase 1 Dose Escalation, TAS-120 is 
given to patients in each cohort of escalating doses to determine the MTD.  
All patients receive TAS-120 at the assigned dose, orally, once a day, 3 times a week 
(Monday, Wednesday, and Friday) [QOD] or continuously (once daily dosing [QD]) in 21-
day treatment cycles. TAS-120 is taken with a glass of water on an empty stomach (2 
hours after and 1 hour before a meal). 
4.6. 
STUDY PROCEDURES AND FLOWCHART 
The study assessments are summarized in Table 2A. 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 and on the last 
Wednesday of Cycle 1 (QOD) or Day 21 of Cycle 1 (QD). A window of ± 7 days is 
allowable for computed tomography (CT) scans and follow-up visits. These windows are 
not applicable during Screening. If any Screening assessments are repeated on Day 1 of 
Cycle 1.  
 
 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.0, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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Table 2A: Study Schedule for Phase 1 Dose Escalation  
 
Screening Period 
On-Treatment Period 
End-of-Treatment 
Visita 
 
Screening Day 
Cycle 1 (21 days) 
Subsequent Cycles (21 days) 
30-Day Safety 
Follow-up Visitb 
Day of Cycle 
Day of Cycle 
Procedure 
 
-28 to -1 
 
-7 to -1 
 
1 
 
8 
 
15 
Last Wednesday of 
Cycle 1 (QOD) or 
Day 21 (QD)c 
 
1 
 
8 
 
15 
 
21 
 
Sign ICF 
X 
 
 
 
 
 
 
 
 
 
 
Review inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
ESS 
 
X 
 
 
 
 
 
 
 
 
 
Physical examination 
 
X 
 
 
 
 
Xd 
 
 
 
X 
Vital signse and weight 
 
X 
 
 
 
 
Xd 
 
 
 
X 
Ophthalmological examinationf 
X 
 
 
 
 
 
 
Xf 
 
Neurological examinationg 
X 
 
 
 
 
 
 
 
 
 
 
Height 
 
X 
 
 
 
 
 
 
 
 
 
ECOG Performance Status 
X 
 
X  
 
 
 
Xd 
 
 
 
X 
Electrocardiogram 
X 
 
Xh 
 
 
Xh 
Xh 
 
 
 
X 
Hematology and coagulationi 
 
X 
X 
X 
X 
 
X 
Xi 
X 
 
X 
Serum chemistryj 
 
X 
X 
X 
X 
 
X 
Xj 
X 
 
X 
Urinalysis 
 
X 
 
 
 
 
Xd 
 
 
 
X 
Pregnancy test  
 
X 
 
 
 
 
 
 
 
 
 
PK/pharmacodynamic blood 
samplingk 
 
 
X 
 
 
X 
 
 
 
 
 
PK urine sampling (QOD only)l 
 
 
X 
 
 
 
 
 
 
 
 
Pharmacodynamic urine samplingm 
 
 
X 
 
 
X 
 
 
 
 
 
Prior and concomitant 
medicationsn 
X 
 
 
 
 
 
 
 
 
 
X 
AE/toxicity assessmento 
 
 
X 
 
 
 
 
 
 
 
X 
Tumor assessment/scansp 
X 
 
 
 
 
 
 
 
 
X 
X 
TAS-120 treatmentq 
 
 
X 
 
 
 
X 
 
 
 
 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 24 of 64 
 
Screening Period 
On-Treatment Period 
End-of-Treatment 
Visita 
 
Screening Day 
Cycle 1 (21 days) 
Subsequent Cycles (21 days) 
30-Day Safety 
Follow-up Visitb 
Day of Cycle 
Day of Cycle 
Procedure 
 
-28 to -1 
 
-7 to -1 
 
1 
 
8 
 
15 
Last Wednesday of 
Cycle 1 (QOD) or 
Day 21 (QD)c 
 
1 
 
8 
 
15 
 
21 
 
Tumor tissue sampling for PGx 
analysis  
Xr 
 
 
 
 
 
 
 
 
 
 
Abbreviations: AE = adverse event; ECOG = Eastern Cooperative Oncology Group; ESS = existing signs and symptoms; ICF = informed consent 
form; PGx = pharmacogenomic; PK = pharmacokinetic; QD = once daily (continuous) dosing; QOD = 3-times-a-week (Monday, Wednesday, 
Friday) dosing. 
a End of treatment (EOT) Visit (optional): If the decision to discontinue TAS120 is made for reasons other than radiologic disease 
progression, an EOT visit should be considered to capture the status of the patient at the time of discontinuation. At the EOT visit, serum 
chemistry, hematology, and coagulation testing will be performed along with any other test deemed clinically indicated by the 
investigator (e.g., electrocardiogram, ophthalmological examination, neurological examination). The EOT visit should occur within 3 days 
of the decision to discontinue treatment. The EOT visit does not replace the 30-day safety follow-up visit. 
b 30-Day Safety Follow-up Visit: 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 before the start of new anticancer therapy. See Section 10.17, 30-Day Safety Follow-up. 
c Last Wednesday of Cycle 1 (QOD) or Day 21 (QD): only for patients enrolled in Phase 1 Dose Escalation but not required for patients 
enrolled in Phase 1 Expansion and Phase 2. 
d Physical Exam, Vital Signs, Weight, ECOG Performance Status, and Urinalysis: Beginning with Cycle 2 and for all subsequent cycles, obtain 
within 24 hours prior to Day 1 TAS-120 administration. 
e Vital Signs: Heart rate, blood pressure, body temperature, and respiration rate. 
f Ophthalmological Examination: Obtain at Screening, at 4 to 6 weeks after starting treatment with TAS-120, and repeat if clinically 
indicated using the same testing methods. For further details on the scope of the examination, see Section 10.8, Ophthalmological 
Examination. 
g Neurological Examination: Obtain at Screening and repeat if clinically indicated using the same testing methods employed at Screening, 
in addition to any other clinically indicated examinations. For further details on the scope of the examination, see Section 10.9, 
Neurological Examination. 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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h Electrocardiogram (ECG) Evaluation: On Day 1 and on the last Wednesday of Cycle 1 (Phase 1 Dose Escalation only, QOD arm), obtain 2 
hours after the TAS-120 dose. On Day 1 and Day 21 of Cycle 1 (Phase 1 Dose Escalation only, QD arm), obtain at 2 hours after the TAS-120 
dose. For all subsequent cycles starting with Cycle 3 (Phase 1 Dose Escalation) or Cycle 2 (Phase 1 Expansion and Phase 2), ECG should be 
performed on Day 1 (± 3 days) of each cycle obtained 2 at hours after the TAS-120 dose, see Section 10.7, Electrocardiogram (ECG) 
Evaluation. 
i Hematology and Coagulation: Obtain within 24 hours prior to TAS-120 administration on Day 1 of each cycle, and anytime on Day 8 and 
Day 15 of Cycle 1 and Cycle 2 (± 3 days). Starting with Cycle 3, the Day 8 assessment is no longer required, unless deemed clinically 
indicated by the investigator. For more details, see Section 10.10.1, Hematology and Coagulation. 
j Serum Chemistry: Obtain within 24 hours prior to TAS-120 administration on Day 1 of each cycle, and anytime on Day 8 and Day 15 of 
Cycle 1 and Cycle 2 (± 3 days). For more details, see Section 10.10.2. Starting with Cycle 3, the Day 8 assessment is no longer required, 
unless deemed clinically indicated by the investigator or if previous serum chemistries showed an elevation of phosphorus that required 
action as specified Section 9.1.1.1.1 . 
k PK/Pharmacodynamic Blood Sampling: During Phase 1 Dose Escalation, collect PK/pharmacodynamic blood samples at the following time 
points on Day 1 and on the last Wednesday of Cycle 1 (QOD) or on Day 1 and Day 21 of Cycle 1 (QD): immediately prior to dosing (0 hour) 
and postdose at 30 minutes and 1, 2, 3, 4, 6, 8, 12, 24 (QOD and QD), and 48 hours (QOD only). The 48-hour postdose sample (QOD) and 
the 24-hour postdose sample (QD) must be collected prior to TAS-120 administration on that day. See Section 10.13.1, 
Pharmacokinetic/Pharmacodynamic Blood Sample Collection. 
l PK Urine Sampling (QOD only): During Phase 1 Dose Escalation, PK urine samples will be collected predose on Day 1 of Cycle 1 and from 0 
to 12, 12 to 24, and 24 to 48 hours postdose. The 24- to 48-hour postdose sample (QOD) must be collected prior to TAS-120 
administration on Day 3 of Cycle 1. See Section 10.13.2, Pharmacokinetic Urine Sample Collection (QOD Arm Only). 
m Pharmacodynamic Urine Sampling: During Phase 1 Dose Escalation, collect pharmacodynamic urine samples at the following time points 
on Day 1 and the last Wednesday of Cycle 1 (QOD) or on Day 1 and Day 21 of Cycle 1 (QD): predose and from 0 to 12, 12 to 24, and 24 to 
48 hours (QOD arm only) postdose. The 24- to 48-hour postdose sample (QOD) must be collected prior to TAS-120 administration on Day 3 
and the last Friday of Cycle 1. The 12- to 24-hour postdose sample (QD) must be collected prior to TAS-120 administration on Day 2 and 
Day 22 of Cycle 1. See Section 10.13.4, Pharmacodynamic Urine Sample Collection, for detailed description of the pharmacodynamic 
urine sampling schedule. 
n Prior and Concomitant Medications: Collect from the time the ICF is signed through 30 days after administration of the last dose of TAS-
120. 
o Adverse Event Assessment: Collect from the time of the first dose of TAS-120 through 30 days after administration of the last dose of TAS-
120. 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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p Tumor Assessments/Scans for Solid Tumors: Perform the same tumor assessments/scans obtained at Screening at the end of every 2 
cycles (± 7 days) up to Cycle 4. Thereafter tumor assessments and scans may be performed every 3 cycles, or as clinically indicated. See 
Section 10.16.1 , Solid Tumor Assessment/Scans Section 10.16.2 for details. Computed tomography scans obtained before the ICF is 
signed may be used as the screening tumor scan if done within 28 days of the first dose of TAS-120. A CT scan must be performed within 
2 weeks of discontinuation of TAS-120 treatment, if the patient discontinued for reasons other than radiological disease progression. For 
scheduled tumor assessments thereafter, see Section 10.16.1 , Solid Tumor Assessment/Scans, Section 10.16.2 and Section 11.1, Efficacy 
Assessment for Solid Tumors. 
q TAS-120 Treatment: QOD arm: TAS-120 will be administered orally, once daily, in the morning (Phase 1 Dose Escalation only) with a glass 
of water on an empty stomach, 3 times a week (Monday, Wednesday, and Friday) between Days 1 through 21 of each cycle. See Section 
9.1.1, Treatment Regimen, for TAS-120 dose levels. QD arm: TAS-120 will be administered orally, once daily, in the morning (Phase 1 
Dose Escalation only) with a glass of water on an empty stomach, continuously on Days 1 through 21 of each cycle. See Section 9.1.1, 
Treatment Regimen, for TAS 120 dose levels. 
r Tumor Tissue Sampling for PGx Analysis: Previously collected archived tumor tissue samples (PGx samples) from patients with solid tumors 
must be shipped to the central PGx laboratory designated by the sponsor, after patients have provided informed consent. For Phase 1 
Dose Escalation and Phase 1 Expansion, patients can be enrolled before central PGx laboratory confirmation of FGF/FGFR abnormality 
has been obtained; however, if available, the archived PGx tissue sample should be collected and shipped to the central laboratory after 
the signing of the ICF. For Phase 2, refer to the Pharmacogenomic Operation Procedure Manual provided by the sponsor. 
 
 
 
 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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5. 
ENDPOINTS 
This study is to evaluate safety, tolerability, PK, pharmocodynamic, and antitumor 
activity of the TAS-120 in patients with advanced solid tumors. The efficacy, safety, 
pharmacokinetic and other endpoints in the study are listed below. The detailed 
information regarding collections and analysis methods is presented in Sections 9, 10, 
11, and 12. 
5.1. 
SAFETY ENDPOINTS 
5.1.1. 
Adverse Events 
An adverse event (AE) is any untoward medical condition that occurs in a patient while 
participating in this clinical study. Treatment-Emergent AEs (TEAEs) are those AEs that 
occur from the initiation of TAS-120 administration to 30 days after the last dose of 
study medication, and do not necessarily have a causal relationship to the use of the 
study medication. The TEAEs will be summarized. 
5.1.2. 
Laboratory Evaluations 
Safety laboratory test results will be collected. All applicable hematological and 
chemistry laboratory parameters will be graded using computer algorithm per numeric 
ranges defined in the NCI Common Terminology Criteria for Adverse Events (CTCAE), 
v4.03. The related endpoints include the worst severity grade will be summarized. 
5.1.3. 
Vital Signs and Body Weight 
Vital signs (blood pressure, heart rate, body temperature, and respiration rate) and 
body weight will be collected. 
5.1.4. 
ECG 
The 12-lead resting electrocardiogram (ECG) will be performed. ECG findings including 
QT Interval, QTcB, QTcF and RR interval will be recorded and described in Section 10.7. 
5.1.5. 
Physical Examination 
The physical examination will also be performed in the study. 
 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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5.2. 
PHARMACOKINETIC ENDPOINTS 
For Phase 1 Dose Escalation, the PK parameters in blood 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. 
• 
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  
Terminal half-life time 
• 
RCmax 
Accumulation ratio calculated based on Cmax 
• 
RAUC 
Accumulation ratio calculated based on AUC0-last 
 
The following parameters will be calculated on only 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)  
 
5.3. 
PHARMACODYNAMIC ENDPOINTS 
For pharmacodynamics evaluations in blood, serum phosphorus and FGF23 will be 
determined. For the urine pharmacodynamics evaluation, phosphorus and calcium in 
urine will be determined.  
5.4. 
EFFICACY ENDPOINTS 
Tumor measurements using radiological imaging studies will be collected. The 
investigator will evaluate the imaging studies for tumor response and/or progression. 
Response assessment will be made based on the Response Evaluation Criteria in Solid 
Tumors (RECIST) criteria (version 1.1, 2009).   
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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The efficacy endpoints in the study are Best Overall Response, overall response rate 
(ORR), disease control rate (DCR), and duration of response (DR). In addition, time to 
radiological progression and/or progression-free survival may be explored as 
appropriate. 
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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6. 
ANALYSIS SETS 
The study populations include safety, DLT-evaluable, PK, pharmacodynamic, and 
efficacy populations. 
6.1. 
SAFETY POPULATION 
The safety population will include all patients who received at least 1 dose of TAS-120. 
This population will be the basis for safety evaluation. 
6.2. 
DLT EVALUABLE POPULATION  
The DLT evaluable population will include all patients in Phase 1 Dose Escalation who 
either experience a DLT during the first cycle of treatment or who complete the first 
cycle of with at least 80% of planned study medication (TAS-120) administered.  MTD 
determination will be based on this population. 
 
6.3. 
PK AND PHARMACODYNAMIC POPULATION  
The PK and pharmacodynamic population in Phase 1 Dose Escalation 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. 
6.4. 
EFFICACY POPULATION 
The efficacy population will include all patients in the safety population.  
6.5. 
PROTOCOL DEVIATIONS 
The protocol deviations may include: informed consent errors, not meeting an eligibility 
criterion, study drug overdose or other incompliance. The details will be included in 
TPU-TAS-120-101 Protocol Deviation Definition Document. The major protocol 
deviations may be summarized while the minor protocol deviations will only be listed.  
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 31 of 64 
7. 
GENERAL ASPECTS FOR STATISTICAL ANALYSIS 
7.1. 
GENERAL METHODS 
All relevant data will be presented in patient data listings. 
All categorical (binary and ordinal) data will be summarized using frequency counts and 
percentages of patients. Percentage will be calculated using the corresponding 
treatment group in the study population as the denominator. The continuous variables 
will be summarized using number of non-missing observation (n), mean, standard 
deviation (SD), median, minimum and maximum unless otherwise specified. For 
example, the numbers of events and censorings will be reported for time-to-event 
analysis. All estimations will include a point estimate and the corresponding 95% 
confidence interval.    
Summary tables will be presented by dosing schedule (i.e., QOD and QD), dose level and 
overall. Data listings will be ordered by assigned dosing schedule, dose level and patient 
ID. The dose levels presented in tables and listings for Phase 1 Dose Escalation are: 
8 mg QOD, 16 mg QOD, 24 mg QOD, 36 mg QOD, 56 mg QOD, 80 mg QOD, 120 mg QOD, 
160 mg QOD, 200 mg QOD, 240 mg QOD; 
 
4 mg QD, 8 mg QD, 16 mg QD, 20 mg QD, 24 mg QD, 36 mg QD, 56 mg QD, 80 mg QD, 
120 mg QD, 160 mg QD, 200 mg QD, and 240 mg QD if applicable. 
 
For concomitant medications and adverse events, the cycles are determined based on 
their start/onset dates. For other collected data, the cycles are determined based on 
their visit dates.  
When there are multiple laboratory records for a scheduled visit, the one closest to the 
target date (relative to the Day 1 in that cycle) will be used for analysis. If there are 
two or more records with the same time period to the target date, the later one will be 
used for analysis. However, the baseline for laboratory test is the defined as the latest 
laboratory result prior to the first dose of study medication.    
All the analyses of safety, efficacy and pharmacodynamics data for this study will be 
performed using SAS® statistical software package, Version 9.3 or a later version. 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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7.2. 
KEY DEFINITIONS 
7.2.1. 
First Dose Date 
First dose date in the study is defined as the first dose of TAS-120 in Cycle 1. 
7.2.2. 
Cut-Off Date of Final Analysis 
For the purpose of final analysis, the cut-off date is defined as the date which all 
patients either discontinue from the treatment or have sufficient follow-up (more than 
6 months) from the date of the first day of treatment with TAS-120 of the last patient 
enrolled, whichever occurs first. 
7.2.3. 
Last Dose Date 
For the purpose of analysis, the last dose date is defined as the last dose date of TAS-
120 for the patient or the cut-off date of final analysis, whichever occurs first. 
7.2.4. 
Study Day 
The study day in the study is the days relative to the first dose date in the study, while 
the cycle day is the days relative to the first dose date in that cycle. 
7.2.5. 
Treatment Duration 
The overall treatment duration is defined as last dose date – first dose date+1. 
7.3. 
MISSING DATA 
Missing data will not be imputed.  Complete missing or partial date will be presented in 
the listings as reported on CRFs.  
If an AE has a completely missing onset date, then the AE will be considered a TEAE. A 
medication with a completely missing start date is considered a prior medication. A 
medication with a completely missing stop date is considered a concomitant 
medication.  
If an adverse event or a medication has a partial missing start or stop date, the 
following rules will be used to determine whether it is an AE or a TEAE, or a prior or 
concomitant medication.  
 
 
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Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 33 of 64 
Table 4: Partial Date Imputation for TEAE Determination 
Partial Missing Start or 
Stop Date 
 
Derived Start Date 
Imputed Stop Date 
Missing month and day, 
and the year  is present 
 
January 1 of that year or first 
dose date if the year is the same 
as the year of  first dose date 
 
December 31 of that 
year 
Missing day, but year and 
month are present 
 
First day of that month or first 
dose date if the year and month 
are the same as the year and 
month of first dose date 
 
Last day of that month 
Missing month, but year 
and day are present 
Missing 
month 
derived 
as 
January or same as first dose 
month if the year is same as the 
year of first dose.  
 
Missing month imputed 
as December 
 
The above rule is also used for determining the cycles of adverse events and 
concomitant medications.  
 
The derived date is only used for determining TEAEs, cycle of adverse events and 
concomitant medications.  The collected partial dates will be reported in the listings.    
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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8. 
DEMOGRAPHIC, OTHER BASELINE CHARACTERISTICS AND 
MEDICATION 
8.1. 
SUBJECT DISPOSITION AND WITHDRAWALS 
The number of patients in each study population will be summarized along with the 
reason for exclusion from the population.  In addition, patients’ status with regard to 
study treatment and follow-up will also be summarized, along with the reasons for study 
discontinuations. 
8.2. 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Demographics and baseline characteristics (age, gender, ethnicity, race, weight, and 
height) will be summarized by dose level and overall for Phase 1 Dose Escalation. 
8.3. 
MEDICAL HISTORY 
Medical history will be coded according to the Medical Dictionary for Regulatory 
Activities (MedDRA 17.0).  Medical history will be listed by dose level or disease type, 
patient number, start date and end date. There is no imputation for dates for medical 
history. 
8.4. 
OTHER BASELINE DISEASE CHARACTERISTICS 
The cancer type (NSCLC, breast cancer, gastric cancer and other solid tumor), 
FGF/FGFR status (FGFR1 amplification, FGF19 amplification etc) by local genotyping 
assay) will be summarized by dose level and overall by dosing schedule .   
Pre-study surgery and prior radiation therapy will be summarized by dose level and 
overall by dosing schedule. For pre-study surgery, the number and percentage of 
patients with biopsy, primary tumor removal, metastatic tumor removal, and other 
surgeries will be reported. For prior-radiation therapy, the number and percentage of 
patients with palliative and therapeutic radiation therapies will be presented in the 
summary table. 
All prior anticancer therapies (adjuvant therapies, neoadjuvant therapies, therapies for  
advanced/metastatic disease, and maintenance therapies including prior FGFR 
inhibitor) will be summarized by dose level  and overall by dosing schedule. The number 
of patients with 1, 2, 3 and >=4 prior regimens will be summarized for all anticancer 
therapies and for advanced/metastatic disease only.    
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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Page 35 of 64 
All collected information for cancer diagnosis, pre-study surgery, prior-radiation 
therapy, and prior anti-cancer therapy will also be listed. 
8.5. 
MEDICATION 
Prior or concomitant medications will be collected from the time of informed consent 
through 30 days after administration of last dose of study medication.  
Medications which started and stopped prior to the first dose of TAS-120 are considered 
as prior medications. Medications which started prior to the first dose of TAS-120 and 
continued into the treatment period are considered as prior and concomitant 
medications.  
Medications with a start date from first dose of TAS-120 to 30 days after administration 
of the last dose of TAS-120 will be considered as concomitant medications.  
Prior and concomitant medications will be coded according to World Health 
Organization (WHO) Drug Dictionary (WHODrug version March 2014) for Concomitant 
Medication. The concomitant medications will be summarized by ATC level 2 
(Therapeutic Main Group) and ATC level 4 (Chemical/Therapeutic Subgroup) using the 
number and percentage of patients by dose level and overall. Medications will be sorted 
in descending order of frequency of ATC level 2 and ATC level 4 within ATC level 2 in 
the total column. A patient will be counted only once within each level of summation if 
the patient has taken a medication more than once. 
All prior and concomitant medications will be listed. 
 
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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9. 
EFFICACY 
Solid Tumor Assessments 
Tumor assessments/imaging studies of the chest, abdomen, and pelvis (as clinically 
indicated) will 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 (± 7 days), up to Cycle 4. 
• 
Following Cycle 4, at least after every 3 cycles or as clinically indicated. 
• 
Within 2 weeks after 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 for 
target lesions, non-target lesions and overall responses are provided in the following 
Tables 5, 6, 7 and 8.  
Table 5:  Assessments for Target Lesions 
TARGET LESIONS 
Lesion Response: 
Definition: 
Complete Response (CR) 
The disappearance of all target lesions. Any pathological lymph 
nodes must have reduction in short axis to < 10 mm. 
Partial Response (PR) 
At least a 30% decrease in the sum of diameters of the target 
lesions, taking as a reference the baseline sum diameters. 
Progressive Disease (PD) 
At least a 20% increase in the sum of diameters of the target 
lesions, taking as a reference the smallest sum on study, 
including the baseline sum. In addition to the relative increase 
of 20%, the sum must also demonstrate an absolute increase of 
at least 5 mm. Definitive new lesion presence also indicates 
progression. 
Stable Disease (SD) 
Neither sufficient shrinkage to qualify for PR nor sufficient 
increase to qualify for PD, taking as a reference the smallest 
sum diameters while on study. 
 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
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Table 6:  Assessments for Non-Target Lesions 
NON-TARGET LESIONS 
Lesion Response: 
Definition: 
Complete Response (CR) 
Disappearance of all non-target lesions and normalization of 
tumor marker level. All lymph nodes must be non-pathological 
in size (< 10-mm short axis) 
Non-CR/Non-PD 
Persistence of one or more non-target lesion(s) and/or 
maintenance of tumor marker level above the normal limits. 
Progressive Disease (PD) 
Unequivocal progression of existing non-target lesions (see 
definition below).  
 
Table 7: Overall Response Assessment with Target Lesions 
Target Lesions 
Non-target Lesions 
New Lesions 
Overall 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 
 
Table 8: Overall Response Assessment without Target Lesions 
Non-target Lesions 
New Lesions 
Overall 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 
 
For Phase 1 Dose Escalation, only on-site tumor assessments will be conducted.  
 
9.1. 
BEST OVERALL RESPONSE 
The best overall response is the best response recorded from the start of treatment 
until progressive disease or the start of subsequent anticancer treatment.  
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Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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For patients with solid tumors, according to RECIST guideline (Version 1.1, 2009), to be 
assigned a status of PR or CR, changes in tumor measurements in patients with 
responding tumors must be confirmed at least 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.  
At the analysis stage, the best overall response will be assigned for each patient as the 
best response recorded from all time point responses recorded from the start of 
treatment. Confirmation of partial response and complete response will follow the 
confirmation process contained in the following table where the best two consecutive 
time points are considered. Best overall response both with confirmation of partial 
response and complete response and without confirmation of partial response and 
complete response will be summarized. 
Earlier Response 
(not yet confirmed) 
Later Response 
(confirmation) 
Confirmed Response  
Complete Response 
Complete Response 
Complete Response 
Complete Response 
No Complete Response or 
missing 
Stable Disease 
Partial Response 
Complete Response or Partial 
Response  
Partial Response 
Partial Response 
Stable Disease or Progressive 
Disease  or missing 
Stable Disease 
Partial Response  
Stable disease and then partial 
response (only one SD in 
between) 
Partial Response 
Stable Disease 
n/a – no confirmation needed  
Stable Disease 
Progressive Disease 
n/a – no confirmation needed  
Progressive Disease 
 
  
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
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9.2. 
OBJECTIVE RESPONSE RATE 
The objective response rate (ORR) is defined as the proportion of patients who achieved 
best overall response of ≥ partial response (PR) in the Efficacy Population (CR or PR for 
solid tumor patients. ORR based on the Investigator’s assessments will be summarized 
by disease type (for example NSCLC with FGFR1 amplification, breast cancer with 
FGFR1 amplification, gastric cancer with FGFR2 amplification, and other solid tumors 
with other alternative FGF/FGFR abnormality) by dosing schedule and overall. The 
corresponding 90% and 95% confidence intervals will be presented.  
9.3. 
DURATION OF RESPONSE 
Duration of response 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 progressive disease (PD) or death due 
to any cause.  
After the first documentation of response, patients who are alive and progression free 
during the treatment period and follow-up will have their event time censored on the 
last tumor assessment date in the study treatment. For the purpose of final analyses for 
dose escalation phase, the last assessment date should be prior to the cut-off date of 
final analysis for which all patients either discontinue from the treatment or have 
sufficient follow-up (more than 6 months) from the date of the first day of treatment 
with TAS-120 of the last patient enrolled, whichever occurs first. For patients who start 
another anticancer treatment, their events should be censored at the last tumor 
assessment prior to the new treatment.    
Time to response and Duration of response will be listed for Efficacy Population for 
Phase 1 Dose Escalation.  
   
 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
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10. 
SAFETY 
The population used for safety analyses will be the Safety Population.  Safety will be 
assessed on the basis of adverse event (AE) reports, clinical laboratory data, ECG 
parameters, physical examinations, vital signs and body weight, performance status, 
ophthalmological examination, and neurological examination. 
10.1. EXTENT OF EXPOSURE 
The actual dosage in the study for TAS-120 will be calculated for capsules and dosage. 
Since the patients may have different treatment periods, the average daily dose is 
defined as the dosage divided by actual dose duration, which is the sum of all cycle 
treatment period prior to the cut-off date of final analysis. 
The cycles initiated and completed, extent of exposure (treatment duration), and total 
dosage for TAS-120 will be summarized by dose level and overall for Phase 1 Dose 
Escalation by dosing schedule.  
Relative dose intensity (RDI) is defined as the ratio of the amount of drug actually 
administered to the amount planned in the study for TAS-120. The relative dose 
intensity from Day 1 of Cycle 1 is calculated in the following steps: 
1. For each cycle, calculate the actual total dose administered in mg for TAS-
120.  
 
2. The total dose administered in mg is the sum of all cycle total doses 
administered in mg in the study. 
 
3. Total treatment duration in weeks for dose intensity calculation = (last dose 
date – first dose date +1) for QD; or (last dose date – first dose date +2) for 
QOD . 
 
4. Weekly Dose Intensity = Total dose administered in mg divided by total 
treatment duration in weeks. 
 
5. Relative Dose Intensity = Weekly Dose Intensity divided by the planned 
weekly dose in mg, which is the planned dose level in mg/day multiplied by 
3.5 for QOD and multiplied by 7 for QD.  The Relative Dose Intensity will be 
expressed in percentage. 
 
Relative dose intensity will be summarized by dose levels and dosing schedule for cycle 
1 and for all cycles.  
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
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In addition, patients with TAS-120 dose reductions from the previous cycle, patients 
with dose reductions due to AEs, patients with dose held/delays due to AEs, and 
patients with treatment discontinuations due to AEs will be summarized for the entire 
study.  
All recorded information for study medication administration and accountability for 
TAS-120 will be listed. 
10.2. DOSE LIMITING TOXICITY  
The dose limiting toxicity in the first cycle of Phase 1 Dose Escalation will be presented 
by dose level and overall for Safety Population by dosing schedule. The compliance to 
the 3+3 design scheme for dose escalation rules will be shown in the table.  
10.3. ADVERSE EVENTS 
An adverse event (AE) is any untoward medical condition that occurs in a patient while 
participating in this clinical study. 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, v4.03, where applicable.   
 
Treatment-Emergent Adverse Events (TEAEs) are those adverse events that occur from 
the initiation of TAS-120 medication administration to 30 days after the last dose of 
study medication, and do not necessarily have a causal relationship to the use of the 
study medication. Treatment-Emergent Adverse Events (simply referred to as adverse 
events in summary tables) will be summarized.  
A Serious Adverse Event (SAE) is an AE which falls into one or more of the following 
categories: 
a. Results in death 
b. Is life-threatening 
c. Requires inpatient hospitalization or prolongation of existing hospitalization   
d. Results in persistent or significant disability or incapacity  
e. Is a congenital anomaly/birth defect  
f. Is any other important medical event  
All deaths occurring through the 30-day follow-up period is reported as outcomes of 
SAEs. Signs, symptoms and complications related to disease progression should be 
reported as AE or SAEs. Clinical disease progression may only be reported as an SAE 
term if none of the relevant signs or symptoms supports a fatal outcome. While those 
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
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severe AEs are classified into Grade 3 AEs, those life-threatening AEs are classified into 
Grade 4 AEs. 
Adverse Events will be summarized by dose level and overall for Phase 1 Dose 
Escalation. AEs will be presented by system organ class in the overall column in 
decreasing order. Within each system organ class, the AEs will be displayed by preferred 
term (PT) in decreasing order in the overall column.  
The following adverse event summary tables will be generated: 
1) An overall summary with the number and percentage of patients reporting AEs, 
serious AEs, grade 3 or higher AEs, treatment-related AEs, Dose Limiting 
Toxicities, AEs leading to study treatment (TAS-120) discontinuation and AEs 
with outcome of deaths. Summary with combined groups will also be generated.  
2) AEs overall and by system organ class and preferred term.  
In the summary, a patient is counted once at the system organ class and once at 
each preferred term within the system organ class. Additional summary by 
system organ class, preferred term and grade (including Total and >= grade 3 
categories) will also be generated. 
3) Study-treatment-related AEs overall and by system organ class and preferred 
term. Additional summary by system organ class, preferred term and grade 
(including Total and >= grade 3 categories) will also be generated. 
All those AEs with relationship to TAS-120 marked as “Related” or missing will be 
reported in the table.  
4) AEs by highest grade (worse severity) overall and by system organ class and 
preferred term.  
In the summary, a patient is counted once at the highest grade for which the 
event occurred in the system organ class and the highest grade for each unique 
preferred term within that system organ class. Therefore, patients may only 
contribute once to each preferred term and once to each system organ class. 
The missing severity grade will be reported in a separate category. 
5) Serious AEs, overall and by system organ class and preferred term. Additional 
summary by system organ class, preferred term and grade (including Total and 
>= grade 3 categories) will also be generated. 
6) Grade 3 or higher AEs, overall and by system organ class and preferred term 
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Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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7) Study-treatment related AEs by grade (severity) , overall and by system organ 
class and preferred term 
8) AEs leading to study treatment termination, overall and by system organ class 
and preferred term. Additional summary by system organ class, preferred term 
and grade (including Total and >= grade 3 categories) will also be generated. 
9) AEs with outcome of deaths, overall and by system organ class and preferred 
term  
In addition, the time to onset of some special AEs of interest in the study may be 
summarized if appropriate.   
Dose limiting toxicity list will be provided based on the DLT evaluable population. 
10.4. LABORATORY EVALUATIONS 
Blood samples for hematology, coagulation and serum chemistry assessments are 
collected and measured at baseline (within 7 days prior to study medication 
administration on Day 1 of Cycle 1), within 24 hours prior to Day 1 study drug 
administration of each cycle, anytime on Day 8 and Day 15 of Cycle 1 and Cycle 2, the 
end of treatment visit and 30-day safety follow-up visit. Starting with Cycle 3, the Day 8 
assessment is not required, unless deemed clinically indicated by the investigator. 
Creatine kinase needs to be repeated on Day 1 of Cycle 2. Fractionation of CK into its 
isoforms must be performed in case of an elevation of CK (unless the isoform CK 
[isoform skeletal and heart muscle] [CK-MM and CK-MB] was tested, in which case a 
fractionation is no longer needed). If CK is abnormally elevated at Screening (Day -7 to -
1), the results of the fractionation must be available prior to starting TAS-120 treatment 
for that patient. 
Hematology and coagulation parameters that will be measured include: RBC count, 
Hemoglobin, Hematocrit, Platelets, INR, APTT, White blood cell (WBC) count with 
differential, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils. Serum 
chemistry parameters that will be measured include: ALT (SGPT), AST (SGOT), Alkaline 
phosphatase, Total bilirubin, Albumin, Creatinine, Blood urea nitrogen (BUN), 
Phosphorus, Calcium, Chloride, Sodium, Potassium, Bicarbonate, Glucose, CK, and CRP 
and ß2-microglobulin for multiple myeloma only. Fractionation of bilirubin 
(direct/indirect bilirubin or conjugated/unconjugated) must be performed in case of an 
elevation of total bilirubin. 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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Urine sample for qualitative analysis are only collected at baseline (within 7 days prior 
to study medication administration on Day 1 of Cycle 1), within 24 hours prior to study 
medication administration on Day 1 beginning with Cycle 2, the end of treatment visit  
and 30-day safety follow-up visit. The following parameters will be measured: protein, 
glucose, and urine density. 
The website http://www.globalrph.com/conv_si.htm provides conversion factors 
between SI units and Conversion units. 
The CTCAE grades of Hemoglobin, Platelet, INR, APTT, White blood cell (WBC) count 
with differential, Neutrophils, Lymphocytes, Fibrinogen, ALT (SGPT), AST (SGOT), 
Alkaline phosphatase, Bilirubin, Albumin, Creatinine, Calcium, Sodium, Potassium, and 
Glucose will be determined using computer algorithm only based on the numerical 
component of CTCAE v4.03 grading scale. For the parameters with uni-directional 
criteria, the CTCAE grade will be derived from 0 to 4. For the parameters with bi-
directional criteria, the CTCAE grade will be derived from both low and high direction. 
Grade 0 is defined for a non-missing value which doesn't meet any criteria and within 
the normal range. 
  
The worst severity grade during the treatment and 30 days follow-up will also be 
summarized descriptively. For the parameter with bi-directional criteria, both highest 
and lowest grade will be summarized. The worst grade in cycle 1 also will also be 
summarized in same way. 
The shift in CTCAE grades from baseline to the worst grade in Cycle 1, and Entire Study 
for bi-directional parameters and unidirectional parameters will be presented. For all 
lab tests, a shift table in normal range from baseline to the worst grade in Cycle 1, and 
Entire Study will also be presented.   
All collected laboratory hematology, coagulation, serum chemistry and urinalysis results 
will be listed. The normal laboratory ranges provided by laboratory will be also listed. 
10.5. VITAL SIGNS AND BODY WEIGHT 
Vital signs (blood pressure, heart rate, body temperature, and respiration rate) and 
body weight are collected at baseline (within 7 days prior to study medication 
administration on Day 1 of Cycle 1), within 24 hours prior to study drug administration 
on Day 1 beginning with Cycle 2, the end of treatment visit and 30-day safety follow-up 
visit. 
The observed values of vital sign and weight and their changes from baseline at these 
scheduled visits will be summarized descriptively by cohort and overall. When the 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
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multiple results recorded at the same visit, the last valid result will be used for the 
summary. All values for vital sign and weight collected on eCRFs will be listed.  
10.6. ECG  
The 12-lead resting electrocardiogram (ECG) are performed at screening (within 28 days 
prior to the study medication administration on Day 1 of Cycle 1), 2 hours after the dose 
on Day 1 of Cycle 1 and the last Wednesday of Cycle 1 (QOD arm) or 2 hours after study 
medication administration on Day 1 and Day 21 of Cycle 1 (QD arm) for patients enrolled 
in Phase 1 Dose Escalation, and the end of treatment visit and 30-day follow-up visit. 
For UK Protocol version, the 12-lead resting ECG is also performed at Day 1 ± 3 days 
beginning with Cycle 3 (Phase 1 Dose Escalation).  
A summary table reported the counts and percentage of Normal and Abnormal (CS, NCS) 
ECG will be presented for safety population and UK safety subgroup.  
For QT Interval, and its Fridericia’s correction, the absolute QT/QTc interval 
prolongation are defined in three different ways as: (1) QT (QTc) interval>450 ms; (2) 
QT (QTc) interval>480 ms; (3) QT (QTc) interval>500 ms. The change from baseline in 
QT (QTc) interval are defined in two different categories as: (1) QT(QTc) interval 
increases from baseline >30 ms;  (2)  QT(QTc) interval increases from baseline >60 ms. 
The number and percentage of patients meeting the above different categories will be 
summarized by dose level and overall for safety population and UK safety subgroup. A 
graph for QT interval and its Fridericia’s correction may also be presented.      
10.7. PHYSICAL EXAMINATION 
Physical examination are performed at baseline (within 7 days prior to study medication 
administration on Day 1 of Cycle 1), within 24 hours prior to study drug administration 
on Day 1 beginning with cycle 2, the end of treatment visit and 30-day safety follow-up 
visit. The physical examination data is presented in a data listing. 
10.8. PERFORMANCE STATUS 
ECOG performance status is recorded at baseline (within 28 days prior to study 
medication administration on Day 1 of Cycle 1), Day 1 of cycle 1 prior to first dose, 
within 24 hours prior to study drug administration on Day 1 beginning with Cycle 2, the 
end of treatment visit and 30-day safety follow-up visit. 
ECOG Performance Status scores have 6 different grades from 0 to 5 and described in 
the following table: 
Table 10: Eastern Cooperative Oncology Group 
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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GRADE 
ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, eg, light house work, office work. 
2 
Ambulatory and capable of all self-care but unable to carry out any work 
activities.  Up and about more than 50% of waking hours. 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of 
waking hours. 
4 
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or 
chair. 
5 
Dead. 
The change from Day 1 in Cycle 1 in the ECOG Performance Status scores will be 
presented in a shift table by cohort and overall. 
10.9. OPHTHALMOLOGICAL EXAMINATION 
Ophthalmological examination will be performed at baseline (within 28 days prior to 
study medication administration on Day 1 of Cycle 1) and 4-6 weeks after the first dose. 
The examination will be repeated, if clinically indicated, and the repeat examination 
will include the same testing employed at baseline in addition to any other clinically 
indicated examination. Ophthalmological examination result will be listed. 
10.10. NEUROLOGICAL EXAMINATION 
Neurological examination will be performed at baseline (within 28 days prior to study 
medication administration on Day 1 of Cycle 1). The basic neurologic examination 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 baseline in addition to any other clinically indicated examination. 
Neurological examination result will be listed.  
10.11. PREGNANCY TEST 
If the patient is female and of child bearing potential, a serum or urine β-HCG 
pregnancy test will be performed 7 days prior to the first administration of the study 
drug. Pregnancy test result will be listed. 
 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
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11. 
PHARMACOKINETICS 
INC Research Biostatics Group is responsible for the calculation of pharmacokinetic 
parameters statistical analysis, production and quality control of TLFs of the PK data. 
11.1. SAMPLE COLLECTION 
During Phase 1 Dose Escalation, blood samples for pharmacokinetic analysis will be 
collected at the following time points on Day 1 of Cycle 1 (C1D1) and on the last 
Wednesday of Cycle 1 (C1LW) (QOD arm) or on Day 1 of Cycle 1 (C1D1) and Day 21 of 
Cycle 1 (C1D21) (QD arm):  
pre-dose (-0.5hr) and after the morning dose at 0.5 hr (± 0.1 hr), 1 hr (± 0.1 hr), 2 hr (± 
0.2 hr), 3 hr (± 0.2 hr), 4 hr (± 0.5 hr), 6 hr (± 0.5 hr), 8 hr (± 0.5 hr), 12 hr (± 2 hr), 24 
hr (± 2 hr) (QOD and QD arms), and 48 hr (± 2 hr) (QOD only). 
The 48-hour postdose sample (QOD arm) and the 24-hour postdose sample (QD arm) 
must be collected prior to TAS-120 administration on that day. 
During Phase 1 Dose Escalation, urine samples for pharmacokinetic analysis of TAS-120 
will be collected on Day 1 of Cycle 1 (QOD arm) at the following time points:  
pre-dose, 0 to 12 hr (±2 hr), 12 to 24 hr (±2 hr), and 24 to 48 hr (±2 hr).  
The 24 to 48 hours postdose sample must be collected prior to TAS-120 administration 
on Day 3 and the last Friday of Cycle 1. 
11.2. 
PK PARAMETERS TO BE CALCULATED 
The following PK parameters will be calculated for Day 1 of Cycle 1 (C1D1) and the last 
Wednesday of Cycle 1 (C1LW) in QOD arm, and for C1D1 and Day 21 of Cycle 1 (C1D21), 
according to the non-compartment method. AUC0-inf, MRT, CL/F and Vd/F will be 
calculated only for C1D1. Urine PK parameter will be calculated for only C1D1 in QOD 
arm. The calculated PK parameters will be summarized by study arm, dose levels and 
study periods. 
Plasma PK parameters: 
• 
Cmax (ng/mL):   
Maximum concentration in plasma 
• 
Tmax (hr):  
 
Time to reach maximum concentration in plasma 
• 
AUC0-last (ng∙hr/mL):  Area under the concentration-time curve up to the last 
observable concentration  
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Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
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• 
AUC0-inf (ng∙hr/mL):  Area under the concentration-time curve up to infinity on 
C1D1 calculated as follows: 
AUC0-inf = AUC0-last + Clast/λz 
where Clast is the last measurable plasma concentration and λz is the elimination 
rate constant after the AM dose estimated using log-linear regression during the 
elimination phase. The points used in the λz calculation will be determined by 
visual inspection of the data describing the elimination phase and at least three 
time points will be used in λz calculations. 
• 
AUC0-24 (ng∙hr/mL):  Area under the concentration-time curve up to 24 hours 
estimated as partial area (QD arm) 
• 
AUC0-48 (ng∙hr/mL):  Area under the concentration-time curve up to 48 hours 
estimated as partial area (QOD arm) 
• 
T1/2 (hr):  
 
Terminal half-life time = ln(2)/ λz 
• 
MRT (hr): 
 
Mean residence time = AUMC0-inf/AUC0-inf 
where AUMC0-inf is the area under the first moment curve (AUMC) extrapolated to 
infinity. 
• 
CL/F (L/hr):  
Oral clearance = Dose/AUC0-inf 
where the dose will be the actual dose per body of TAS-120. 
• 
Vd/F (L): 
 
Apparent volume of distribution = (CL/F)/λz 
• 
RCmax:  
 
Accumulation ratio calculated based on Cmax 
= Cmax (C1LW or C1D21)/ Cmax (C1D1) 
• 
RAUC: 
 
 
Accumulation ratio calculated based on AUC0-last 
= AUC0-last (C1LW or C1D21)/AUC0-last (C1D1) 
 
Urine PK parameters: 
• 
Ae% (%): 
 
Urinary excretion rate as % of dose = Ae(total amount of 
excretion)/dose 
• 
CLr (mL/min):  
Renal clearance = Ae(total amount of excretion)/AUC0-48 
 
11.3. 
PLASMA AND URINE CONCENTRATION DATA 
Plasma and urine concentration data will be assayed at Covance Laboratories Inc. as per 
the sample analysis outline of the bioanalytical study below. 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
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11.4. 
PK SAMPLE COLLECTION TIME 
The calculation of PK parameter in plasma will be based on the actual time after the 
dosing. The values will be calculated as “actual clock time of blood collection” – 
“actual clock time of dosing” to obtain actual hours after dose.  The actual time after 
dose will be summarized by study arm, dose levels and study periods according to 
nominal collection time. The urine PK parameters will be summarized according to 
nominal collection period, without any corrections with actual sampling time. The 
concentration data out of the time window will not be excluded from analysis unless the 
time point is overlapped with adjacent time points. 
11.5. 
CALCULATION OF PLASMA PK PARAMETERS 
Estimation of pharmacokinetic parameters in plasma will be performed using Phoenix™ 
WinNonlin® (Certara, L.P.), Version 6.4 or later software. 
The PK parameters of interest are Cmax, Tmax, AUC0-last, AUC0-inf (C1D1 only), AUC0-24, T1/2, 
MRT (C1D1 only), RCmax, RAUC, CL/F (C1D1 only), and Vd/F (C1D1 only). The Cmax and Tmax 
are obtained from experimental observations. If the maximum plasma concentration 
occurs at 2 or more time points, the Tmax is assigned to the time of the earliest 
occurrence. In determining the Tmax, the actual time of the plasma sample relative to 
the dosing time will be used.  
The BLQ value will be handled as follows for the calculation of plasma PK parameters:  
• 
The time of collection of the pre-dose sample will be set to zero; 
• 
Actual post-dose sampling times are expressed relative to the time of dosing; 
• 
Plasma concentrations below the LLOQ in the pre-dose sample(s) and in early 
time-points (lag-time) will be treated as zero, if applicable; 
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 50 of 64 
• 
Plasma concentrations below the LLOQ appearing in terminal samples will be 
treated as missing values;  
• 
Plasma concentrations below the LLOQ in the middle of the curve that are 
flanked by measurable concentrations will be treated as missing values. 
 
At the first dosing (C1D1), if the predose concentration is ≤ 5 percent of Cmax value in 
that subject, the subject’s data without any adjustments can be included in all 
pharmacokinetic measurements and calculations.  If the predose value is > than 5 
percent of Cmax, the subject will be dropped from all PK evaluations. 
The AUCs are calculated using noncompartmental analysis.  The actual time of the 
plasma sample relative to the dosing time is used to calculate the AUCs.  In calculating 
the AUCs a linear trapezoidal method is used for all portions of the plasma 
concentration-time curve.  The AUC0-inf is calculated as the AUC0-last + Clast/λz where 
AUC0-last is the area under the curve from 0 to the last quantifiable concentration, Clast is 
the last quantifiable concentration observed and λz is the absolute value of the slope of 
the terminal log-linear phase. 
The λZ will be calculated using the log-linear regression. Visual inspection and 
improvement in the adjusted RSQ will be used to determine those time points prior up 
to but not including the Cmax. The elimination half-life (T1/2) is calculated as ln(2)/ λz.  
The parameter estimates for T1/2, AUC0-inf, MRT, CL/F and Vd/F will not be calculated if 
ANY of the following conditions are met:  
• 
Insufficient number of time points (less than 3) are available for calculating the 
slope of the log-linear regression line 
• 
The adjusted RSQ is less than 0.81 
• 
The percent of area extrapolated (time of last quantifiable plasma concentration 
to infinity) accounts for more than 20% of the AUC0-inf (AUC0-last / AUC0-inf is less than 
0.80). 
11.6. 
CALCULATION OF URINE PK PARAMETERS 
The urine PK parameters will be determined for TAS-120 on C1D1. The amount of TAS-
120 excreted in each urine collection will be calculated by multiplying the volume (in 
mL) by the concentration. Total amount of urinary excretion from time zero to 48 hours 
postdose (Ae mg) for TAS-120 will be calculated by summing the excretion values over 
all urine collections following a dose of study drug. Urinary excretion will be reported as 
a percentage of the administered dose of study drug (Ae%). 
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 51 of 64 
Renal clearance of TAS-120 will be calculated as below. 
• 
CLr (Renal clearance) = Ae(Total amount of excretion)/AUC0-48 × 106 × 60 
The urine volume, urinary concentration, Ae (mg) Ae% and CLr of TAS-120 will be 
summarized by study arm and dose levels according each urine collection period. 
11.7. PK PARAMETERS SUMMARIZATION 
Individual plasma concentrations will be listed and summarized by dose level and 
collection timepoint/ schedule, including number of observations (N), arithmetic mean, 
SD, CV, minimum, median, and maximum.  
Individual PK parameters will be listed and summarized by dose level and collection 
timepoint/ schedule, including N, arithmetic mean, SD, CV, minimum, median, and 
maximum.  
 
11.8. 
DOSE PROPORTIONALITY 
Dose-proportionality of TAS-120 will be evaluated based on linear, power regression 
analyses, and one-way analysis of variance (ANOVA). 
Regression analysis using linear model 
Dose proportionality of TAS-120 PK parameters (Cmax, AUC0-inf and AUC0-last) will be 
analyzed by regression analysis for both single dose (C1D1) and multiple doses (C1LW or 
C1D21) , Cmax and AUC0-last using linear model as below. 
(AUC or Cmax) = a×(dose)+ b 
This model will be used to investigate the null hypothesis (H0: b=0) with calculating 90% 
confidence intervals for the intercept (b). 
Regression analysis using power model 
Dose proportionality of TAS-120 PK parameters (Cmax, AUC0-inf and AUC0-last) will be 
analyzed by regression analysis for both single dose (C1D1) and multiple doses (C1LW or 
C1D21, Cmax and AUC0-last) using power model as below. 
log(AUC or Cmax) = α+ ß log(dose) 
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 52 of 64 
This model will be used to investigate the null hypothesis (H0: ß=1) with calculating 90% 
confidence intervals for the power constant (ß). 
One-way ANOVA 
Prior to the analysis, dose-dependent parameters (Cmax, AUC0-inf and AUC0-last) will be 
normalized with dose. All PK parameters will be log-transformed prior to the analysis, 
and then the differences in the means of dose levels will be tested by one-way ANOVA. 
11.9. 
ACCUMULATION RATIO 
Besides the calculation of individual accumulation ratio, the mean accumulation ratio at 
RP2D or MTD will be estimated by paired t-test. TAS-120 PK parameters (Cmax, and AUC0-
last) will be log-transformed and the mean ratio will be estimated for C1LW (C1LW/C1D1) 
and C1D21 (C1D21/C1D1). 
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 53 of 64 
12. 
PHARMACODYNAMICS  
A secondary objective of Phase 1 Dose Escalation in this study is to investigate the 
clinical pharmacodynamics of TAS-120. 
12.1. PD ENDPOINTS 
For pharmacodynamics evaluations in blood, serum phosphorus and FGF23 will be 
collected. For the urine pharmacodynamics evaluation, phosphorus and calcium in urine 
will be collected. Urine creatinine levels will also be analyzed as controls and 
phosphorus and calcium level will be normalized by creatinine concentration. 
Exploratory statistical analyses may be performed as appropriate.   
12.2. SAMPLE COLLECTION 
During Phase 1 Dose Escalation, blood samples for pharmacodynamic analysis will be 
collected at the following time points on C1D1 and on C1LW (QOD arm) or on C1D1 and 
C1D21 (QD arm):  
pre-dose (-0.5hr) and after the morning dose at 0.5 hr (± 0.1 hr), 1 hr (± 0.1 hr), 2 hr (± 
0.2 hr), 3 hr (± 0.2 hr), 4 hr (± 0.5 hr), 6 hr (± 0.5 hr), 8 hr (± 0.5 hr), 12 hr (± 2 hr), 24 
hr (± 2 hr) (QOD and QD arms), and 48 hr (± 2 hr) (QOD only). 
The 48-hour postdose sample (QOD arm) and the 24-hour postdose sample (QD arm) 
must be collected prior to TAS-120 administration on that day. 
During Phase 1 Dose Escalation, urine samples for pharmacodynamic analysis of TAS-120 
will be collected on C1D1 and on the C1LW (QOD arm) or on C1D1 and C1D21 (QD arm) 
at the following time points:  
pre-dose, 0 to 12 hr (±2 hr), 12 to 24 hr (±2 hr), and 24 to 48 hr (±2 hr) (QOD arm only).  
The 24 to 48 hours postdose sample (QOD arm) must be collected prior to TAS-120 
administration on Day 3 and the last Friday of Cycle 1. The 12 to 24 hours postdose 
sample (QD arm) must be collected prior to TAS-120 administration on Day 2 and Day 22 
of Cycle 1. 
 
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
03.007A.01     
Page 54 of 64 
 
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 55 of 64 
13. 
PHARMACOGENOMICS 
Cancer patients with or without FGF/FGFR abnormalities is enrolled into the first 4 
cohorts of the QOD arm and QD arm during Phase 1 Dose Escalation. The 
pharmacogenomic FGF/FGFR analysis need to be done to obtain FGF/FGFR abnormality 
confirmation.   
 
The FGF/FGFR gene abnormalities include genetic amplifications, mutations, and 
translocations. For Phase 1 Dose Escalation, patients is enrolled before central 
pharmacogenomics (PGx) laboratory confirmation of FGF/FGFR abnormality has been 
obtained.  
 
The number and percentage of patients with and without FGF/FGFR abnormality will be 
summarized by dose level and overall.  
All collected information for pharmacogenomic analyses from local and central 
laboratories will be listed. Other summaries and statistical analyses may be performed 
as appropriate. 
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 56 of 64 
14. 
INTERIM ANALYSES 
No formal interim analysis is planned with respect to stopping the trial early or for lack 
of efficacy purpose.  
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 57 of 64 
15. 
CHANGE FROM ANALYSIS PLANNED IN PROTOCOL 
There are no changes from the analysis planned in the protocol. 
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Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 58 of 64 
16. 
REFERENCE LIST 
1. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in 
solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009 
Jan;45(2):228-47. 
2. Durie BGM, Harousseau JL, Miguel JS, et al. International uniform response 
criteria for multiple myeloma. Leukemia. 2006 Sep; 20(9):1467-73. 
 
 
 
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 59 of 64 
17. 
PROGRAMMING CONSIDERATIONS 
The following conventions are some recommended approaches for the study. 
All tables, data listings, figures (TLFs), and statistical analyses will be generated using 
SAS® 9.3 or later (SAS® Institute Inc., Cary, NC, USA). The computer-generated table, 
listing and figure output will adhere to the following specifications.   
17.1. GENERAL CONSIDERATIONS 
• 
A separate SAS program will be created for each output. 
• 
Each output will be stored in a separate file. 
• 
Output files will be delivered in Word format. 
17.2. TABLE, LISTING, AND FIGURE FORMAT 
17.2.1. 
General 
• 
All TLFs will be produced in landscape format, unless otherwise specified. 
• 
All TLFs will be produced using the Courier New font, size 8  
• 
The data displays for all TLFs will have a 1.5-inch binding margin on top of a 
landscape oriented page and a minimum 1-inch margin on the other 3 sides. 
• 
Headers and footers for figures will be in Courier New font, size 8. 
• 
Legends will be used for all figures with more than 1 variable, group, or item 
displayed. 
• 
TLFs will be in black and white (no color), unless otherwise specified 
• 
Specialized text styles, such as bolding, italics, borders, shading, and superscripted 
and subscripted text, will not be used in the TLFs, unless otherwise specified. On 
some occasions, superscripts 1, 2, or 3 may be used (see below). 
• 
Only standard keyboard characters will be used in the TLFs. Special characters, such 
as non-printable control characters, printer-specific, or font-specific characters, will 
not be used. Hexadecimal-derived characters will be used, where possible, if they 
are appropriate to help display math symbols (e.g., μ). Certain subscripts and 
superscripts (e.g., cm2, Cmax) will be employed on a case-by-case basis. 
• 
Mixed case will be used for all titles, footnotes, column headers, and programmer-
supplied formats, as appropriate. 
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 60 of 64 
17.2.2. 
Headers 
• 
All output should have the following header at the top left of each page: 
<Sponsor Name> Protocol XXX (INC Research study number xxx)      
          
Draft/Final Run <date> 
• 
All output should have Page n of N at the top or bottom right corner of each page. 
TLFs should be internally paginated in relation to the total length (i.e., the page 
number should appear sequentially as page n of N, where N is the total number of 
pages in the table). 
• 
The date (date output was generated) should appear along with program name and 
location as the last footer on each page. 
17.2.3. 
Display Titles 
• 
Each TLF should be identified by the designation and a numeral. (i.e., Table 14.1.1). 
ICH E3 numbering is will be used. A decimal system (x.y and x.y.z) should be used to 
identify TLFs with related contents. The title is centered. The analysis set should be 
identified on the line immediately following the title. The title and table 
designation are single spaced. A solid line spanning the margins will separate the 
display titles from the column headers. There will be 1 blank line between the last 
title and the solid line. 
 
Table x.y.z 
First Line of Title 
Second Line of Title if Needed 
As Treated Population 
17.2.4. 
Column Headers 
• 
Column headings should be displayed immediately below the solid line described 
above in initial upper-case characters.  
• 
For numeric variables, include “unit” in column or row heading when appropriate. 
• 
Analysis set sizes will be presented for each cohort in the column heading as (N=xx) 
(or in the row headings if applicable). This is distinct from the ‘n’ used for the 
descriptive statistics representing the number of patients in the analysis set. 
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 61 of 64 
17.2.5. 
Body of the Data Display 
17.2.5.1. General Conventions 
Data in columns of a table or listing should be formatted as follows: 
• 
alphanumeric values are left-justified; 
• 
whole numbers (e.g., counts) are right-justified; and 
• 
numbers containing fractional portions are decimal aligned. 
 
17.2.5.2. Table Conventions 
• 
Units will be included where available 
• 
If the categories of a parameter are ordered, then all categories between the 
maximum and minimum category should be presented in the table, even if n=0 for 
all dose levels in a given category that is between the minimum and maximum level 
for that parameter. For example, the frequency distribution for symptom severity 
would appear as: 
Severity 
Rating 
N 
severe 
0 
moderate 
8 
mild 
3 
Where percentages are presented in these tables, zero percentages will not be 
presented and so any counts of 0 will be presented as 0 and not as 0 (0%). 
• 
If the categories are not ordered (e.g., Medical History, Reasons for Discontinuation 
from the Study, etc.), then only those categories for which there is at least 1 
subject represented in 1 or more dose levels should be included. 
• 
An Unknown or Missing category may be added to any parameter for which 
information is not available for 1 or more patients.  
• 
Unless otherwise specified, the estimated mean and median for a set of values 
should be printed out to 1 more significant digit than the original values, and 
standard deviations should be printed out to 2 more significant digits than the 
original values. The minimum and maximum should report the same significant digits 
as the original values. For example, for systolic blood pressure: 
N 
  XX 
Mean 
XXX.X 
Std Dev 
     X.XX 
Median 
XXX.X 
Minimum 
XXX 
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 62 of 64 
Maximum 
XXX 
• 
Percentage values should be printed to one decimal place, in parentheses with no 
spaces, one space after the count (e.g., 7 (12.8%), 13 (5.4%)). Pre-determine how to 
display values that round down to 0.0.  A common convention is to display as '<0.1', 
or as appropriate with additional decimal places. Unless otherwise noted, for all 
percentages, the number of patients in the analysis set for the treatment group who 
have an observation will be the denominator. Percentages after zero counts should 
not be displayed and percentages equating to 100% should be presented as 100%, 
without any decimal places.  
• 
Tabular display of data for medical history, and all tabular displays of adverse event 
data should be presented by SOC with the highest occurrence in the overall in 
decreasing order, assuming all terms are coded. Within SOC, medical history and 
adverse events (by preferred term) should be displayed in decreasing order. If 
incidence for more than 1 term is identical, they should then be sorted 
alphabetically. Missing descriptive statistics which cannot be estimated should be 
reported as “-”. 
• 
The percentage of patients is normally calculated as a proportion of the number of 
patients assessed in the relevant dose level (or overall) for the analysis set 
presented. However, careful consideration is required in many instances due to the 
complicated nature of selecting the denominator, usually the appropriate number of 
patients exposed. Describe details of this in footnotes or programming notes. 
• 
For categorical summaries (number and percentage of patients) where a subject can 
be included in more than one category, describe in a footnote or programming note 
if the subject should be included in the summary statistics for all relevant categories 
or just 1 category and the criteria for selecting the criteria. 
• 
Where a category with a subheading (such as system organ class) has to be split over 
more than one page, output the subheading followed by “(cont)” at the top of each 
subsequent page.  The overall summary statistics for the subheading should only be 
output on the first relevant page. 
 
17.2.5.3. Listing Conventions 
• 
Listings will be sorted for presentation in order of dose level, patient number, 
visit/collection day, and visit/collection time. 
• 
Dates should be printed in SAS® DATE9.format (“ddMMMyyyy”: 01JUL2000). Missing 
portions of dates should be represented on subject listings as dashes (--JUL2000).  
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 63 of 64 
• 
All observed time values must be presented using a 24-hour clock HH:MM or 
HH:MM:SS format (e.g., 11:26:45, or 11:26). Time will only be reported if it was 
measured as part of the study. 
• 
Units will be included where available 
 
17.2.5.4. Figure Conventions 
• 
Unless otherwise specified, for all figures, study visits and time points will be 
displayed on the X-axis and endpoint (e.g., treatment mean change from Baseline) 
values will be displayed on the Y-axis. 
17.2.6. 
Footnotes 
• 
A solid line spanning the margins will separate the body of the data display from the 
footnotes.  
• 
All footnotes will be left justified with single-line spacing immediately below the 
solid line underneath the data display. 
• 
Footnotes should always begin with “Note:” if an informational footnote, or 1, 2, 3, 
etc. if a reference footnote. Each new footnote should start on a new line where 
possible. 
• 
Footnotes will be present on the page where they are first referenced and 
thereafter on each page of the table, unless the footnote is specific only to certain 
pages. Subject specific footnotes should be avoided. 
• 
Footnotes will be used sparingly and must add value to the table, figure, or data 
listing. If more than six lines of footnotes are planned, then a cover page may be 
used to display footnotes, and only those essential to comprehension of the data will 
be repeated on each page.  
• 
The last line of the footnote section will be a standard source line that indicates the 
name of the program used to produce the data display, date the program was run, 
and the listing source (i.e., ‘Program : myxxxxxx.sas    Listing source: 16.x.y.z’). 
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INC Project Number: 
 
 
Sponsor: Taiho Oncology, Inc. 
Protocol: TPU-TAS-120-101 
Version: 3.3, Phase 1 Dose Escalation Only 
Statistical Analysis Plan 
 
03.007A.01     
Page 64 of 64 
18. 
QUALITY CONTROL 
SAS programs are developed to produce clinical trial output such as analysis data sets, 
summary tables, data listings, figures or statistical analyses. INC Research SOP 
 provide an overview of the development of such SAS programs. 
INC Research SOP 
describes the quality control procedures that are 
performed for all SAS programs and output. Quality control is defined here as the 
operational techniques and activities undertaken to verify that the SAS programs 
produce the proper clinical trial output by checking for their logic, efficiency and 
commenting and by review of the produced output.” 
For all data sets, tables and listings generated by SAS, INC Biostatistics will create SAS 
codes independently, and then use SAS PROC COMPARE procedure to perform 100% 
electronic comparison for all numerical and character values. In addition, the Lead 
Biostatistician, Lead Programmer and Senior Statistical Reviewer will review all TLFs for 
consistency and accuracy. 
 
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Taiho Oncology, Inc. 
 
 
Statistical Analysis Plan (Phase I Expansion)– Protocol: TPU-TAS-120-101 
   25 OCT 2019 
 
1 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
VERSION: 2.0 
DATE OF PLAN: 25 OCT 2019 
 
PROTOCOL NUMBER: 
TPU-TAS-120-101 
STUDY TITLE: 
PHASE ½ STUDY IN PATIENTS WITH ADVANCED SOLID TUMORS 
HARBORING FGF/FGFR ABERRATIONS (PHASE I EXPANSION) 
 
SPONSOR: 
Taiho Oncology, Inc. 
101 Carnegie Center 
Princeton, NJ USA 08540 
+1 (609) 750-5300 
 
This trial was conducted in accordance with the ethical principles of Good Clinical Practice (GCP), according to 
the International Conference on Harmonization (ICH) Harmonized Tripartite Guideline. 
 
Confidentiality Statement 
The information in this document contains trade secrets and commercial information that are privileged or 
confidential and may not be disclosed unless such disclosure is required by applicable law or regulations. 
In any event, persons to whom the information is disclosed must be informed that the information is privileged 
or confidential and may not be further disclosed by them.  These restrictions on disclosure will apply equally to 
all future information supplied to you that is indicated as privileged or confidential. 


Taiho Oncology, Inc. 
 
 
Statistical Analysis Plan (Phase I Expansion)– Protocol: TPU-TAS-120-101 
   25 OCT 2019 
 
 
2 
 
 
  
 
STATISTICAL ANALYSIS PLAN 
 
APPROVAL PAGE 
 
PHASE ½ STUDY IN PATIENTS WITH ADVANCED SOLID TUMORS 
HARBORING FGF/FGFR ABERRATIONS (PHASE I EXPANSION) 
 
Protocol TPU-TAS-120-101 
Version 2.0 
 
 
Prepared by: 
 
 
 
 
 
 
Signature 
 
Date 
 
 
Approved by:  
 
 
 
 
 
 
Signature 
 
Date 
 
 
 
 
 
Signature 
 
Date 
 
 
 
 
 
PPD
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Taiho Oncology, Inc. 
 
 
Statistical Analysis Plan (Phase I Expansion)– Protocol: TPU-TAS-120-101 
   25 OCT 2019 
 
 
3 
 
 
  
 
TABLE OF CONTENTS 
TABLE OF CONTENTS .................................................................................................................2 
LIST OF TABLES ...........................................................................................................................5 
1. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS...............................6 
2. 
INTRODUCTION ........................................................................................................8 
3. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................10 
3.1. 
Study Objectives .........................................................................................................10 
3.1.1. 
Primary Objectives .....................................................................................................10 
3.1.2. 
Secondary Objectives .................................................................................................10 
3.2. 
Study Endpoints ..........................................................................................................10 
3.2.1. 
Primary Endpoints ......................................................................................................10 
3.2.2. 
Secondary Endpoints ..................................................................................................10 
4. 
STUDY DESCRIPTION ............................................................................................12 
4.1. 
Summary of Study Design ..........................................................................................12 
4.2. 
Treatment Assignment and Blinding/Unblinding .......................................................17 
4.3. 
Determination of Sample Size ....................................................................................17 
5. 
STUDY PERIODS, TREATMENT REGIMENS, AND POPULATIONS 
FOR ANALYSIS ........................................................................................................20 
5.1. 
Study Periods ..............................................................................................................20 
5.2. 
Treatment Groups .......................................................................................................20 
5.3. 
Populations for Analysis .............................................................................................20 
5.4. 
Timing of Analysis .....................................................................................................20 
6. 
STATISTICAL ANALYSIS ......................................................................................21 
6.1. 
General Methods .........................................................................................................21 
6.2. 
Study Conduct ............................................................................................................22 
6.2.1. 
Accrual ........................................................................................................................22 
6.2.2. 
Protocol Deviations ....................................................................................................22 
6.3. 
Study Population .........................................................................................................22 
6.3.1. 
Patient Disposition ......................................................................................................22 
6.3.2. 
Demographic and Other Baseline Characteristics ......................................................22 
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Taiho Oncology, Inc. 
 
 
Statistical Analysis Plan (Phase I Expansion)– Protocol: TPU-TAS-120-101 
   25 OCT 2019 
 
 
4 
 
 
  
 
6.3.3. 
Medical History ..........................................................................................................23 
6.3.4. 
Prior/Concomitant Therapies ......................................................................................23 
6.4. 
Efficacy Analyses .......................................................................................................24 
6.4.1. 
Primary Efficacy Analyses .........................................................................................24 
6.4.2. 
Secondary Efficacy Analyses .....................................................................................25 
6.4.3. 
Other Efficacy Analyses .............................................................................................26 
6.5. 
Safety Analyses ..........................................................................................................27 
6.5.1. 
Extent of Exposure .....................................................................................................27 
6.5.2. 
Adverse Events ...........................................................................................................28 
6.5.3. 
Clinical Laboratory Evaluations .................................................................................31 
6.5.4. 
Vital Signs ..................................................................................................................33 
6.5.5. 
Electrocardiograms .....................................................................................................33 
6.5.6. 
Physical Examination .................................................................................................34 
6.5.7. 
ECOG Performance Status .........................................................................................34 
6.5.8. 
Pregnancy Test ............................................................................................................34 
6.6. 
Other Analyses ............................................................................................................34 
6.8. 
Pharmacokinetic Analyses ..........................................................................................35 
6.8.1. 
Optional Pharmacokinetic Samples ............................................................................35 
6.8.2. 
Pharmacokinetic Blood Samples ................................................................................35 
7. 
CHANGES IN PLANNED ANALYSIS ....................................................................36 
8. 
DEFINITIONS AND CONVENTIONS FOR DATA HANDLING .........................37 
8.1. 
Baseline Period ...........................................................................................................37 
8.2. 
Post-Baseline Period ...................................................................................................37 
8.3. 
AESI Definition and Conventions ..............................................................................37 
8.4. 
Time-to-Onset Definition ...........................................................................................37 
8.5. 
Time-to-Resolution Definition ...................................................................................38 
8.6. 
Multiple Adverse Events ............................................................................................39 
8.7. 
Other Data Handling Rules .........................................................................................39 
9. 
REFERENCES ...........................................................................................................41 
 
 
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Taiho Oncology, Inc. 
 
 
Statistical Analysis Plan (Phase I Expansion)– Protocol: TPU-TAS-120-101 
   25 OCT 2019 
 
 
5 
 
 
  
 
LIST OF TABLES 
Table 1. 
Study Schedule for Phase 1 Expansion 
Table 2. 
Multinomial Two-stage Design Boundaries for Group 5 (Based on Objective 
Response and Early Progression) 
Table 3. 
Summary of Group 7 Design 
Table 4. 
Definition of Study Periods 
Table 5.  
Confirmation Rules for Overall Response of PR and CR 
Table 6.    
Censoring Rules for Progression-Free Survival   
Table 7. 
Censoring Rules for Overall Survival (OS) Endpoint. 
Table 8. 
Summary of RANO Response Criteria 
Table 9.  
Laboratory Tests 
Table 10. 
Grade Categories of Eastern Cooperative Oncology Group Score 
Table 11. 
Derivation of Clustered AESI 
Table 12.  
Partial Date Imputation Rule for AE or Medication  
 
 
 
 
 
 


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1. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation  
Term 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
ATP 
Adenosine triphosphate 
BUN 
Blood urea nitrogen 
CCA 
Cholangiocarcinoma 
Ccr 
Calculated creatinine clearance  
CI 
Confidence interval 
CK 
Creatine kinase 
CK-MB 
Creatine kinase (isoform heart muscle) 
CR 
Complete response 
CSF 
Cerebrospinal fluid 
CTCAE 
Common Terminology Criteria for Adverse Events 
ctDNA 
Circulating tumor DNA 
CYP 
Cytochrome P450 
DCR 
Disease control rate 
DOR 
Duration of response 
eCCA 
Extra-hepatic cholangiocarcinoma 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EOT 
End-of-treatment 
EP 
Early progression 
EPR 
Early progression rate 
FFPE  
Formalin fixed paraffin embedded 
FGF 
Fibroblast growth factor 
FGFR 
Fibroblast growth factor receptor 
GBM 
Glioblastoma multiforme  
GCP 
Good Clinical Practice 
Gd-MRI   
Gadolinium-based magnetic resonance imaging 
iCCA 
Intra-hepatic cholangiocarcinoma 
ICH 
International Council for Harmonisation 
INR 
International normalized ratio 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
Magnetic resonance imaging 
 
 
 
 
 
 
 
 


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Abbreviation  
Term 
ms 
Milliseconds 
MTD 
Maximum tolerated dose 
NCI 
National Cancer Institute 
NSCLC 
Non-small cell lung cancer 
PFS 
Progression-free survival 
PK 
Pharmacokinetic(s) 
PR 
Partial response 
PROs 
Patient-Reported Outcomes 
PT 
Preferred term 
QD 
Once daily (continuous) dosing 
QTcF 
Fridericia’s corrected QT interval  
R 
Response 
RANO 
Response Assessment in Neuro-Oncology 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RP2D 
Recommended Phase 2 dose 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Stable disease 
SOC 
System Organ Class 
WHO 
World Health Organization 
WOCBP 
Women of child-bearing potential 


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2. 
INTRODUCTION 
The purpose of this statistical analysis plan (SAP) is to describe the planned analyses and data 
displays to be included in the Clinical Study Report (CSR) for Protocol TAS-120-101. 
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. 
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 fusions have been identified as an early driver of oncogenic events.  
These gene 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 
survival (OS) of 10% and 0%, respectively. For such patients, chemotherapy and supportive care 


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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. 
The Phase I Expansion part of the study included a total of 8 disease 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.  
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. 
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. 


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3. 
STUDY OBJECTIVES AND ENDPOINTS 
3.1. 
Study Objectives 
3.1.1. 
Primary Objectives 
• 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 
• 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 
3.1.2. 
Secondary Objectives 
• To investigate the safety of TAS-120 
• To evaluate Disease Control Rate (DCR), Duration of Response (DOR) and PFS 
3.2. 
Study Endpoints 
3.2.1. 
Primary Endpoints 
• Objective response rate (ORR, according to RECIST 1.1 and EPR for primary CNS 
tumors). Objective response rate is defined as the proportion of patients who had best 
overall response (BOR) of CR or PR. 
3.2.2. 
Secondary Endpoints 
• Duration of response (DOR)  
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Duration of response is defined as the time from the first documented response (CR or 
PR) to the first documented objective progressive disease (PD) or death due to any cause.   
• Disease control rate (DCR)  
Disease control rate is 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.  
• Progression-free survival (PFS)  
PFS is defined as the time from the first dosing date to the date of the first documented 
progression or death due to any cause, whichever occurs first.  
• Overall survival (OS)  
OS is defined as the time between the first dosing date and the date of death.  
• Safety and Tolerability of TAS-120 
Safety will be analyzed through the incidence of death, adverse event, concomitant 
medications, physical examination, vital sign measurements, clinical laboratory results, 
ECG results, ECOG performance status, and other safety observations at the time points 
indicated in the Study Schedule of Assessments (Table 1) will be monitored and recorded. 
The data will be summarized. 
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4. 
STUDY DESCRIPTION 
4.1. 
Summary of Study Design 
This is an open-label, nonrandomized, and Phase I Expansion study of TAS-120, evaluating the 
efficacy, safety, and antitumor activity of the RP2D 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.  
As of Amendment 6, the Phase 1 Dose Escalation Phase is completed and MTD/RP2D of 20 mg 
QD was established.  
TAS-120 will be administered orally at 20 mg, QD in 21-day cycles. Approximately 185 patients 
will be enrolled.  Patients will be assigned to one of 8 disease groups based on  
diagnosis, prior therapy, and FGFR aberration: 
• Group 1 (Enrollment suspended as of Amendment 7): Patients with intrahepatic 
or extrahepatic CCA harboring FGFR2 gene fusions or rearrangements. 
• Group 2: Patients with intrahepatic or extrahepatic CCA harboring FGFR2 gene 
fusions or rearrangements that have not received or received less than 1 cycle of 
prior chemotherapy (due to intolerance or patient refusal) 
• Group 3 (Enrollment suspended as of Amendment 7): CCA (iCCA or eCCA) with 
FGFR2 gene fusions or rearrangements treated with prior FGFR inhibitors 
• Group 4 (Enrollment suspended as of Amendment 7): CCA (iCCA or eCCA) with 
other FGFR abnormalities, i.e., gene mutations, rearrangements or amplifications 
• Group 5: Patients with primary CNS tumors harboring FGFR gene fusions or 
FGFR1 activating mutations 
• Group 6 (Enrollment suspended as of Amendment 7): Patients with advanced 
urothelial carcinoma harboring FGFR3 gene fusions or FGFR3 activating 
mutations  
• Group 7: Patients with any tumor type not included in one of the prior groups, 
harboring FGFR2 amplification (no minimum number of copies).  
• Group 8 (Enrollment suspended as of Amendment 7): Patients with any tumor 
type not included in one of the prior groups, harboring FGFR gene fusions or 
activating mutations 
 
 
 


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Table 1. 
Study Schedule for Phase 1 Expansion 
NOTE: Evaluations on D1 of a cycle should be performed within 24 hours prior to dosing, unless otherwise noted.  Procedures already 
performed during the screening period within 72 hours prior to dosing do not need to be repeated on C1D1. 
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). 
 
Screening 
Period 
(Within 
28 Days 
Prior to 
First 
Dose) 
Treatment Period (1 cycle = 21 days) 
Safety  
Follow-up 
Survival Follow-up 
Period 
Notes 
Cycle 1 
Cycles 
≥2 
End of Tx (+0-
7 days) 
30 (±3) days 
After Last 
Dose
  
Day 
Day 
1  
4  
(±1d
) 
8 
(±3d
) 
15 
(±3d
) 
1 (±3d) 
Written informed consent 
X 
 
 
 
 
 
 
 
 
 
Review eligibility criteria 
X 
X 
 
 
 
 
 
 
 
 
Demographics/medical history 
X 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
 
 
 
X 
X 
X 
 
   
Review of pre-existing signs and 
symptoms 
X 
X 
 
 
 
 
 
 
 
 
Tumor tissue sample collection 
(X) 
 
At any time during the study; tumor tissue 
collection is mandatory if tissue is available. 
Vital signs 
X 
X 
 
 
 
X 
X 
X 
 
Heart rate, blood pressure, body temperature, and 
respiration rate. 
Height and Weight 
X 
X 
 
 
 
X 
X 
X 
 
Height at screening only. 
Ophthalmological examination 
X 
 
 
 
 
(X) 
X 
X 
 
At screening and 4-6 weeks after first dose; 
additional on-study evaluation as needed due to 
local requirements, physician judgment, and/or 
symptoms or signs of mineral deposits. 
Neurological examination 
 
X 
(X) 
 
 
 
(X) 
X 
X 
 
As clinically indicated after screening, using same 
methods used at screening. 
Neurological examination as part 
of RANO 
(Group 5) 
X 
(X) 
 
 
 
(X) 
X 
X 
 
For patients with primary CNS tumors, a 
neurological examination must be performed within 
1 week of the date of the Gd-MRI performed at 
screening and as part of RANO response 
assessment. 
ECOG performance status 
X 
X 
 
 
 
X 
X 
X 
 
 


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Screening 
Period 
(Within 
28 Days 
Prior to 
First 
Dose) 
Treatment Period (1 cycle = 21 days) 
Safety  
Follow-up 
Survival Follow-up 
Period 
Notes 
Cycle 1 
Cycles 
≥2 
End of Tx (+0-
7 days) 
30 (±3) days 
After Last 
Dose
  
Day 
Day 
1  
4  
(±1d
) 
8 
(±3d
) 
15 
(±3d
) 
1 (±3d) 
12-Lead Electrocardiogram 
X 
X 
 
 
 
X 
X 
X 
 
At screening and 2 hours (±15 minutes) after dosing 
on D1 of each cycle. 
Hematology and coagulation 
X 
X 
 
X 
X 
X 
X 
X 
 
Within 24 hours prior to treatment on D1 of each 
cycle, any time on C1D8 and C1D15, and as 
clinically indicated. 
Chemistry (Serum or plasma) 
X 
X 
(X) 
X 
X 
X 
X 
X 
 
Within 24 hours prior to treatment on D1 of each 
cycle, any time on C1D8 and C1D15, and as 
clinically indicated.  Additional collection for 
phosphorus only at C1D4.   
Urinalysis (Urine dipstick) 
X 
X 
 
 
 
X 
X 
X 
 
 
Pregnancy test 
X 
X 
 
 
 
X 
X 
X 
 
Serum pregnancy test required for WOCBP at 
screening and end of treatment; serum or urine 
pregnancy test required at all other timepoints. 
Blood PK Sampling (Required) 
 
 
 
 
 
X 
 
 
 
Blood samples (1 mL) collected C2D1 pre-dose and 
at 1h and 3h (±30 min) post-dose.  Additional 
samples collected pre-dose on C3D1 and C4D1. 
Blood PK Sampling (Optional) 
 
Blood samples (minimum 1 mL) collected 
any day if needed, prior to dose and 1, 2, 3, 
4, 6, and 24 hours post-dose.   
 
 
 
See also protocol Section 10.13.1. 
Blood and CSF PK Sampling 
(Blood, CSF; Optional) 
(Group 5 only) 
 
 
(X) 
 
 
 
Blood and CSF samples (minimum 1 mL of whole 
blood and CSF each) collected 2-4 hours after dose 
on C2D1.  See also protocol Section 10.1.1. 
ctDNA blood samples 
X 
 
 
 
 
 
(X) 
 
 
Minimum of 20 mL whole blood at screening 
(mandatory) and EOT (optional). 


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Screening 
Period 
(Within 
28 Days 
Prior to 
First 
Dose) 
Treatment Period (1 cycle = 21 days) 
Safety  
Follow-up 
Survival Follow-up 
Period 
Notes 
Cycle 1 
Cycles 
≥2 
End of Tx (+0-
7 days) 
30 (±3) days 
After Last 
Dose
  
Day 
Day 
1  
4  
(±1d
) 
8 
(±3d
) 
15 
(±3d
) 
1 (±3d) 
Prior & concomitant medications, 
AE assessments 
X  
 
X 
X 
 
Collect from the time informed consent (ICF) is signed 
through 30 days after administration of the last dose of 
TAS-120. 
Tumor assessments / scans 
X 
 
 
 
 
X 
X 
 
(X) 
Perform the same tumor assessments/scans obtained at 
screening at the end of every 2 cycles (up to +2 weeks) up 
to Cycle 4. Thereafter tumor assessments may be 
performed every 3 cycles (± 7 days), or as clinically 
indicated, until radiologic disease progression or initiation 
of new anticancer therapy (whichever occurs first).  
At EOT, tumor assessment must be performed if the prior 
scan was performed ≥9 weeks prior to discontinuation of 
treatment if the patient discontinued for reasons other than 
radiologic disease progression. See also protocol Section 
10.17. 
After EOT, patients who discontinued for reasons other 
than radiologic disease progression should continue to 
receive tumor assessments every 3 cycles (± 7 days), or as 
clinically indicated, until radiologic disease progression or 
initiation of new anticancer therapy (whichever occurs 
first).  
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Screening 
Period 
(Within 
28 Days 
Prior to 
First 
Dose) 
Treatment Period (1 cycle = 21 days) 
Safety  
Follow-up 
Survival Follow-up 
Period 
Notes 
Cycle 1 
Cycles 
≥2 
End of Tx (+0-
7 days) 
30 (±3) days 
After Last 
Dose
  
Day 
Day 
1  
4  
(±1d
) 
8 
(±3d
) 
15 
(±3d
) 
1 (±3d) 
Survival status 
 
 
 
 
 
 
 
 
X 
After discontinuation of treatment, survival follow-up in a 
given group should occur every 3 months (±2 weeks) for 
up to 12 months after last patient enrolled in that group. 
TAS-120 Dosing 
 
 
 
 
 
 
 
 
 
Patients are required to fast for at least 2 hours before and 
1 hour after each administration of TAS-120; patients are 
permitted to drink water during this period.  TAS-120 
should be administered in the morning or evening, at the 
same time (if possible) each day.  See protocol Section 
9.1.1 
 
 
 
 
 
 
 
 
 
 
 


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4.2. 
Treatment Assignment and Blinding/Unblinding 
After the patient’s initial eligibility is established and informed consent has been obtained, the 20 
mg QD of TAS-120 will be administered orally in patients with tumors harboring specific 
FGF/FGFR aberration. The treatment of TAS-120 will be continued with 21-day treatment cycle 
until at least one of the criteria for study discontinuation criteria is met.  
 
This is an open label study. The blinding/unblinding is not applicable in this study. 
Primary endpoints for CCA and CNS patients, ORR will be based on the independent review of 
images by the Core Imaging Laboratory according to the RECIST 1.1. For the other tumor types, 
ORR will be based on investigators assessment.  
4.3. 
Determination of Sample Size 
For this Phase I Expansion study, up to approximately 185 patients will be enrolled among the 
different tumor types as outlined below: 
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5. 
STUDY PERIODS, TREATMENT REGIMENS, AND 
POPULATIONS FOR ANALYSIS 
5.1. 
Study Periods 
The study periods are defined in the table 4 below. 
Table 4. 
Definition of Study Periods for Analysis 
Period 
Definition 
Baseline / Screening 
From the day of ICF signature (up to 28 days before first dose) to the day and time 
of the first dose of study drug. 
On-treatment  
From the date of first dose of study therapy through 30 days after the last dose of 
study therapy.  Unless otherwise specified, the on-treatment period will be the 
basis for the summaries of safety. 
Abbreviations: ICF=informed consent form. 
 
5.2. 
Treatment Groups 
 
There are 8 disease groups in this Phase I Expansion study as described in section 4.1 of this 
SAP. 20 mg QD of TAS-120 has been selected as the dose for each of the 8 disease groups.  
 
In addition, in early portion of the Phase I Expansion study, a small number of patients were 
treated with 16 mg DQ and then followed by 20 mg QD.  
5.3. 
Populations for Analysis 
• 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.  
• Pharmacokinetics and Pharmacodynamics 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.  
• Efficacy Population:  all treated Patients (Safety Population). 
5.4. 
Timing of Analysis 
The final analysis will be performed when at least 90% of all treated patients had 4 months of 
follow-up.  
The timing of the interim analysis please referred to Section 4.3 Determination of Sample Size of 
this SAP.  


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6. 
STATISTICAL ANALYSIS 
6.1. 
General Methods 
All relevant data will be presented in patient level data listings. 
All categorical (binary and ordinal) data will be summarized by tumor type groups using 
frequency counts and percentages of patients. Percentage will be calculated based on groups in 
the study population as the denominator. The continuous variables will be summarized using 
number of non-missing observation (n), mean, standard deviation (SD), median, minimum and 
maximum unless otherwise specified. The number of events and censorings will be reported for 
time-to-event analysis. All estimations will include a point estimate and the corresponding 95% 
confidence interval. 
Summary tables will be presented by the disease type. Data listings will be presented with the 
groups and patient ID. The tables by sub-groups such as: age groups, gender, races, ECOG 
categories, and will be also summarized.  
Analysis Cohort based on disease type (disease group 1 through group 8) are assigned as follows. 
Unless otherwise specified, by-cohort analysis will be included in tables and figures. 
• Cohort 1: Patients with Cholangiocarcinoma (CCA). It combines disease group 1 to 4 
• Cohort 2: Patients with primary CNS tumor. It’s the patients from disease group 5 
• Cohort 3: Patients with advanced urothelial carcinoma. It’s the patients from disease 
group 6 
• Cohort 4: Patients with breast cancer or gastric cancer. It’s the patients from disease 
group 7 
• Cohort 5: Patients with the tumor types in disease group 8, harboring FGFR gene fusions 
or activating mutations 
• Cohort 6: Patients not included in cohort 1 to cohort 5 
For concomitant medications and adverse events, the cycles are determined based on their 
start/onset dates. For other collected data, the cycles are determined based on their visit dates.  
When there are multiple laboratory records for a scheduled visit, the one closest to the target date 
(relative to the Day 1 in that cycle) will be used for analysis. If there are two or more records with 
the same time period to the target date, the later one will be used for analysis.  
Time to event distribution (e.g. progression free survival, overall survival, time to response, and 
duration of response) will be estimated using Kaplan Meier techniques. When appropriate, the 
median along with the corresponding log-log transformed 95% CI will be estimated. Rates at 
fixed time points will be derived from the Kaplan Meier estimate and corresponding confidence 
interval will be derived based on Greenwood formula for variance derivation and on log-log 
transformation applied on the survivor function S(t). Confidence intervals for binomial 
proportions, ORR and DCR, will be derived using the Clopper-Pearson method. 
 


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For patients who were also treated with 16 mg QD during early portion of the Phase I Expansion 
of the study, separate analysis will be presented.  
 
All the analyses of efficacy, safety, and PK data for this study will be performed using SAS® 
statistical software package, Version 9.3 or a later version.  
6.2. 
Study Conduct 
6.2.1. 
Accrual 
The accrual will be summarized on the enrolled population separately for each cohort. The number 
of patients accrued by region and investigational site will be summarized for all enrolled patients. 
A patient level listing of accrual will also be produced. 
6.2.2. 
Protocol Deviations 
Important protocol deviation is defined as a subset of protocol deviations that may significantly 
impact the completeness, accuracy, and/or reliability of the study data or that may significantly 
affect the patient’s rights, safety or well-being.    
Important protocol deviations will be included in the Clinical Study Report (CSR). These 
include:   Important ICF issues, inclusion/exclusion criteria not met, withdrawal criteria not 
followed; wrong treatment, incorrect dose/ overdose based on protocol definitions, important 
deviations based on protocol design, and other important GCP deviations.  All protocol 
deviations will be tracked and corrective actions implemented. 
6.3. 
Study Population 
6.3.1. 
Patient Disposition 
The number of patients in all treated population will be summarized by analysis Cohorts along 
with the reason for exclusion from the population.  In addition, patients’ status with regard to 
study treatment and follow-up will also be summarized, along with the reasons for study 
discontinuations. 
 
In addition, summary tables will also be provided for the iCCA patients: with FGFR2 
rearrangement, without FGFR2 rearrangement, with FGFR2 rearrangement with GEM/CIS and 
without FGFRi Prior Treatment, with FGFR2 rearrangement with FGFRi prior treatment. 
6.3.2. 
Demographic and Other Baseline Characteristics 
The following baseline characteristics will be summarized by Cohort, as well as by these 4 
categories for the iCCA patients: with FGFR2 rearrangement, without FGFR2 rearrangement, 
with FGFR2 rearrangement with GEM/CIS and without FGFRi Prior Treatment, with FGFR2 
rearrangement with FGFRi prior treatment. Listings will also be provided: 
• Age (descriptive statistics) 
• Age category (<65, >=65) 


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• Gender (male, female) 
• Race groups (Caucasian/white, Black, Asian/Oriental, American Indian or Alaska Native, 
Native Hawaiian or Other Pacific Islander, Other) 
• Ethnicity (Hispanic/Latino, Not Hispanic/Latino) 
• ECOG Performance Status (1, 0) 
• Baseline Weight (kg) 
• Baseline Height (cm) 
• Prior surgical resection of primary tumor 
• Locally advanced disease only 
• Metastatic disease 
• Region of enrollment (Asia (excluding Japan), Japan, Rest-of-the-World) 
6.3.3. 
Medical History 
Medical terms in medical history will be coded according to the Medical Dictionary for Regulatory 
Activities (MedDRA 18.1).  Medical history will be listed by patient number, start date and end 
date, and CTCAE grade. The treatment start date and end date versus the first dose date maybe 
listed. 
6.3.4. 
Prior/Concomitant Therapies 
Prior or concomitant medications and therapies will be collected from the time of informed consent 
through 30 days after administration of last dose of study medication.  
Medications and therapies which started and stopped prior to the first dose of TAS-120 are 
considered as prior medications. Medications and therapies which started prior to the first dose of 
TAS-120 and continued into the treatment period are considered as prior and concomitant 
medications. Medications or therapies with a start date from first dose of TAS-120 to 30 days after 
administration of the last dose of TAS-120 will be considered as concomitant medications and 
therapies.  
Prior and concomitant medications will be coded according to World Health Organization 
(WHO) Drug Dictionary (WHODrug version March 2014) for Concomitant Medication. The 
concomitant medications will be summarized by ATC level 2 (Therapeutic Main Group) and 
ATC level 4 (Chemical/Therapeutic Subgroup) using the number and percentage of patients. 
Medications will be sorted in descending order of frequency of ATC level 2 and ATC level 4 
within ATC level 2 in the total column. A patient will be counted only once within each level of 
summation if the patient has taken a medication more than once. 
All prior and concomitant medications and therapies will be listed in patient level. 


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6.3.4.1. 
Prior Anticancer Therapy 
The baseline cancer types with number of patients with confirmed FGFR2 gene fusions or other 
FGF/FGFR aberrations, and prior FGFRi treatment will be summarized. A patient level listing 
will also be provided. 
Pre-study surgery and prior radiation therapy will be summarized by tumor type groups. For pre-
study surgery, the number and percentage of patients with biopsy, primary tumor removal, 
metastatic tumor removal, and other surgeries will be reported. For prior-radiation therapy, the 
number and percentage of patients with palliative and therapeutic radiation therapies will be 
presented in a summary table. 
All prior anticancer therapies (adjuvant therapies, neoadjuvant therapies, therapies for 
advanced/metastatic disease, and maintenance therapies) will be summarized. The number of 
patients with 1, 2, 3 and >=4 prior regimens will be summarized for all anticancer therapies and 
for advanced/metastatic disease only. The number of patients and percent with best of response 
for prior anticancer therapy will also be summarized.   
All collected information for cancer diagnosis, pre-study surgery, prior-radiation therapy, and 
prior anti-cancer therapy will be summarized and listed. 
6.3.4.2. 
Other Prior/Concomitant Therapy 
Prior/current medication will be classified by anatomic and therapeutic classes. Agents and 
medication will be reported using the generic name. A listing by patient will also be provided. 
In addition, percentage of subjects who received concomitant medication for management of 
hyperphosphatemia will be reported by cohort (percentages of treated subjects by medication 
class and generic term).  
Total duration of medications (excluding overlaps) given for management of hyperphosphatemia 
will be also summarized. 
6.4. 
Efficacy Analyses 
6.4.1. 
Primary Efficacy Analyses 
The primary endpoint, Objective Response Rate (ORR), defined as the proportion of patients 
who achieved best overall response of partial response (PR) or complete response (CR) in the 
Efficacy Population for solid tumor patients. It will be calculated from the best of overall 
response recorded from the start of treatment until progression disease or start of subsequent new 
anticancer treatment. The overall response can be derived based on target lesion response, non-
target response as well as the emergence of new lesion for patients with measurable disease at 
baseline. Rules for Overall Response derivation is summarized in Table 5.  
A minimum of 4-week interval between two tumor measurements is required to confirm PR or 
CR. A minimum of 6-week interval between initial of treatment (first dose date) and tumor 
measurement is required for SD. The confirmation rule is shown in Table 5. 
 


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The 95% confidence interval (binomial proportion confidence interval) for ORR will be 
constructed with Clopper-Pearson 95% CI. 
 
The ORR summary based on Independent Review will be presented for iCCA patients by the 4 
categories of: with FGFR2 rearrangement, without FGFR2 rearrangement, with FGFR2 
rearrangement with GEM/CIS and without FGFRi Prior Treatment, with FGFR2 rearrangement 
with FGFRi prior treatment. 
In addition, ORR will be presented based on data from the Investigator Review.  
        Table 5. Confirmation Rule for Overall Response of PR and CR 
Earlier Response 
(to be confirmed) 
Later Response 
(confirmation) 
Confirmed Response 
CR 
CR 
CR 
CR 
Not CR or missing 
SD 
PR 
CR or PR 
PR 
PR 
SD or PD or missing 
SD 
PR 
SD and then PR (only one SD in between) 
PR 
SD 
n/a – no confirmation needed 
SD 
PD 
n/a – no confirmation needed 
PD 
 
6.4.2. 
Secondary Efficacy Analyses 
The Duration of Response (DOR) is defined as the time between the date of first response and 
the subsequent date of objectively documented progression of disease or death. The CR or PR 
will be derived based on investigators or local radiologist assessment, as well as independent 
review. The censoring rule is shown in Table 6. 
Overall survival (OS) is defined as the time between the first dosing date and the date of death. 
Progression free survival (PFS) is defined as the time from the first dosing date to the date of the 
first documented progression or death due to any cause, whichever occurs first. The censoring 
rule is illustrated in Table 7. 
Duration of response (DOR) and PFS will be analyzed using Kaplan–Meier product-limit 
estimates. Median PFS will be presented with 2-sided 95% CI if estimable. Censoring rules 
(table 8, Table 9) is based on the Food and Drug Administration Guidance for Industry Clinical 
Trial Endpoints for the Approval of Cancer Drugs and Biologics (2007). The cumulative PFS 
will be plotted over time. OS will be analyzed similarly if data is available. 
DCR is 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. DCR will be calculated and a 
2-sided Clopper–Pearson 95% CI will be constructed. 
Summary tables and plots for the secondary endpoints based on Independent Review will be 
presented for iCCA patients by these 4 categories: with FGFR2 rearrangement, without FGFR2 
rearrangement, with FGFR2 rearrangement with GEM/CIS and without FGFRi Prior Treatment, 
with FGFR2 rearrangement with FGFRi prior treatment. 
 


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Summary tables and plots will also be presented based on data from the Investigator Review.  
 
Table 6.   Censoring Rules for Progression-Free Survival   
No. 
Situation 
 
End Date 
 
Outcome 
 
1 
Documented PD between scheduled visits a 
Date of the first assessment of the series 
of the tests that determined PD  
PFS event  
 
2 
Death during the study in absence of PD a 
Date of death  
PFS event  
3 
Patients still on treatment without PD as of 
data cut-off b 
Date of last tumor assessment c 
 
Censored  
 
4 
Treatment discontinuation for other than PD or 
death, and no post baseline tumor assessments  
Date of first dose 
 
Censored  
 
5 
Treatment discontinuation for other than PD or 
death with post baseline tumor assessments  
Date of last tumor assessment  
 
Censored  
 
6 
New anticancer treatment started before PD or 
death  
Date of last tumor assessment c  before 
start of new treatment  
Censored  
 
7 
Death or PD after two or more missed tumor 
assessments d 
Date of the last tumor assessment c before 
missed assessments  
Censored 
 
8 
No baseline or unreadable baseline assessment 
but readable post baseline assessments  
Date of first dose  
 
Censored  
 
a. 
If documented PD and/or death occurs after the last dose, it is counted as a PFS event as long as the PD and/or the 
death occurs within 21 days since the date of the last dose of study drug and provided that it does not violate other 
censoring rules (e.g. start of new anticancer therapy before the PD or death). Otherwise the patient will be censored on 
the date of last tumor assessment before the date of last dose date + 21 days.  
b. 
For PFS analysis, the date of last tumor assessment refers to the date of last adequate tumor assessment of CR, PR, SD, 
or PD.  
c. 
This refers to patients who were still receiving study treatment at time of data cutoff.  
d. 
Two or more missed tumor assessments is defined as having either one of the following two durations being longer 
than 2 cycles for the first 6 months of treatment, or thereafter 3:  
               - Duration between two consecutive tumor assessments  
               - Duration between the last tumor assessment and death or PD.  
 
Table 7. 
Censoring Rules for Overall Survival (OS) Endpoint. 
Situation 
End Date 
Outcome 
Death before cut-off 
Date of death  
Death  
Death after data cut-off  
Date of data cut-off  
Censored event  
Patient still alive at data cut-off  
Date of data cut-off  
Censored event  
Patient discontinued treatment due to any reason 
before data cut-off  
Date last known to be alive  
Censored event  
6.4.3. 
Other Efficacy Analyses  
By-patient listing to include FGFR gene status, first dose date, duration of treatment, best overall 
response, duration of response, and cancer sub-type will be presented for each cohort.  
 
For cohort 2 patients, response to therapy follows the RANO (Response Assessment in Neuro-
Oncology) criteria. The criteria are shown in Table 8 below: 


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Table 8. 
Summary of RANO Response Criteria 
Criterion 
Complete 
Response 
Partial 
Response 
Stable Disease 
Progressive 
Disease 
T1 enhancing disease 
None 
≥ 50% ↓ 
< 50% ↓ but <25% ↑ 
≥ 25% ↑a 
T2/FLAIR 
Stable or ↓ 
Stable or ↓ 
Stable or ↓ 
↑a 
New lesion 
None 
None 
None 
Presenta 
Corticosteroids 
None 
Stable or ↓ 
Stable or ↓ 
NAb 
Clinical status 
Stable or ↑ 
Stable or ↑ 
Stable or ↑ 
↓a 
Requirement for response 
All 
All 
All 
Anya 
Abbreviations: NA=not applicable, RANO = Response Assessment in Neuro-Oncology, T1 = T1 relaxation, 
T2/FLAIR = T2-weighted fluid-attenuated inversion recovery. 
a 
Progression occurs when this criterion is present. 
b 
Increase in corticosteroids alone will not be taken into account in determining progression in the absence of 
persistent clinical deterioration. 
 
The response results with RANO response criteria will be compared with the response results with 
RECIST 1.1. The best responses with the two criteria will be used and displayed in the table output. 
The patient level listing will be provided.   
6.5. 
Safety Analyses 
The population used for safety analyses will be the safety population who enrolled in the study.  
Safety will be assessed on the basis of adverse event (AE) reports, clinical laboratory data, ECG 
parameters, physical examinations, vital signs and body weight, performance status, and 
ophthalmological examination. 
6.5.1. 
Extent of Exposure 
6.5.1.1. 
Administration of Study Drug 
The number of cycles initiated and completed, extent of exposure (Treatment Duration), relative 
dose intensity in Cycle 1, relative dose intensity in all cycle and total dosage for TAS-120 will be 
summarized.  
Relative dose intensity (RDI) is defined as the ratio of the amount of drug actually administered 
to the amount planned in the study for TAS-120. The relative dose intensity is calculated in the 
following steps: 
1. Amount of drug actually administered is total number of dose administered  
2. Treatment Duration = last dose date – first dose date +1 
3. Amount of drug planned for the patient =Treatment Duration  
4. Relative Dose Intensity = (Amount of drug actually administered / Amount of drug 
planned) x 100% 
A by-patient listing of dosing of study medication will be also provided. 


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6.5.1.2. 
Modification of Study Drug 
The number and percentage of patients with at least one dose interruption along with reason for 
the interruptions will be summarized by cohort. 
The number and percentage of subjects with at least one dose reduction and reason for the dose 
reduction will be summarized. 
By-patient listings of dose interruptions and dose reductions will be also provided. 
In addition, summary tables will also be provided for the iCCA patients by the categories of: 
with FGFR2 rearrangement, without FGFR2 rearrangement, with FGFR2 rearrangement with 
GEM/CIS and without FGFRi Prior Treatment, with FGFR2 rearrangement with FGFRi prior 
treatment.  
6.5.2. 
Adverse Events 
Summary of AEs will be performed by cohort, and by these 4 categories for the iCCA patients: 
with FGFR2 rearrangement, without FGFR2 rearrangement, with FGFR2 rearrangement with 
GEM/CIS and without FGFRi Prior Treatment, with FGFR2 rearrangement with FGFRi prior 
treatment. 
6.5.2.1. 
Deaths 
All deaths will be summarized. The reasons of death will also be summarized. The reasons are 
categorized in the following terms: 
• Radiological Disease Progression 
• Clinical Disease Progression 
• Toxicity 
• Adverse Event 
• Other 
A by-patient listing of all deaths will be provided for the All Treated patients population. 
6.5.2.2. 
Serious Adverse Events 
A serious Adverse Event (SAE) is an AE which falls into one or more of the following 
categories: 
• Results in death 
• Is life-threatening 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability or incapacity 
• Is a congenital anomaly/birth defect 
• Is any other important medical event 
Serious AEs will be summarized with the following categories: 


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• Overall summary of SAEs by worst CTC grade (grade 1, 2, 3, 4, 5, unknown) presented 
by SOC/PT. 
• A summary of serious AEs, overall and by system organ class and preferred term. 
6.5.2.3. 
Adverse Events Leading to Discontinuation of Study Drug 
AEs leading to discontinuation will be summarized: 
• Overall summary of AEs leading to discontinuation by worst CTC Grade (grade 1, 2, 3, 
4, 5, any grade, Grade 3-5) presented by SOC/PT 
• Overall summary of drug-related AEs leading to discontinuation by worst CTC grade 
(Grade 1, 2, 3, 4, 5, any grade, Grade 3-5) presented by SOC/PT 
A by-patient listing of AEs leading to discontinuation will also be provided. 
6.5.2.4. 
Adverse Events Leading to Dose Modification 
AEs leading to dose modification (including dose interruption or reduction) will be summarized: 
• Overall summary of AEs leading to modification by worst CTC Grade (grade 1, 2, 3, 4, 
5, any grade, Grade 3-5) presented by SOC/PT 
• Overall summary of drug-related AEs leading to discontinuation by worst CTC grade 
(Grade 1, 2, 3, 4, 5, any grade, Grade 3-5) presented by SOC/PT 
A by-patient listing of AEs leading to modification will also be provided. 
6.5.2.5. 
Adverse Events 
An adverse event (AE) is any untoward medical condition that occurs in a patient while 
participating in this clinical study. Adverse events will be coded according to the Medical 
Dictionary for Regulatory Activities (MedDRA 18.1) terminology and the severity of the 
toxicities will be graded according to the NCI CTCAE, v4.03, where applicable.   
 
Adverse Events that occur from the initiation of TAS-120 medication administration to 30 days 
after the last dose of study medication, and do not necessarily have a causal relationship to the 
use of the study medication will be summarized.  
Number of patients with AEs will be presented by system organ class in the overall column in 
decreasing order. Within each system organ class, the number of patients with AEs will be 
displayed by preferred term (PT) in descending order.  
The following adverse event summary tables will be generated: 
1) An overall summary with the number and percentage of patients reporting AEs, serious 
AEs, grade 3 or higher AEs, treatment-related AEs, AEs leading to study treatment 
(TAS-120) discontinuation and AEs with outcome of deaths.  
In the summary, a patient is counted once at the system organ class and once at each 
preferred term within the system organ class. Additional summary by system organ class, 


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preferred term and grade (including Total and >= grade 3 categories) will also be 
generated. 
2) Study-treatment-related AEs overall and by system organ class and preferred term. 
Additional summary by system organ class, preferred term and grade (including Total 
and >= grade 3 categories) will also be generated. 
All those AEs with relationship to TAS-120 marked as “Related” or missing will be 
reported in the table.  
3) AEs by highest grade (worse severity) overall and by system organ class and preferred 
term.  
In the summary, a patient is counted once at the highest grade for which the event 
occurred in the system organ class and the highest grade for each unique preferred term 
within that system organ class. Therefore, patients may only contribute once to each 
preferred term and once to each system organ class. The missing severity grade will be 
reported in a separate category. 
4) Grade 3 or higher AEs, overall and by system organ class and preferred term 
5) Study-treatment related AEs by grade (severity), overall and by system organ class and 
preferred term 
6) AEs leading to study treatment termination, overall and by system organ class and 
preferred term. Additional summary by system organ class, preferred term and grade 
(including Total and >= grade 3 categories) will also be generated. 
7) AEs with outcome of deaths, overall and by system organ class and preferred term  
In addition, the time to onset of some special AEs of interest in the study may be summarized if 
appropriate.   
6.5.2.6. 
Adverse Events of Special Interest 
Incidence: 
Adverse event of special interest (AESI), including hyperphosphatemia, will be summarized for 
each category/subcategory: 
• Overall summary of AESI by worst CTC grade presented by category or subcategory / 
PT 
A by-patient listing of AESI will also be provided. 
Time to Onset: 
Time-to-onset of selected AESI, including hyperphosphatemia, will be graphically displayed for 
each category/subcategory of AESI using the Kaplan-Meier technique: 
• Time to AESI (grade 1 and above)    


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• Time to AESI of Grade ≥3  
Time to Resolution: 
Time-to-resolution of selected AESI, including hyperphosphatemia, will be summarized 
separately for each category / subcategory: 
• Time to resolution of AESI of Grade ≥3  
Time-to-resolution analyses are restricted to treated patients who experienced the specific events.  
The following summary statistics will be reported: percentage of subjects who experienced the 
specific events, percentage of subjects with resolution of the longest AESI, median time-to 
resolution along with 95% CI (derived from Kaplan-Meier estimation, if estimable) and ranges. 
6.5.2.7. 
Multiple Adverse Events  
The following summary tables will be provided: 
• Total number and rate (exposure adjusted) of occurrences for all AEs.  
• For AESI: number of subjects experiencing an AESI once or multiple times  
The exposure adjusted incidence rate per X patient time is calculated as X×Y× (total number of 
unique AEs)/(total exposure time), where: 
 X = user-specified time factor, X= 1000 or 100   
 Y = 365.25 for years or Y = 30.4375 for months 
Listing displaying the unique instances of all AEs (that is, after duplicates have been eliminated 
and overlapping and contiguous occurrences of the same event (same PT) have been collapsed) 
will be provided. 
6.5.3. 
Clinical Laboratory Evaluations 
Clinical laboratory results will be summarized using SI units. Laboratory measurements will be 
summarized for all protocol scheduled time points for all patients in the safety population. 
Descriptive (n, mean, STD, median, min and max) statistics will be presented for all clinical 
chemistry, hematology and coagulation laboratory parameters at each scheduled visit. Change 
from baseline at each scheduled post-baseline visit will also be presented. 
Patient counts and percentages of patient for each category of each urinalysis parameters will be 
summarized at each scheduled visit. 
Shift tables will be presented for each laboratory parameter to display the shift from baseline to 
the maximum post-baseline CTCAE grade (v4.03). Summary tables will be provided presenting 
the count and percentage of patients for each laboratory test by the maximum post-baseline 
CTCAE grade reported. All post-baseline assessments (including unscheduled visits) will be used 
to determine the maximum (worst) post-baseline CTCAE grade. Time to maximum Grade 3/4 and 


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time to resolution (return to grade <2 or baseline grade or below) may be summarized as 
appropriate. 
Any laboratory abnormality that has a clinical impact on the patient, eg, results in delay of study 
drug 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 < 1000/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 CTCAE grade criteria (Version 4.03). 
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 another anticancer 
treatment is started. 
A baseline laboratory value will be defined as the last assessment performed on or prior to the date 
and time of first dose of study treatment. Laboratory test results will be categorized by CTCAE 
criteria V4.03. 
Estimated creatinine clearance (CLcr) will be calculated using baseline creatinine value according 
to the following formula. 
 
All clinical laboratory data will be presented in patient level listings. 
The laboratory tests among Hematology and Coagulation, Serum chemistry, and Urinalysis are 
listed in table 9.  
 
Table 9.  
Laboratory Tests 
Assessment 
Test Items 
Hematology and 
Coagulation 
Red blood cell count, hemoglobin, hematocrit, platelets, white blood cell count with 
differential, neutrophils, lymphocytes, monocytes, eosinophils,  basophils, 
International normalized ratio (INR), Activated partial thromboplastin time (APTT)  
Serum chemistry 
Aspartate aminotransferase (AST), alanine aminotransferase (ALT), ALP, total 
bilirubin, glucose, creatinine clearance, blood urea nitrogen(BUN) or urea, 
phosphorus, calcium, chloride, sodium, potassium, creatine kinase (CK), creatinine 
kinase MB (CK-MB), Troponin I, Troponin T 
Urinalysis 
Urine protein, glucose, urine density 
Other 
• 
Neutrophils includes both segmented and band neutrophils 
• 
creatinine clearance includes calculated (Ccr) or measured creatinine clearance 
CCI


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6.5.3.1. 
Additional Safety Analyses 
6.5.3.1.1. Ophthalmological Examination 
Ophthalmological examination will be performed at screening (within 28 days prior to study 
medication administration on Day 1 of Cycle 1), 4-6 weeks after starting treatment with TAS-120, 
End of treatment visit, and 30-day safety follow-up. Ophthalmological examination results will be 
summarized and listed. 
6.5.3.1.2. Neurological Examination 
The neurological examination will be obtained at screening within 28 days prior to TAS-120 
administration on Day 1 of cycle 1, other time due to local requirements or physician judgement, 
end of treatment visit, and 30-day safety follow-up visit. The examination results will be listed. 
6.5.4. 
Vital Signs 
Vital sign measurements including systolic blood pressure, diastolic blood pressure, pulse rate, 
respiration rate, and temperature at each scheduled and changes from baseline in vital sign 
measurements will be summarized with descriptive statistics at each scheduled time point.  
Weight at each scheduled time and changes from baseline will be summarized with descriptive 
statistics at each scheduled time point for the safety population. Weight will be displayed in 
kilograms, height, collected only at baseline, will be displayed in centimeters, and temperature will 
be displayed in Celsius. The safety population will be used. 
All vital signs data will be presented in a listing. 
6.5.5. 
 Electrocardiograms 
The results of the read 12-lead ECG at each scheduled will be summarized by the categories 
Normal; Abnormal, not clinically significant; and Abnormal, clinical significant. If two ECG 
measurements are collected during one visit, the worst category will be used in the summary. 
The safety population will be used. 
A summary of interval duration measurements at each cycle and change from baseline will be 
summarized with descriptive statistics at each scheduled time point. QTcF result values will be 
categorized as follows: <=470 msec, >470 and <=480 msec, >480 and <=500 msec, >500 msec.  
A summary of the frequency of QTcF interval result and change from baseline categories will be 
generated by visit. The change from baseline categories defined as: QTc interval increase from 
baseline <= 30 msec; QTC interval increases from baseline 30 -  60 msec; QTc interval increases 
from baseline > 60 msec: If two ECG measurements are collected during one visit, the mean 
measurement will be used in the summary. 
The 12-lead, resting ECGs will be obtained to explore the relationship between the plasma 
concentration of TAS-120 and QTc prolongation. 


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6.5.6. 
Physical Examination 
All physical examination will be performed 24 hours prior to TAS-120 administration on day 1 
beginning with cycle 2. The baseline screening measurement of physical examination will be taken 
on screening within 28 days prior to TAS-120 administration on Day 1 of Cycle 1. The physical 
examination will also obtain at the End of Treatment Administration, and 30-day safety follow-up 
visit. 
The physical examination data will be presented in a patient level listing. 
6.5.7. 
ECOG Performance Status 
The ECOG performance status score will be obtained at the following time points: screening, and 
24 hours prior to TAS-120 on day 1 beginning with cycle 2, the End of Treatment Administration, 
and 30-day safety follow-up visit. The ECOG performance status scores and the grades from 0 to 
5 is described in the following table: 
Table 10. 
Grade Categories of Eastern Cooperative Oncology Group Score 
GRADE 
ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, eg, light house work, office work. 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities.  Up 
and about more than 50% of waking hours. 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours. 
4 
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or chair. 
5 
Dead. 
The change from Day 1 in Cycle 1 in the ECOG performance status scores will be presented in a 
shift table. A patient level listing will also presented. 
6.5.8. 
Pregnancy Test 
If the patient is female and of child bearing potential, a serum or urine beta-human chorionic 
gonadotropin (β-HCG) pregnancy test will be performed 7 days prior to the first administration 
of the study drug. Pregnancy test result will be listed. 
6.6. 
Other Analyses 
The Quality of Life data is not collected in the Phase I Expansion study.   
CCI


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6.8. 
Pharmacokinetic Analyses 
6.8.1. 
Optional Pharmacokinetic Samples 
Optional blood PK samples will 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). 
Kp (TAS-120 concentration ratio of CSF to plasma) will be calculated as follows:  
Kp = CSF concentration / Plasma concentration at the same time. 
For patients whose CSF sample was collected, the summary Table for plasma and CSF 
concentrations and Kp value will be provided.  
A patient level listing for plasma, CSF concentrations and Kp values will be provided. 
6.8.2. 
Pharmacokinetic Blood Samples 
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 summary table and subject level listing for plasma concentration will be provided. 


Taiho Oncology, Inc. 
 
 
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36 
 
 
  
 
7. 
CHANGES IN PLANNED ANALYSIS 
The following table summarizes substantive changes made to the SAP in the current Amendment 
1;  
Section 
Description of Change  
Brief Rationale 
Section 4.1 
Summary of Study 
Design 
Text was amended as follows: 
Group 1 (Enrollment suspended as of 
Amendment 7): Patients with 
intrahepatic or extrahepatic CCA 
harboring FGFR2 gene fusions or 
rearrangements. 
Group 2: Patients with intrahepatic or 
extrahepatic CCA harboring FGFR2 
gene fusions or rearrangements that 
have not received or received less than 1 
cycle of prior chemotherapy (due to 
intolerance or patient refusal) 
Group 3 (Enrollment suspended as of 
Amendment 7): CCA (iCCA or eCCA) 
with FGFR2 gene fusions or 
rearrangements treated with prior FGFR 
inhibitors 
 
In order to be consistent with the 
protocol. 
Section 5.4 
Timing of Analysis 
The following text was amended as 
follows:  
The final analysis will be performed 
when at least 90% of all treated 
patients had approximately 4 months 
of follow-up.  
 
In order to be consistent with 
patients’ follow-up time. 
 


Taiho Oncology, Inc. 
 
 
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37 
 
 
  
 
8. 
DEFINITIONS AND CONVENTIONS FOR DATA HANDLING 
8.1. 
Baseline Period 
Baseline evaluations or events are defined as evaluations or events that occur before the date and 
time of first dose of study treatment.  
If the onset time of event or evaluation time or dosing time is missing or not collected, the 
following definitions will be applied: 
• Pre-treatment AEs will be defined as AEs with an onset date prior to but not including the 
day of the first dose of study treatment 
• Baseline evaluations (laboratory tests, vital signs) will be defined as evaluations with a 
date on or prior to the day of first dose of study treatment 
If there are multiple valid assessments, the assessment that is closest to day (and time if 
collected) prior to the first dose of study treatment will be used as the baseline in the analyses. If 
multiple assessments are collected at the same date (and time if collected), the assessment with 
the latest database entry date (and time if collected) will considered as baseline. 
8.2. 
Post-Baseline Period 
On-treatment AEs will be defined as AEs with an onset date and time on or after the date-time of 
the first dose of study drug (or with an onset date on or after the day of first dose of study 
treatment if time is not collected or is missing). An AE will be counted as on-treatment if the 
event occurred within 30 days of the last dose of study treatment. 
On-treatment evaluations (laboratory tests, vital signs) will be defined as evaluations taken after 
the day (and time, if collected and not missing) of first dose of study treatment. An evaluation 
will be counted as on-treatment if it occurred within 30 days of the last dose of study treatment. 
8.3. 
AESI Definition and Conventions 
The AESI consist of a list of preferred terms grouped by specific category (for example, 
pulmonary events, gastrointestinal events categories) and/or by subcategory (for example, 
diabetes). These categories and subcategories are defined based on MedDRA, and the list that is 
most current at the time of analysis will be used.  Also changes may be made to this list with 
each new version of MedDRA. 
8.4. 
Time-to-Onset Definition 
Time-to-onset of AESI (any grade) for a specific category (for example, pulmonary events, 
gastrointestinal events) is defined as the time between the day of the first dose of study treatment  
and the onset date of the earliest AESI (of any grade) in this category. 
If the subject did not experience an AESI (of any grade) in the category, time-to-onset will be 
censored at the maximum follow-up time of all subjects in their respective treatment group (that 
is, for subjects without an event, follow-up time is defined from first dosing date up to last 
dosing date +30 days if subjects are off treatment and followed for at least 30 days, otherwise it 


Taiho Oncology, Inc. 
 
 
Statistical Analysis Plan (Phase I Expansion)– Protocol: TPU-TAS-120-101 
   25 OCT 2019 
 
 
38 
 
 
  
 
is defined up to the last known alive date). The resulting Kaplan-Meier plot will represent the 
cumulative rate of the AESI (any grade) in the category over time. 
Time-to onset of AESI (Grade 3-5) for a specific category is defined similarly but restricted to 
Grade 3-5 AESI. 
Time-to onset of drug-related (Grade 3-5 or any grade) AESI for a specific category is defined 
similarly but restricted to drug-related AESI. 
Time-to onset for a specific subcategory is defined similarly but restricted to events in this 
subcategory. 
8.5. 
Time-to-Resolution Definition 
In order to derive the time-to-resolution, overlapping or contiguous AESI within a specific 
category will be collapsed into what will be termed “clustered” AESI.  For example, if a subject 
(without pre-treatment AE) experienced an AE from 01 January to 05 January, another AE (with 
different PT but within same category) from 06 January to 11 January, and the same AE from 10 
January to 12 January, these will be collapsed into one clustered AESI from 01 January to 12 
January. Table 11 summarizes key derivation steps for each type of clustered select AEs. 
Algorithm for collapsing multiple records of adverse event is summarized in section 8.6.  
Time-to-resolution of AESI (any grade) for a specific category is defined as the longest time 
from onset to complete resolution or improvement to the grade at baseline among all clustered 
AESI in this category experienced by the patient. Events which worsened into Grade 5 events 
(death) or have a resolution date equal to the date of death are considered unresolved. If a 
clustered AESI is considered to be unresolved, the resolution date will be censored to the last 
known date alive. Improvement to the grade at baseline implies that all different AE events in the 
clustered AESI should at least have improved to the corresponding (that is, with same preferred 
term) baseline grade. This measure is defined only for subjects who experienced at least one 
AESI in the specific category. 
The time-to-resolution of AESI (Grade 3-5) for a specific category is defined similarly with an 
onset date corresponding to a Grade 3-5 AESI. 
Time-to-resolution of drug-related AESI (any grade or Grade 3-5) is defined similarly but 
restricted to drug-related AESI. 
Time-to-resolution for a specific subcategory is defined similarly but restricted to events of this 
subcategory. 
Table 11: 
Derivation of Clustered AESI 
Type of clustered select AE 
Derivation 
Any grade 
Collapse any on-treatment AESI from the same 
category 
 
Drug-related of any grade 
Collapse any on-treatment drug-related 
AESI from the same category 
 


Taiho Oncology, Inc. 
 
 
Statistical Analysis Plan (Phase I Expansion)– Protocol: TPU-TAS-120-101 
   25 OCT 2019 
 
 
39 
 
 
  
 
Type of clustered select AE 
Derivation 
Grade 3-5 
Collapse any on-treatment AESI from the same 
category. 
Resolution will be based on the onset date of the earliest 
Grade 3-5 records  (if no Grade 3-5 record, clustered 
AESI is excluded) 
Drug-related of Grade 3-5 
Collapse any on-treatment drug-related AESI from the 
same category.  Resolution will be based on the onset 
date of  the earliest Grade 3-5 record (if no Grade 3-5 
record, clustered AESI is excluded) 
 
Abbreviations: AE=adverse event; AESI=adverse event of special interest. 
8.6. 
Multiple Adverse Events 
The algorithm for collapsing multiple records of select adverse event is using the following 
conventions.  For each patient and specified category, the corresponding adverse event records 
will be collapsed when: 
Multiple adverse event records have the same onset date. 
The onset date of an event record is either the same day or 1 day later than the resolution date of 
a preceding event record (contiguous events). 
The onset date of an event record is after the onset date and prior to or on the resolution date of a 
preceding event record (overlapping events). 
8.7. 
Other Data Handling Rules 
Missing data will not be imputed in the patient level listings.  The listings will only present the 
data recorded on the original CRF.  
If an AE has a completely missing onset date, the AE will be included in the AE summary tables. 
A medication with a completely missing start date is considered a prior medication. A 
medication with a completely missing stop date is considered a concomitant medication.  
If an adverse event or a medication has a partial missing start or stop date, the following rules 
will be used to determine whether it is an AE for the AE summary tables, or a prior or 
concomitant medication.  
Table 12. Partial Date Imputation Rule for AE or Medication  
Partial Missing Start or 
Stop Date 
Derived Start Date 
Imputed Stop Date 
Missing month and day, 
and the year  is present 
 
January 1 of that year or first dose 
date if the year is the same as the 
year of  first dose date 
December 31 of that 
year 
Missing day, but year and 
month are present 
First day of that month or first 
dose date if the year and month are 
Last day of that month 


Taiho Oncology, Inc. 
 
 
Statistical Analysis Plan (Phase I Expansion)– Protocol: TPU-TAS-120-101 
   25 OCT 2019 
 
 
40 
 
 
  
 
Partial Missing Start or 
Stop Date 
Derived Start Date 
Imputed Stop Date 
 
the same as the year and month of 
first dose date 
Missing month, but year 
and day are present 
Missing month derived as January 
or same as first dose month if the 
year is same as the year of first 
dose.  
Missing month imputed 
as December 
 
The above rule is also used for determining the cycles of adverse events and concomitant 
medications.  
 
The derived date is only used for determining AEs, cycle of adverse events and concomitant 
medications.  The collected partial dates will be reported in the listings.    
 
For the medical history, prior surgery, prior radiotherapy, and prior systemic cancer therapies: 
• 
Missing day and month - January 1 will be assigned to the missing fields. 
• 
Missing month only - Treat day as missing and replace both month and day according 
to the above procedure. 
• 
Missing day only - Assign first of the month to the missing day. 
 
Partially missing stop dates for the types of data listed above will be imputed as: 
• 
year is missing, no imputation. Date left missing. 
• 
month is missing and year is prior to year of first dose of study medication- impute 
'December'. 
• 
month is missing and year the same as the year of the first dose of study medication – 
impute same month as in start date of study medication. 
• 
day is missing, impute 'last date of that month'. If results in a date ≥ the date of the 
first dose of study medication impute day as the day prior to the first dose of study 
medication. 


Taiho Oncology, Inc. 
 
 
Statistical Analysis Plan (Phase I Expansion)– Protocol: TPU-TAS-120-101 
   25 OCT 2019 
 
 
41 
 
 
  
 
9. 
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 
fusions as a target for treating cholangiocarcinoma. Current Opinion in Gastroenterology, 
31(3), 264–268.  
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 
cancer treatment-induced diarrhea. J Clin Oncol. 2004 Jul 15;22(14):2918-26. 
16. Kris MG, Hesketh PJ, Somerfield MR, et al. American Society of Clinical Oncology 
guidelines for antiemetics in oncology: update 2006. J Clin Oncol. 2006 Jun 20;24:2932-47. 
17. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid 
tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. 


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   25 OCT 2019 
 
 
42 
 
 
  
 
18. Barker FG, 2nd, Chang SM, Gutin PH, et al. Survival and functional status after resection of 
recurrent glioblastoma multiforme. Neurosurgery. 1998;42:709–20. 
19. Gallego O. Nonsurgical treatment of recurrent glioblastoma. Curr Oncol. 2015 Aug;22(4): 
e273–e281. 
20. Picca A, Berzero G, Bielle F, et al. FGFR1 actionable mutations, molecular specificities, and 
outcome of adult midline gliomas. Neurology. 2018;90:e2086-94. 
21. Lasorella A, Sanson M, Iavarone A. FGFR-TACC gene fusions in human glioma. Neuro- 
Oncology. 2017;19: 475-83. 
22. Pearson A, Smyth E, Babina IS. High-level clonal FGFR amplification and response to 
FGFR inhibition in a translational clinical trial. Cancer Discov. 2016;6: 838-51. 
 


Taiho Oncology, Inc. 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101                        15 October 2020 
STATISTICAL ANALYSIS PLAN
VERSION: 2.0
DATE OF PLAN: 15 October 2020
PROTOCOL NUMBER:
TPU-TAS120-101 
STUDY TITLE:
PHASE 1/2 STUDY OF TAS-120 IN PATIENTS WITH ADVANCED SOLID TUMORS 
HARBORING FGF/FGFR ABERRATIONS (PHASE 2) 
SPONSOR:
Taiho Oncology, Inc. 
101 Carnegie Center 
Princeton, NJ USA 08540 
+1 (609) 750-5300 
This trial was conducted in accordance with the ethical principles of Good Clinical Practice 
(GCP), according to the International Conference on Harmonization (ICH) Harmonized 
Tripartite Guideline.
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or 
confidential and may not be disclosed unless such disclosure is required by applicable law or regulations. 
In any event, persons to whom the information is disclosed must be informed that the information is privileged 
or confidential and may not be further disclosed by them.  These restrictions on disclosure will apply equally to 
all future information supplied to you that is indicated as privileged or confidential. 
1 


Tai h o O nc ol o g y, I nc. 
 
Statistical A nal ysis Pla n ( P hase 2) – Pr ot oc ol T P U - T A S 1 2 0- 1 0 1                        1 5 Oct o ber 2 0 2 0 
S T A TI S TI C A L A N A L Y SI S P L A N  
V er si o n 2 . 0 
 
A P P R O V A L P A G E  
 
P H A S E ½ S T U D Y I N P A TI E N T S WI T H A D V A N C E D S O LI D T U M O R S 
H A R B O RI N G F G F/ F G F R A B E R R A TI O N S ( P H A S E 2) 
 
Pr ot o c ol T P U -T A S -1 2 0 -1 0 1  
 
 
Pr e p ar e d b y:  
 
 
 
 
Si g n at ur e  
 
D at e  
 
 
A p pr o v e d b y:  
 
 
 
 
 
Si g n at ur e  
 
D at e  
 
 
 
 
 
Si g n at ur e  
 
D at e  
 
 
 
 
 
 
2 
O ct 1 5, 2 0 2 0
O ct 1 5, 2 0 2 0
O ct 1 6, 2 0 2 0
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D


Tai h o O nc ol o g y, I nc. 
 
Statistical A nal ysis Pla n ( P hase 2) – Pr ot oc ol T P U - T A S 1 2 0- 1 0 1 
1 5 Oct o ber 2 0 2 0  
T A B L E O F C O N T E N T S 
1.  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F  T E R M S ............................... 7 
2.  
I N T R O D U C TI O N ........................................................................................................ 9 
3.  
S T U D Y O BJ E C TI V E S A N D  E N D P OI N T S  .............................................................. 1 0 
3. 1.  
St u d y O bjecti ves  ......................................................................................................... 1 0 
3. 1. 1.  
Pri mar y O bj ecti ve  ....................................................................................................... 1 0 
3. 1. 2.  
Sec o n dar y O bj ecti ves  ................................................................................................. 1 0 
3. 2.  
St u d y E n d p oi nts  .......................................................................................................... 1 0 
3. 2. 1.  
Pri mar y E n d p oi nt ........................................................................................................ 1 0  
3. 2. 2.  
Sec o n dar y E n d p oi nts .................................................................................................. 1 0  
4.  
S T U D Y D E S C RI P TI O N  ............................................................................................ 1 2 
4. 1.  
S u m mar y of St u d y Desi g n .......................................................................................... 1 2  
4. 2.  
Treat me nt Assi g n me nt a n d Bli n di n g/ U n bli n di n g ....................................................... 1 8  
4. 3.  
Det er mi nati o n of Sa m ple Size .................................................................................... 1 8 
5.  
S T U D Y P E RI O D S, T R E A T M E N T R E GI M E N S, A N D P O P U L A TI O N S 
F O R A N A L Y SI S  ........................................................................................................ 1 9 
5. 1.  
St u d y Peri o ds .............................................................................................................. 1 9  
5. 2.  
Treat me nt Re gi me ns  ................................................................................................... 1 9 
5. 3.  
P o p ulati o ns f or A nal ysis ............................................................................................. 1 9  
5. 4.  
Ti mi n g of A nal ysis  ..................................................................................................... 1 9 
6.  
S T A TI S TI C A L A N A L Y SI S  ...................................................................................... 2 0 
6. 1.  
Ge ner al Met h o ds  ......................................................................................................... 2 0 
6. 2.  
St u d y C o n d u ct ............................................................................................................ 2 0  
6. 2. 1.  
Accr u al  ........................................................................................................................ 2 0 
6. 2. 2.  
Pr ot oc ol De viati o ns .................................................................................................... 2 1  
6. 3.  
St u d y P o p ulati o n ......................................................................................................... 2 1  
6. 3. 1.  
Patie nt Dis p ositi o n  ...................................................................................................... 2 1 
6. 3. 2.  
De m o gra p hic a n d Ot her Baseli ne C haracteristics  ...................................................... 2 1 
6. 3. 3.  
Me dical Hist or y  .......................................................................................................... 2 2 
6. 3. 4.  
Pri or/ C o nc o mita nt T hera p y a n d T hera pies ................................................................. 2 2  
6. 3. 4. 1.  
Pri or A ntica ncer T her a p y  ........................................................................................... 2 3 
6. 3. 4. 2.  
Ot her Pri or/ C o nc o mita nt T hera p y .............................................................................. 2 3  
 
3 
C CI


Tai h o O nc ol o g y, I nc. 
 
Statistical A nal ysis Pla n ( P hase 2) – Pr ot oc ol T P U - T A S 1 2 0- 1 0 1 
1 5 Oct o ber 2 0 2 0  
6. 4.  
Efficac y A nal yses  ....................................................................................................... 2 3 
6. 4. 1.  
Pri mar y Efficac y A nal ys es  ......................................................................................... 2 3 
6. 4. 2. 1.  
Se nsiti vit y A nal ys es  .................................................................................................... 2 6 
6. 4. 3.  
S u b gr o u p A n al ys es ..................................................................................................... 2 6  
6. 5.  
Safet y A nal yses  .......................................................................................................... 2 6 
6. 5. 1.  
E xte nt of E x p os ure ..................................................................................................... 2 7  
6. 5. 1. 1.  
A d mi nistrati o n of St u d y Dr u g  .................................................................................... 2 7 
6. 5. 1. 2.  
M o dificati o n of St u d y Dr u g ........................................................................................ 2 7  
6. 5. 2.  
A d verse E v e nts  ........................................................................................................... 2 7 
6. 5. 2. 1.  
Deat hs  ......................................................................................................................... 2 7 
6. 5. 2. 2.  
Seri o us A d verse E v e nts .............................................................................................. 2 7  
6. 5. 2. 3.  
A d verse E v e nts Le a di n g t o Disc o nti n uati o n of St u d y Dr u g ...................................... 2 8  
6. 5. 2. 4.  
A d verse E v e nts Lea di n g t o D ose M o dificati o n .......................................................... 2 8  
6. 5. 2. 5.  
A d verse E v e nts  ........................................................................................................... 2 8 
6. 5. 2. 6.  
A d verse E v e nts of S peci al I nt erest  ............................................................................. 3 0 
6. 5. 2. 7.  
M ulti ple A d verse E ve nts ............................................................................................ 3 1  
6. 5. 3.  
Cli nical La b or at or y E val uati o ns ................................................................................. 3 1  
6. 5. 4.  
Vital Si g ns  .................................................................................................................. 3 3 
6. 5. 5.  
Electr ocar di o gra ms  ..................................................................................................... 3 4 
6. 5. 6.  
P h ysical E x a mi nati o n  ................................................................................................. 3 4 
6. 6.  
Patie nt Re p orte d O utc o m es ( P R O)  ............................................................................. 3 5 
6. 6. 1.  
E Q - 5 D ......................................................................................................................... 3 6 
6. 6. 2.  
E O R T C Q L Q - C 3 0 ...................................................................................................... 3 6 
6. 7. 1.  
P K A nal ysis  ................................................................................................................ 3 8 
6. 8.  
I nteri m A nal yses ......................................................................................................... 3 8 
7.  
D E FI NI TI O N S A N D C O N V E N TI O N S F O R D A T A H A N D LI N G  ......................... 3 9 
7. 1.  
Baseli ne Peri o d  ........................................................................................................... 3 9 
7. 2.  
P ost- Baseli ne Peri o d  ................................................................................................... 3 9 
7. 3.  
A E SI D efi niti o n a n d C o n ve nti o ns .............................................................................. 3 9  
7. 4.  
Ti me -t o-O nset Defi niti o n  ........................................................................................... 3 9 
7. 5.  
Ti me -t o- Res ol uti o n Defi niti o n ................................................................................... 4 0 
7. 6.  
M ulti ple A d verse E ve nts ............................................................................................ 4 1  
 
4 
C CI


Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020  
7.7. 
Other Data Handling Rules .........................................................................................41 
8. 
REFERENCES ...........................................................................................................44 
9. 
REVISION HISTORY ...............................................................................................45 
 
 
5 


Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020  
LIST OF TABLES 
Table 1. Study Schedule for Phase 2 
Table 2. Observed ORR with Exact 95% Confidence Interval 
Table 3. Definition of Study Periods 
Table 4. Overall Response Assessment with Target/Non-target Lesion and New Lesions 
Table 5. Confirmation Rules for Overall Response of PR and CR 
Table 6.  Censoring Rules for Progression-Free Survival 
Table 7. Censoring Rules for Overall Survival (OS) 
Table 8. Hyperphosphatemia Toxicity Grading based on serum phosphate levels as specified in 
Protocol  
Table 9. Hyperphosphatemia Toxicity Grading per CTCAE v5.0 and derivation criteria  
Table 10. Laboratory Tests 
Table 11. Grade Categories of Eastern Cooperative Oncology Group Score 
Table 12.  Time Windows for EQ-5D and EORTC-QLQ-C30 Assessment 
Table 13. Derivation of Clustered AESI 
Table 14. Partial Date Imputation Rule for TEAE or Medication 
Table 15. List of changes from Version 1.0 
 
 
 
 
 
 
6 


Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020  
1. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
Abbreviation  
Term 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
ATP 
Adenosine triphosphate 
BUN 
Blood urea nitrogen 
CCA 
Cholangiocarcinoma 
Ccr 
Calculated creatinine clearance  
CI 
Confidence interval 
CK 
Creatine kinase 
CK-MB 
Creatine kinase (isoform heart muscle) 
CR 
Complete response 
CSF 
Cerebrospinal fluid 
CTCAE 
Common Terminology Criteria for Adverse Events 
ctDNA 
Circulating tumor DNA 
CYP 
Cytochrome P450 
DCR 
Disease control rate 
DOR 
Duration of response 
eCCA 
Extra-hepatic cholangiocarcinoma 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EOT 
End-of-treatment 
EP 
Early progression 
EPR 
Early progression rate 
FFPE  
Formalin fixed paraffin embedded 
FGF 
Fibroblast growth factor 
FGFR 
Fibroblast growth factor receptor 
GCP 
Good Clinical Practice 
iCCA 
Intra-hepatic cholangiocarcinoma 
ICH 
International Council for Harmonisation 
INR 
International normalized ratio 
MedDRA 
Medical Dictionary for Regulatory Activities 
ms 
Milliseconds 
MTD 
Maximum tolerated dose 
NCI 
National Cancer Institute 
PFS 
Progression-free survival 
PK 
Pharmacokinetic(s) 
PR 
Partial response 
 
7 


Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020  
Abbreviation  
Term 
PROs 
Patient-Reported Outcomes 
PT 
Preferred term 
QD 
Once daily (continuous) dosing 
QTcF 
Fridericia’s corrected QT interval  
RECIST 
Response Evaluation Criteria in Solid Tumors 
RP2D 
Recommended Phase 2 dose 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Stable disease 
SOC 
System Organ Class 
WHO 
World Health Organization 
WOCBP 
Women of child-bearing potential 
 
 
8 


Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020  
2. 
INTRODUCTION 
The purpose of this statistical analysis plan (SAP) is to describe the planned analyses and data 
displays to be included in the Clinical Study Report (CSR) for the Phase 2 portion of Protocol 
TPU-TAS120-101. 
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%). 
Fibroblast growth factor/fibroblast growth factor receptor aberrations are a reported genetic 
modification in CCA. In iCCA, FGFR2 gene fusions which are present in an estimated 10% to 
20% of patients,1,2,3  have been identified as an early driver of oncogenic events.  Therefore, 
inhibiting the FGFR pathway in patients with iCCA is a plausible therapeutic strategy for 
appropriately selected patients with this disease.   
TAS-120 (Futibatinib) is a novel selective and irreversible small molecule FGFR inhibitor that 
equally inhibited all 4 subtypes of FGFR and showed high selectivity for FGFR when tested 
against a panel of 296 kinases, as in preclinical studies.  During the Phase 1 Dose Escalation part 
of this study, dose levels of 4, 8, 16, 20 and 24 mg QD were evaluated, where 24 mg was 
determined as the DLT dose level, and 20 mg QD was determined as the maximum tolerated dose 
(MTD) and RP2D. The Phase 1 Expansion part of the study included a total of 8 treatment groups 
enrolling different patient populations, including a group of patients with iCCA. The Phase 2 
portion of the study is to confirm and assess the efficacy and safety of TAS-120 on patients who 
have been diagnosed with iCCA harboring FGFR2 gene fusions or other FGFR2 rearrangements.  
 
 
 
9 


Tai h o O nc ol o g y, I nc. 
 
Statistical A nal ysis Pla n ( P hase 2) – Pr ot oc ol T P U - T A S 1 2 0- 1 0 1 
1 5 Oct o ber 2 0 2 0  
3.  
S T U D Y O B J E C TI V E S  A N D  E N D P OI N T S  
3. 1.  
St u d y O bjecti ves  
3. 1. 1.  
Pri m ar y O bjecti ve  
•  T o  c o nfir m  O R R  i n  i C C A  patie nts  wit h F G F R 2  ge ne  f usi o ns  or  ot her F G F R 2  
rearra n ge m e nts base d o n i n de pe n de nt ce ntral ra di ol o g y re vi e w.  
3. 1. 2.  
Sec o n d ar y O bjecti ve s 
•  T o e val uate D O R  
•  T o e val uate t he s afet y a n d t olera bilit y of T A S - 1 2 0 
•  T o e val uate D C R, P F S, a n d O S 
•  T o e val uate Patie nt -Re p orte d O utc o mes ( P R Os)  
3. 2.  
St u d y E n d p oi nts  
3. 2. 1.  
Pri m ar y E n d p oi nt  
O bjecti ve r es p o nse r ate ( O R R) acc or di n g t o R E CI S T 1. 1 g ui deli nes 4. O bj ecti ve res p o nse rate is 
defi n e d as t he pr o p orti o n of patie nts  w h o ha d best o verall res p o nse ( B O R) of C R or P R base d o n 
i n de pe n de nt ce ntral ra di ol o g y re vi e w. 
3. 2. 2.  
Sec o n d ar y E n d p oi nt s 
•  D urati o n of res p o ns e ( D O R) 
D urati o n of res p o nse is defi ne d as t he ti me  fr o m t he first d oc u me nte d res p o nse ( C R or PR) 
t o t he first d oc u me nte d o bjecti ve pr o gressi ve disease ( P D) or d eat h d ue t o a n y ca use .  
•  Disease c o ntr ol rate ( D C R)  
Disease c o ntr ol r ate is defi n e d as t h e pr o p orti o n of patie nts  wit h o bjecti ve e vi de nce of C R, 
P R, or S D, e x ce pt t hat t here is n o re q uire me nt f or a c o nfir mati o n of a n S D res p o nse. 
•  Pr o gr essi o n- fr ee s ur vi val ( P F S) 
P F S is defi ne d as t h e ti me fr o m t h e first d osi n g date t o t he d ate of t he first d oc u me nte d 
pr o gressi o n or deat h d ue t o a n y ca use, w hic he ver occ urs first.  
•  O verall s ur vi val ( O S) 
O S is defi ne d as t he ti me bet wee n t he first d osi n g date a n d t he d ate of deat h.  
O R R,  D O R,  D C R  a n d  P F S  e n d p oi nts  w ill  be  calc ulate d  b ase d  o n  I R C a n d  bas e d  o n 
i n vesti gat or assess me nt 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020  
• Safety and Tolerability of TAS-120 
Safety will be analyzed through the incidence of death, adverse event, concomitant 
medications, physical examination, vital sign measurements, clinical laboratory results, 
ECG results, ECOG performance status, and other safety observations at the time points 
indicated in the Study Schedule of Assessments (Table 1) will be monitored and recorded. 
The data will be summarized. 
• Patient-Reported Outcomes (PROs) 
EQ-5D 
The EQ-5D descriptive system comprises the following 5 dimensions: mobility, self-care, 
usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no 
problems, some problems, severe problems. Once the data have been collected and a 
database created, a scoring function can be used to assign a value (i.e., EQ-5D index score) 
to self-reported health states from a set of population-based preference weights.  
The EQ VAS records the patient’s self-rated health state on a 100-point vertical, visual 
analogue scale (0 = worst imaginable health state; 100 = best imaginable health state). 
EORTC QLQ-C30 
Health-related quality of life (HRQoL) will be assessed using the European Organization 
for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire Version 3. It is 
a 30-item instrument that has gained wide acceptance in oncology clinical studies. The 
EORTC QLQ-C30 is composed of multi-item and single scales. These include five 
functional scales (physical, role, emotional, social, and cognitive), three symptom (fatigue, 
nausea and vomiting, and pain) and a global health status/QOL scale and six single items 
(dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). All 
scales and single items meet the standards for reliability. The reliability and validity of the 
questionnaire is highly consistent across different language-cultural groups. Except for the 
overall health status and global quality of life items, responses for all items are 4-point 
categorical scales ranging from 1 (Not at all) to 4 (Very much). The overall health 
status/quality of life responses are 7-point Likert scales. 
 
11 


Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020  
4. 
STUDY DESCRIPTION 
4.1. 
Summary of Study Design 
This is an open-label, nonrandomized, Phase 2 study of TAS-120 (Futibatinib), evaluating the 
efficacy, safety, tolerability, PK and antitumor activity of TAS-120 in patients with Intra-hepatic 
cholangiocarcinoma (iCCA) with FGFR2 gene fusions or other FGFR2 rearrangements who have 
failed all standard therapies or for whom standard therapy does not exist.  
The overall study design is described in Figure 1. Study schedule for this phase 2 study is presented 
in Table 1.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Tai h o O nc ol o g y, I nc. 
 
Statistical A nal ysis Pla n ( P hase 2) – Pr ot oc ol T P U - T A S 1 2 0- 1 0 1 
1 5 Oct o ber 2 0 2 0  
Fi g ure  1: 
St u d y Sc he m a  
 
I n  t his  st u d y,  patie nts will  be  f oll o we d  f or  s ur vi val  f or  u p  t o  1 8  m o nt hs  after  t he  last  patie nt 
e nr olle d. T he d etaile d st u d y sc h e d ule is s h o w n i n T a ble 1.  
 
 
 
O R R = O bjecti ve res p o nse rate; P F S = Pr o gressi o n -free s ur vi val; D C R = Disease 
c o ntr ol rate; D O R = D urati o n of res p o nse; O S = O verall s ur vi val ; P R Os = 
Patie nt - Re p orte d O utc o mes; P K = P har mac o ki netics.  
A p pr o xi m atel y 1 0 0 tre ate d p atie nts  
•
Prescree ni n g b y l ocal or S p o ns or- desi g nate d ce ntral la b orat or y f or F G F R 2  ge ne 
f usi o n or ot her F G F R 2 rearra n ge me nts i n patie nts wit h hist ol o gicall y or 
c yt ol o gicall y c o nfir me d, l ocall y a d va nce d, metastatic, u nresecta ble i C C A.  
•
At least o ne pri or s yste mic ge m cita bi ne a n d plati n u m-base d c he m ot hera p y.  
Patie nts wit h pri or a dj u va nt ge mcita bi ne -plati n u m c he m ot hera p y are eli gi ble if 
t he patie nt ha d rec urre nce wit hi n 6 m o nt hs of t he last d ose of t he re gi me n. Pri or 
F G F R directe d t hera p y is n ot per mitte d.  
•
D oc u me ntati o n of ra di ol o gic disease pr o gressi o n f oll o wi n g t he m ost rece nt 
pri or t hera p y. 
•
Meas ura ble disease as defi ne d b y R E CI S T g ui deli nes ( versi o n 1. 1, 2 0 0 9). 
T A S - 1 2 0 at 2 0 m g o nce dail y ( Q D) f or 
2 1 da ys ( 2 1- da y c ycles) c o nti n u o usl y  
C o nti n ue u ntil disease pr o gr essi o n, 
u nacce pta ble t o xicit y, wit h dra wal of 
c o nse nt or deat h 
Pri mar y E n d p oi nt :  O R R  
Sec o n dar y E n d p oi nts :  D O R, P F S, D C R, 
O S, P R Os a n d safet y 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020  
Table 1: 
Study Schedule for Phase 2 
NOTE: Evaluations on D1 of a cycle should be performed within 24 hours prior to dosing, unless otherwise noted.  Procedures already 
performed during the screening period within 72 hours prior to dosing do not need to be repeated on C1D1. 
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). 
 
 
 
 
 
Pre-
Screening 
Screening 
Period 
(Within 
28 Days 
Prior to 
First 
Dose) 
Treatment Period (1 cycle = 21 days) 
Safety  
Follow-up 
Survival Follow-
up Period 
Notes 
Cycle 1 
Cycles 
≥2 
End of Tx 
 (+0-7 days) 
30 (±3) days 
After 
Last 
Dose
 
Day 
Day 
1  
4  
(±1d) 
8 
(±3d) 
15 
(±3d) 
1 (±3d) 
Written informed consent 
(X) 
X 
 
 
 
 
 
 
 
 
Pre-screening ICF if required for 
determination of eligibility. 
Tumor tissue testing of FGFR2 
gene fusions / rearrangements 
Tumor tissue may be tested by central laboratory during pre-screening.  If previously tested by central laboratory, tumor tissue should be 
provided if available.  In cases where local laboratory testing is used to determine eligibility, tissue must be submitted to central laboratory for 
confirmation during the study. 
Review eligibility criteria 
 
X 
X 
 
 
 
 
 
 
 
 
Demographics/medical history 
 
X 
 
 
 
 
 
 
 
 
 
Review of pre-existing signs 
and symptoms 
 
X 
X 
 
 
 
 
 
 
 
 
Physical examination 
 
X 
X 
 
 
 
X 
X 
X 
 
Within 24 hours prior to dosing on D1 
of each cycle. 
Vital signs 
 
X 
X 
 
 
 
X 
X 
X 
 
Heart rate, blood pressure, body 
temperature, and respiration rate. 
Height and Weight 
 
X 
X 
 
 
 
X 
X 
X 
 
Height at screening only. 
Ophthalmological examination 
 
X 
 
 
 
 
(X) 
X 
X 
 
At screening and 4-6 weeks after first 
dose; additional on-study evaluation as 
needed due to local requirements, 
physician judgment, and/or symptoms 
or signs of mineral deposits. 
Neurological examination 
 
X 
(X) 
 
 
 
(X) 
X 
X 
 
As clinically indicated after screening, 
using same methods used at screening.   
ECOG performance status 
 
X 
X 
 
 
 
X 
X 
X 
 
Within 24 hours prior to dosing on D1 
of each cycle. 
 
14 


Tai h o O nc ol o g y, I nc. 
 
Statistical A nal ysis Pla n ( P hase 2) – Pr ot oc ol T P U - T A S 1 2 0- 1 0 1 
1 5 Oct o ber 2 0 2 0  
 
 
 
 
 
Pre -
Scree ni n g  
Scree ni n g 
Peri o d  
( Wit hi n 
2 8 D a ys 
Pri or t o 
First 
D ose)  
Tre at me nt Peri o d ( 1 c y cle = 2 1 d a ys)  
S afet y  
F oll o w -u p  
S ur vi v al  F oll o w -
u p Peri o d  
N otes  
C y cle 1  
C y cles 
≥2  
E n d  of  T x  
 ( + 0-7 d a ys)  
3 0 ( ± 3)  d a ys 
After  
L ast 
D ose  
 
D a y  
D a y  
1  
4  
( ± 1 d) 
8  
( ± 3 d) 
1 5  
( ± 3 d) 
1 ( ± 3 d) 
1 2 -Lea d Electr o car di o gra m  
 
X 
X 
 
 
 
X 
X 
X 
 
At scre e ni n g a n d 2 h o urs ( ± 1 5 mi n utes) 
after d osi n g o n D 1 of eac h c ycle.  
He mat ol o g y a n d c o a g ulati o n  
 
X 
X 
 
X 
X 
X 
X 
X 
 
Wit hi n 2 4 h o urs pri or t o treat me nt o n 
D 1  of  eac h  c ycle,  a n y  ti me  o n  C 1 D 8 
a n d C 1 D 1 5, a n d as cli nicall y i n dicate d.  
C he mistr y ( Ser u m or plas ma)  
 
X 
X 
( X) 
X 
X 
X 
X 
X 
 
Wit hi n 2 4 h o urs pri or t o treat me nt o n 
D 1  of  eac h  c ycle,  a n y  ti me  o n  C 1 D 8 
a n d C 1 D 1 5, a n d as cli nicall y i n dicate d.  
A d diti o nal  c ollecti o n  f or  p h os p h or us 
o nl y at C 1 D 4.   
Uri nal ysis ( Uri n e di pstic k)  
 
X  
X  
 
 
 
X  
X  
X  
 
 
Pre g na nc y test  
 
X 
X 
 
 
 
X 
X 
X 
 
Ser u m  pre g na nc y  test  re q uire d  f or 
W O C B P  at  scree ni n g  a n d  e n d  of 
treat me nt;  ser u m  or  uri ne  pre g na nc y 
test re q uire d at all ot her ti me p oi nts. 
Bl o o d P K Sa m pli n g ( Re q uire d)  
 
 
 
 
 
 
X 
 
 
 
Bl o o d sa m ples ( 1 m L) c ollecte d C 2 D 1 
pre- d ose  a n d  at  1 h  a n d  3 h  ( ± 3 0  mi n) 
p ost -d ose.    
A d diti o nal  
sa m ples 
c ollecte d pre-d ose o n C 3 D 1 a n d C 4 D 1.  
ct D N A bl o o d sa m ples  
 
X 
 
 
 
 
 
( X) 
 
 
Mi ni m u m  of  2 0  m L  w h ole  bl o o d  at 
scree ni n g  ( ma n dat or y)  a n d  E O T 
( o pti o nal). 
Pri or  
&  
c o n c o mita nt 
me dicati o ns, A E assess me nts  
X 
X 
 
X 
X 
 
C ollect  fr o m  t he  ti me  mai n  i nf or me d 
c o nse nt is si g ne d t hr o u g h 3 0 da ys after 
a d mi nistrati o n  of  t he  last  d ose  of 
T A S -1 2 0  or  u ntil  t he  start  of  ne w 
a ntica ncer  t hera p y,  
w hic he ver  is 
earlier.  A Es directl y ass ociate d wit h a 
pre- scree ni n g  pr oce d ure  s h o ul d  be 
re p orte d  as  descri be d  i n Pr ot oc ol 
Secti o n 1 2. 1  
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020  
 
 
 
 
 
Pre-
Screening 
Screening 
Period 
(Within 
28 Days 
Prior to 
First 
Dose) 
Treatment Period (1 cycle = 21 days) 
Safety  
Follow-up 
Survival Follow-
up Period 
Notes 
Cycle 1 
Cycles 
≥2 
End of Tx 
 (+0-7 days) 
30 (±3) days 
After 
Last 
Dose
 
Day 
Day 
1  
4  
(±1d) 
8 
(±3d) 
15 
(±3d) 
1 (±3d) 
PRO (EQ-5D and EORTC 
QLQ-C30) 
 
X 
 
 
 
 
X 
X 
 
 
Evaluated at screening and as close as 
possible to the tumor assessment 
schedule: at the end of every 2 cycles 
(up to +2 weeks) through Cycle 4 and 
every 3 cycles (±7 days) thereafter 
until disease progression or initiation 
of new anticancer therapy (whichever 
is first). 
Tumor assessments / scans 
 
X 
 
 
 
 
X 
X 
 
(X) 
Same 
tumor 
assessments/scans 
obtained at screening at the end of 
every 2 cycles (up to +2 weeks) up to 
Cycle 4. Thereafter tumor assessments 
may be performed every 3 cycles (± 7 
days), or as clinically indicated, until 
radiologic PD or initiation of new 
anticancer therapy (whichever occurs 
first).  
At EOT, tumor assessment must be 
performed if the prior scan was 
performed 
≥9 
weeks 
prior 
to 
discontinuation of treatment if the 
patient discontinued for reasons other 
than radiologic disease progression. 
See also Protocol Section 10.17. 
After EOT, patients who discontinued 
for reasons other than radiologic 
disease progression should continue to 
receive tumor assessments every 3 
cycles (± 7 days), or as clinically 
indicated, until radiologic disease 
progression or initiation of new 
anticancer therapy (whichever occurs 
first). 
 
16 


Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020  
 
 
 
 
 
Pre-
Screening 
Screening 
Period 
(Within 
28 Days 
Prior to 
First 
Dose) 
Treatment Period (1 cycle = 21 days) 
Safety  
Follow-up 
Survival Follow-
up Period 
Notes 
Cycle 1 
Cycles 
≥2 
End of Tx 
 (+0-7 days) 
30 (±3) days 
After 
Last 
Dose
 
Day 
Day 
1  
4  
(±1d) 
8 
(±3d) 
15 
(±3d) 
1 (±3d) 
Survival status 
 
 
 
 
 
 
 
 
 
X 
After discontinuation of treatment, 
survival follow-up should occur every 
3 months (±2 weeks) for up to 18 
months after last patient enrolled in the 
Phase 2 portion of the study. 
TAS-120 Dosing 
 
 
 
 
 
 
 
 
 
 
Patients are required to fast for ≥2 
hours before and 1 hour after each 
administration of TAS-120; patients 
are permitted to drink water.  TAS-120 
should be administered in the morning 
or evening, at the same time (if 
possible) each day.  See protocol 
Section 9.1.1. 
 
17 


Tai h o O nc ol o g y, I nc. 
 
Statistical A nal ysis Pla n ( P hase 2) – Pr ot oc ol T P U - T A S 1 2 0- 1 0 1 
1 5 Oct o ber 2 0 2 0 
 
4. 2.  
Tre at me nt Assi g n me nt a n d Bli n di n g/ U n bli n di n g  
After t he patie nt ’s i nitial eli gi bilit y is esta blis he d a n d i nf or me d c o nse nt has bee n o btai ne d, t he 2 0 
m g Q D of T A S - 1 2 0 (F uti bati ni b ) will be a d mi nistere d orall y i n i C C A patie nts. T he treat me nt of 
T A S -1 2 0 will be c o nti n u e d wit h 2 1 -da y treat me nt c ycle u ntil at least o ne of t he criteria f or st u d y 
disc o nti n uati o n criteria is met.  
T his is a n o pe n-la bel st u d y. Bli n di n g/ u n bi n di n g is n ot a p pli e d. 
4. 3.  
Deter mi n ati o n of S a m ple Size  
A p pr o xi matel y 1 0 0 i C C A patie nts wit h F G F R 2  ge ne f usi o ns or ot her F G F R 2  rearra n gem e nts will 
be  treate d. 
 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
5. 
STUDY 
PERIODS, 
TREATMENT 
REGIMENS, 
AND 
POPULATIONS FOR ANALYSIS 
5.1. 
Study Periods 
The study periods are defined in Table 3 below. 
Table 3 
Definition of Study Periods for Analysis 
Period 
Definition 
Baseline / Screening 
From the day of ICF signature (up to 28 days before first dose) to the day and time 
of the first dose of study drug. 
On-treatment  
From the date of first dose of study therapy through 30 days after the last dose of 
study therapy.  Unless otherwise specified, the on-treatment period will be the basis 
for the summaries of safety. 
Abbreviations: ICF=informed consent form. 
5.2. 
Treatment Regimens 
TAS-120 will be administered continuously once daily on a 21-day treatment cycle until at least 1 
of the criteria for study discontinuation is met. TAS-120 will be administered as outlined in Study 
Drug Administration (Protocol amendment 9, Section 9.1.1) and Dose Reduction/Modification 
Procedures (Protocol amendment 9, Section 9.1.3). There are no breaks in dosing between cycles.  
5.3. 
Populations for Analysis 
• Safety Population: 
All patients who received at least 1 dose of TAS-120. This 
population will be the primary population for safety evaluation  
• Efficacy Population: 
All Intra-hepatic cholangiocarcinoma (iCCA) patients who 
received at least 1 dose of TAS-120 with FGFR2 gene fusions or other FGFR2 
rearrangements 
• PRO Population:   All patients who received TAS-120 treatment and had EQ-5D or 
EORTC QLQ-C30 assessment at baseline and at least one subsequent post-baseline 
assessment 
• Per-protocol Patients (Per-Protocol Population):  All treated subjects who have no 
relevant protocol deviations. For patients who have a relevant deviation during the 
study, data collected before the point of deviation can be included in the analysis 
preformed for this population.  
5.4. 
Timing of Analysis 
The final analysis for the primary objective will be performed when majority of patients 
responding to futibatinib had at least 6 months of follow-up from onset of response.  
 
19 
 
 
  
 


Tai h o O nc ol o g y, I nc. 
 
Statistical A nal ysis Pla n ( P hase 2) – Pr ot oc ol T P U - T A S 1 2 0- 1 0 1 
1 5 Oct o ber 2 0 2 0 
 
6.  
S T A TI S TI C A L A N A L Y SI S  
6. 1.  
Ge ner al Met h o ds  
All rele va nt d ata will be prese nte d i n patie nt  le v el data listi n gs.  
All  cate g orical  ( bi nar y  a n d  or di nal)  data  will  be  s u m marize d  usi n g  fre q ue nc y  c o u nts  a n d 
perce nt a ges of patie nts. Perce nta ge will be calc ul ate d usi n g t he c orres p o n di n g treat me nt gr o u p i n 
t he  st u d y  p o p ulati o n  as  t he  de n o mi nat or.  T he  c o nti n u o us  varia bles  will  be  s u m marize d  usi n g 
n u m ber of n o n -missi n g  o bser vati o n ( n), mea n, sta n dar d de vi ati o n ( S D), me dia n,  mi ni m u m a n d 
ma xi m u m u nles s ot her wise s pecifie d. T he n u m ber of e ve nts a n d ce ns ori n gs will be re p orte d f or 
ti me-t o-e ve nt a n al ysis. All esti mati o ns will i ncl u de a p oi nt esti mate a n d t he c orres p o n di n g 9 5 % 
c o nfi de nce i nter val. 
 
T he rec o m me n d e d  p hase 2 d ose ( R P 2 D) is  2 0 m g dail y ( Q D). T h e treat me nt d ose le vel is  2 0 m g 
d uri n g t he re g ular treat m e nt i n P hase 2 of t he st u d y.  
A f or mal i nteri m a n al ysis, as w ell as i nteri m a nal ysis f or safet y will be perf or me d i n t his P hase 2 
part of t he st u d y ( Secti o n 6. 8 ).  
F or c o nc o mita nt me dicati o ns /t hera p y a n d a d vers e e ve nts, t he c ycl es are det er mi ne d base d o n t heir 
start/ o nset  dates.  F or  ot her  c ollect e d  data,  t he  c ycles  are  deter mi ne d  b ase d  o n  t heir  visit  dates. 
T hese  dat a i ncl u de La b  test,  P h ysical  e x a m,  Vital  si g ns,  H ei g ht  a n d  w ei g ht,  O p ht hal m ol o gical  
e x a m,  Ne ur ol o gical  e x a m,  E C O G,  E C G,  Pre g n a nc y  test,  P K,  ct D N A, 
  P R O  data, 
Sc he d ule d t u m or assess me nt. 
 
W he n t here are m ulti ple la b orat or y rec or ds f or a s c he d ule d visit, t he o ne cl osest t o t he tar get date 
(relati ve t o t he Da y 1 i n t hat c ycle) will be use d f or a nal ysis. If t h ere are t w o or m ore rec or ds wit h 
t he sa me ti me peri o d t o t he tar get dat e, t he later one will be use d f or a nal ysis.  
Ti me t o e ve nt distri b uti o n (e. g. pr o gressi o n free s ur vi val, o verall  s ur vi val, ti me t o res p o nse, a n d 
d urati o n  of  res p o nse)  will  be  esti mate d  usi n g  Ka pla n  Meier  tec h ni q ues.  W he n  a p pr o priate,  t he  
me dia n al o n g wit h t he c orres p o n di n g l o g-l o g tra nsf or me d 9 5 % CI will be esti mate d. Rates at fi x e d 
ti me p oi nts will be deri ve d fr o m t he Ka pla n Meier esti mate a n d c orres p o n di n g c o nfi de n ce i nter val 
will be deri ve d base d o n Gree n w o o d f or m ula  f or v aria nce deri vati o n a n d o n l o g-l o g tra nsf or mati o n 
a p plie d  o n  t he  s ur vi v or  f u ncti o n  S(t) . C o nfi de nce  i nter vals  f or  bi n o mial  pr o p orti o ns,  O R R  a n d 
D C R,  will be deri ve d usi n g t he Cl o p per-Pears o n  met h o d. 
 
All t he a n al ys es of efficac y, saf et y, a n d p har mac o d y na mics data f or t his st u d y will be p erf or me d 
usi n g S A S ® statistical s oft ware p ac k a ge, V ersi o n 9. 3 or a later v ersi o n.  
6. 2.  
St u d y C o n d uct  
6. 2. 1.  
Accr u al  
T he  accr ual will be s u m marize d o n t he e nr olle d  p o p ulati o n se paratel y wit h n u m ber of patie nt s 
accr u e d b y c o u ntr y a n d i n vesti gati o nal site. 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
A patient level listing of accrual will also be produced. 
6.2.2. 
Protocol Deviations 
Important protocol deviation (ICH E3 Q&A (R1)) is defined as a subset of protocol deviations that 
may significantly impact the completeness, accuracy, and/or reliability of the study data or that 
may significantly affect the subject’s rights, safety or well-being. These include: Important ICF 
issues, inclusion/exclusion criteria not met, withdrawal criteria not followed; wrong treatment, 
incorrect dose/overdose based on protocol definitions, important deviations based on protocol 
design, and other important GCP deviations.  
Important protocol deviations will be summarized and listed in the Clinical Study Report (CSR).  
Relevant protocol deviations are a subset of important protocol deviations that may impact study 
endpoints. Relevant protocol deviation in phase 2 of this study includes patients who do not have 
evaluable post-baseline tumor assessment.  
6.3. 
Study Population 
6.3.1. 
Patient Disposition 
The number of patients in each study population will be summarized in a table with 5 major 
analysis sets, safety population, efficacy population, per-protocol population, PK population, and 
PRO population. Patient disposition table will include number of patients treated at data cutoff, 
number of discontinued patients along with the reason for exclusion from the population.  In 
addition, patients’ status with regard to study treatment and follow-up will also be summarized, 
along with the reasons for study discontinuations. 
6.3.2. 
Demographic and Other Baseline Characteristics 
The following baseline characteristics will be summarized. Listings will also be provided: 
• Age (descriptive statistics) 
• Age category (<65, >=65) 
• Gender (male, female) 
• Race groups (Caucasian/white, Black, Asian/Oriental, American Indian or Alaska Native, 
Native Hawaiian or Other Pacific Islander, Other) 
• Regions (North America, Europe, Asia Pacific(excluding Japan), Japan) 
• Ethnicity (Hispanic/latino, Not Hispanic/Latino) 
• ECOG Performance Status (1, 0) 
• Baseline Weight (kg) 
• Baseline Height (cm) 
• Baseline FGFR rearrangements status by local lab (commercial test provided to clinician 
as standard of care based on tumor tissue) and/or central lab (clinical trial assay performed 
on tumor tissue) 
• Prior surgical resection of primary tumor (Yes/No) 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
• Prior (neo) adjuvant treatment (Yes, No) 
FGFR2 aberration types will be summarized. A patient level listing will also be provided. 
Pre-study anti-cancer surgery and prior radiation therapy will be summarized. For prior-radiation 
therapy, the number and percentage of patients with palliative and therapeutic radiation therapies 
will be presented in a summary table. 
All prior systemic anticancer therapies (adjuvant therapies, neoadjuvant therapies, therapies for 
advanced/metastatic disease, and maintenance therapies) will be summarized. The number of 
patients with 1, 2, and >=3 prior regimens will be summarized for all systemic anticancer therapies 
and for advanced/metastatic disease only.    
All collected information for cancer diagnosis, pre-study surgery, prior-radiation therapy, and prior 
systemic anti-cancer therapy will be summarized and listed. 
6.3.3. 
Medical History 
Medical history will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA 22.0).  Medical history will be listed by patient number, start date and end date. The 
treatment start date and end date versus the first dose date maybe listed. 
6.3.4. 
Prior/Concomitant Therapy and Therapies 
Prior or concomitant medications and therapies will be collected from the time of informed consent 
through 30 days after administration of last dose of study medication.  
Medications and therapies which started and stopped prior to the first dose of TAS-120 are 
considered as prior medications. Medications and therapies which started prior to the first dose of 
TAS-120 and continued into the treatment period are considered as prior and concomitant 
medications and therapies.  
Medications or therapies with a start date from first dose of TAS-120 to 30 days after 
administration of the last dose of TAS-120 will be considered as concomitant medications or 
therapies.  
Prior and concomitant medications will be coded according to World Health Organization (WHO) 
Drug Dictionary for Concomitant Medication. The concomitant medications will be summarized 
by ATC level 2 (Therapeutic Main Group) and ATC level 4 (Chemical/Therapeutic Subgroup) 
using the number and percentage of patients. Medications will be sorted in descending order of 
frequency of ATC level 2 and ATC level 4 within ATC level 2 in the total column. A patient will 
be counted only once within each level of summation if the patient has taken a medication more 
than once. 
All prior and concomitant medications and therapies will be listed. 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
6.3.4.1. 
Prior Anticancer Therapy 
Pre-study anti-cancer surgery and prior radiation therapy will be summarized. For pre-study 
surgery, the number and percentage of patients with biopsy, primary tumor removal, metastatic 
tumor removal will be reported. For prior-radiation therapy, the number and percentage of patients 
with palliative and therapeutic radiation therapies will be presented in a summary table. 
All prior systemic anticancer therapies (adjuvant therapies, neoadjuvant therapies, therapies for 
advanced/metastatic disease, and maintenance therapies) will be summarized. The number of 
patients with 1, 2 and >=3 prior regimens will be summarized for all systemic anticancer therapies 
and for advanced/metastatic disease only. The number of patients and percent with best of response 
for prior systemic anticancer therapy will also be summarized.   
All collected information for cancer diagnosis, pre-study surgery, prior-radiation therapy, and prior 
systemic anti-cancer therapy will be summarized and listed. 
6.3.4.2. 
Other Prior/Concomitant Therapy 
Prior/current medication will be classified by anatomic and therapeutic classes. Agents and 
medication will be reported using the generic name. A listing by patient will also be provided. 
In addition, percentage of subjects who received concomitant medication for management of 
hyperphosphatemia will be reported by cohort (percentages of treated subjects by medication class 
and generic term).  
Total duration of medications (excluding overlaps) given for management of hyperphosphatemia 
will be also summarized. 
6.4. 
Efficacy Analyses 
6.4.1. 
Primary Efficacy Analyses 
The primary endpoint, Objective Response Rate (ORR), defined as the proportion of patients who 
achieved best overall response of partial response (PR) or complete response (CR) per RECIST 
1.1 based on Independent Review Committee (IRC) in the Efficacy Population, will be 
summarized by a binomial response rate. ORR will be calculated from the best of overall response 
recorded from the start of treatment until progression disease or start of subsequent new anticancer 
treatment. The overall response can be derived based on target lesion response, non-target response 
as well as the emergence of new lesion for patients with measurable disease at baseline. Table 4 
presents the rules to derive the overall response.  
The best overall response, CR and PR, will be confirmed with at least 4 weeks intervals of two 
consecutive time points. A minimum of 6-week interval between initial of treatment (first dose 
date) and tumor measurement is required for SD. The confirmation rule of the best of overall 
response is shown in Table 5. 
95% confidence interval (binomial proportion confidence interval) for ORR will be constructed 
with Clopper-Pearson 95% CI.  The null hypothesis will be rejected if the 2-sided 95% CI lower 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
bound is greater than 10%. This translates in observing at least 17 responders out of 100 in the 
Efficacy Population. 
The objective response rate will be created by both independent review and investigator review. 
The primary endpoints, ORR, assessed with RECIST 1.1, will be displayed in the efficacy tables 
with both independent and investigator review. 
Table 4. Overall Response Assessment with Target/Non-target Lesion and New Lesions 
Target Lesions 
Non-target Lesions 
New Lesions 
Overall 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 
Table 5. Confirmation Rules for Overall Response of PR and CR 
Earlier Response 
(to be confirmed) 
Later Response 
(confirmation) 
Confirmed Response 
CR 
CR 
CR 
CR 
Not CR or missing 
SD 
PR 
CR or PR 
PR 
PR 
SD or PD or missing 
SD 
PR 
SD and then PR (only one SD in between) PR 
SD 
n/a – no confirmation needed 
SD 
PD 
n/a – no confirmation needed 
PD 
6.4.2. 
Secondary Efficacy Analyses 
The Duration of Response (DOR) is defined as the time between the date of first response and the 
subsequent date of objectively documented progression of disease or death. The CR or PR will be 
derived based on investigators or independent radiologist assessment. The censoring rule is shown 
in Table 6. 
Overall survival (OS) is defined as the time between the first dosing date and the date of death. 
Progression free survival (PFS) is defined as the time from the first dosing date to the date of the 
first documented progression or death due to any cause, whichever occurs first. The censoring rule 
is illustrated in Table 6 and Table 7. 
Duration of response (DOR), PFS, and OS will be analyzed using Kaplan–Meier product-limit 
estimates. Median PFS and OS will be presented with 2-sided 95% CI if estimable. Censoring 
rules (Table 6, Table 7) is based on the Food and Drug Administration Guidance for Industry 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics (2007). The cumulative 
PFS and OS will be plotted over time.  
The Disease Control Rate (DCR) is defined as the proportion of patient with objective evidence of 
CR, PR, or SD, except that there is no requirement for a confirmation of an SD response. DCR 
will be calculated and a 2-sided Clopper–Pearson 95% CI will be constructed. 
Table 6.   Censoring Rules for Progression-Free Survival   
No. Situation 
 
End Date 
 
Outcome 
 
1 
Documented PD between scheduled 
visits a 
Date of the first assessment of the 
series of the tests that determined 
PD  
PFS event  
 
2 
Death during the study in absence of PD 
a 
Date of death  
PFS event  
3 
Patients still on treatment without PD as 
of data cut-off b 
Date of last tumor assessment c 
 
Censored  
 
4 
Treatment discontinuation for other 
than PD or death, and no post baseline 
tumor assessments  
Date of first dose 
 
Censored  
 
5 
Treatment discontinuation for other 
than PD or death with post baseline 
tumor assessments  
Date of last tumor assessment  
 
Censored  
 
6 
New anticancer treatment started before 
PD or death  
Date of last tumor assessment c  
before start of new treatment  
Censored  
 
7 
Death or PD after two or more missed 
tumor assessments d 
Date of the last tumor assessment c 
before missed assessments  
Censored 
 
8 
No baseline or unreadable baseline 
assessment but readable post baseline 
assessments  
Date of first dose  
 
Censored  
 
a. 
If documented PD and/or death occurs after the last dose, it is counted as a PFS event as long as the PD and/or the death 
occurs within 21 days since the date of the last dose of study drug and provided that it does not violate other censoring 
rules (e.g. start of new anticancer therapy before the PD or death). Otherwise the patient will be censored on the date of 
last tumor assessment before the date of last dose date + 21 days.  
b. 
For PFS analysis, the date of last tumor assessment refers to the date of last adequate tumor assessment of CR, PR, SD, 
or PD.  
c. 
This refers to patients who were still receiving study treatment at time of data cutoff.  
d. 
Two or more missed tumor assessments is defined as having either one of the following two durations being longer than 
2 cycles for the first 6 months of treatment, or thereafter 3:  
               - Duration between two consecutive tumor assessments  
               - Duration between the last tumor assessment and death or PD.  
 
 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
 
Table 7. 
Censoring Rules for Overall Survival (OS). 
Situation 
End Date 
Outcome 
Death before cut-off 
Date of death  
Death  
Death after data cut-off  
Date of data cut-off  
Censored event  
Patient still alive at data cut-off  
Date of data cut-off  
Censored event  
Patient discontinued treatment due to 
any reason before data cut-off  
Date last known to be 
alive  
Censored event  
 
6.4.2.1. 
Sensitivity Analyses 
The following sensitivity analyses will be performed on the key efficacy endpoints as follows: 
• Primary efficacy endpoint (ORR) based on the Per-protocol Analysis Set using a similar 
analysis method as the primary analysis  
• ORR and PFS based on assessments by the investigator or local radiologist on the Efficacy 
Population 
6.4.3. 
Subgroup Analyses 
To assess consistency of treatment effects in different subsets, IRC assessed ORR (primary 
analysis) will be summarized for the following subgroups.  
• Age group (<65, >=65) 
• Gender (male, female) 
• Race (Caucasian/white, Black, Asian, Other) 
• Baseline ECOG score (0, 1) 
• Prior systemic therapy 1 line, 2 lines, and 3 or more lines for advanced/metastatic disease 
• North America, Europe, Asia Pacific (excluding Japan), Japan,  
• Prior surgical resection of primary tumor (Yes, No) 
• Prior (neo) adjuvant treatment (Yes, No) 
• Baseline FGFR rearrangements status by local lab (commercial test provided to clinician 
as standard of care based on tumor tissue) and/or central lab (clinical trial assay performed 
on tumor tissue) 
• Patients with solid tissue sample and report  
6.5. 
Safety Analyses 
All safety analyses will be performed considering all treated patients.  
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
6.5.1. 
Extent of Exposure 
6.5.1.1. 
Administration of Study Drug 
The number of cycles initiated and completed, extent of exposure (Treatment Duration) relative 
dose intensity in all cycle and total dosage for TAS-120 will be summarized.  
Relative dose intensity (RDI) is defined as the ratio of the amount of drug actually administered 
to the amount planned in the study for TAS-120. The relative dose intensity is calculated in the 
following steps: 
1. Amount of drug actually administered is total number of dose administered  
2. Treatment Duration = last dose date – first dose date +1 
3. Amount of drug planned for the patient =Treatment Duration  
4. Relative Dose Intensity = (Amount of drug actually administered / Amount of drug 
planned) x 100% 
A by-patient listing of dosing of study medication will be also provided. 
 
6.5.1.2. 
Modification of Study Drug 
The number and percentage of patients with at least one dose interruption along with reason for 
the interruptions will be summarized. 
The number and percentage of patient with at least one dose reduction and reason for the dose 
reduction will be summarized. Time to first dose reduction and interruption will be summarized. 
By-patient listings of dose interruptions and dose reductions will be also provided. 
6.5.2. 
Adverse Events 
6.5.2.1. 
Deaths 
All deaths including death due to disease progression occurring in screening, on treatment, 30-day 
safety follow-up, or survival follow-up periods will be summarized. The reasons of death will also 
be summarized. The reasons are categorized in the following terms: 
• Radiological Disease Progression 
• Clinical Disease Progression 
• Toxicity 
• Adverse Event 
• Other 
A by-patient listing of all deaths will be provided for the All Treated Patient population. 
6.5.2.2. 
Serious Adverse Events 
A serious Adverse Event (SAE) is an AE which falls into one or more of the following categories: 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
• Results in death 
• Is life-threatening 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability or incapacity 
• Is a congenital anomaly/birth defect 
• Is any other important medical event 
Serious AEs will be summarized with the following categories: 
• Overall summary of SAEs by worst CTC grade (grade 1, 2, 3, 4, 5, any grade, Grade 3-5) 
presented by SOC/PT. 
• A summary of serious AEs, overall and by system organ class and preferred term. 
Summary of treatment-related serious AE and by-patient listing of SAEs will also be provided. 
6.5.2.3. 
Adverse Events Leading to Discontinuation of Study Drug 
AEs leading to discontinuation will be summarized by treatment group: 
• Overall summary of AEs leading to discontinuation by worst CTC Grade (grade 1, 2, 3, 4, 
5, any grade, Grade 3-5) presented by SOC/PT 
• Overall summary of treatment-related AEs leading to discontinuation by worst CTC grade 
(Grade 1, 2, 3, 4, 5, any grade, Grade 3-5) presented by SOC/PT 
A by-patient listing of AEs leading to discontinuation will also be provided. 
6.5.2.4. 
Adverse Events Leading to Dose Modification 
AEs leading to dose modification (including dose interruption or reduction) will be summarized 
by treatment group: 
• Overall summary of AEs leading to modification by worst CTC Grade (grade 1, 2, 3, 4, 5, 
any grade, Grade 3-5) presented by SOC/PT 
• Overall summary of treatment-related AEs leading to discontinuation by worst CTC grade 
(Grade 1, 2, 3, 4, 5, any grade, Grade 3-5) presented by SOC/PT 
A by-patient listing of AEs leading to modification will also be provided. 
6.5.2.5. 
Adverse Events 
An adverse event (AE) is any untoward medical condition that occurs in a patient while 
participating in this clinical study. Adverse events will be coded according to the Medical 
Dictionary for Regulatory Activities (MedDRA 22.0) terminology and the severity of the toxicities 
will be graded according to the NCI CTCAE, v4.03, where applicable.   
 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
Adverse Events that occur from the initiation of TAS-120 medication administration to 30 days 
after the last dose of study medication, and do not necessarily have a causal relationship to the use 
of the study medication will be summarized.  
Number of patients with AEs will be presented by system organ class in the overall column in 
decreasing order. Within each system organ class, the number of patients with AEs will be 
displayed by preferred term (PT) in descending order.  
The following adverse event summary tables will be generated: 
1) An overall summary with the number and percentage of patients reporting AEs, serious 
AEs, grade 3 or higher AEs, treatment-related AEs, AEs leading to study treatment (TAS-
120) discontinuation and AEs with outcome of deaths.  
In the summary, a patient is counted once at the system organ class and once at each 
preferred term within the system organ class. Additional summary by system organ class, 
preferred term and grade (including Total and >= grade 3 categories) will also be generated. 
2) Study-treatment-related AEs overall and by system organ class and preferred term. 
Additional summary by system organ class, preferred term and grade (including any grade 
and >= grade 3 categories) will also be generated. 
All those AEs with relationship to TAS-120 marked as “Related” or missing will be 
reported in the table.  
3) AEs by highest grade (worse severity) overall and by system organ class and preferred 
term.  
In the summary, a patient is counted once at the highest grade for which the event occurred 
in the system organ class and the highest grade for each unique preferred term within that 
system organ class. Therefore, patients may only contribute once to each preferred term 
and once to each system organ class. The missing severity grade will be reported in a 
separate category. 
4) Grade 3 or higher AEs, overall and by system organ class and preferred term 
5) Study-treatment related AEs by grade (severity) , overall and by system organ class and 
preferred term 
6) AEs leading to study treatment termination, overall and by system organ class and 
preferred term. Additional summary by system organ class, preferred term and grade 
(including Total and >= grade 3 categories) will also be generated. 
7) AEs with outcome of deaths, overall and by system organ class and preferred term  
The time to onset of some special AEs of interest in the study may be summarized if appropriate.   
 
Severity of hyperphosphatemia will be graded based on serum phosphate levels as illustrated in 
Table 8 using identical derivation criteria as specified in the protocol (Protocol section 8.1.3.1.1,).   
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
 
In addition, hyperphosphatemia toxicities grading based on CTCAE v5.0 will also be provided   
using the derivation criteria presented in Table 9. 
 
Table 8. Hyperphosphatemia Toxicity Grading based on serum phosphate levels as specified 
in Protocol * 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Serum  
Phosphorus 
Result 
(mg/dL and mmol/L) 
ULN < P < 5.5 (mg/dL) 
 
ULN < P < 1.78 (mmol/L) 
5.5 ≤ P ≤ 7.0 (mg/dL) 
 
1.78 ≤ P ≤ 2.26 mmol/L) 
7.0 < P ≤ 10.0 (mg/dL) 
 
2.26< P ≤ 3.23 (mmol/L) 
P > 10.0 (mg/dL) 
 
P > 3.23 (mmol/L) 
* Section 8.1.3.1.1, protocol amendment 9  
 
 
Table 9. Hyperphosphatemia Toxicity Grading per CTCAE v5.0 and derivation criteria  
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
CTCAE 
v5.0 
criteria 
Laboratory 
finding only and
intervention 
no
indicated  
Noninvasive 
intervention 
indicated  
Severe 
or 
medically
significant 
but 
no
immediately 
life
threatening; hospitalization
or prolongation of existing
hospitalization indicated  
Life-threatening 
consequences; 
urgent 
intervention 
indicated 
(e.g., dialysis)  
Death  
Derivation 
criteria 
Serum phosphate
> ULN 
Serum phosphate
> ULN 
AND 
concomitant 
therapy 
with
phosphate binder 
Serum phosphate > ULN 
AND 
Concomitant therapy with
phosphate binder 
AND 
SAE 
o
hyperphosphatemia/ 
related toxicity* 
Serum phosphate > ULN 
AND 
Concomitant therapy with
phosphate binder 
AND 
SAE 
o
hyperphosphatemia/ 
related 
toxicity 
with
immediately 
life
threatening 
consequences* 
Death 
due 
to
hyperphosphatemia 
or related toxicity* 
* as assessed by the sponsor  
 
6.5.2.6. 
Adverse Events of Special Interest 
Incidence: 
Adverse event of special interest (AESI, for definition see Section 7.3), including 
hyperphosphatemia, will be summarized for each category/subcategory: 
• Overall summary of AESI by worst CTC grade presented by category or subcategory / PT 
A by-patient listing of AESI will also be provided. 
Time to Onset: 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
Time-to-onset of selected AESI, including hyperphosphatemia, will be graphically displayed for 
each category/subcategory of AESI using the Kaplan-Meier technique: 
• Time to AESI  
• Time to AESI of Grade ≥3  
Summary statistics for time to onset on the patients who had AESI will also be provided.  
 
Time to Resolution: 
Time-to-resolution of selected AESI, including hyperphosphatemia, will be summarized 
separately for each category / subcategory: 
• Time to resolution of AESI 
• Time to resolution of AESI of Grade ≥3  
Time-to-resolution analyses are restricted to treated patients who experienced the specific events.  
The following summary statistics will be reported: percentage of subjects who experienced the 
specific events, percentage of subjects with resolution of the longest AESI, median time-to 
resolution and to ≤ Grade 2 along with 95% CI (derived from Kaplan-Meier estimation, if 
estimable) and ranges. 
6.5.2.7. 
Multiple Adverse Events  
The following summary tables will be provided: 
• Total number and rate (exposure adjusted) of occurrences for all AEs.  
• For AESI: number of subjects experiencing an AESI once or multiple times  
The exposure adjusted incidence rate per X patient time is calculated as X×Y× (total number of 
unique AEs)/(total exposure time), where: 
 X = user-specified time factor, X= 1000 or 100   
 Y = 365.25 for years or Y = 30.4375 for months 
Listing displaying the unique instances of all AEs (that is, after duplicates have been eliminated 
and overlapping and contiguous occurrences of the same event (same PT) have been collapsed) 
will be provided. 
 
6.5.3. 
Clinical Laboratory Evaluations 
Clinical laboratory results will be summarized using SI units. Laboratory measurements will be 
summarized for all protocol scheduled time points for all patients in the safety population. 
Descriptive (n, mean, STD, median, min and max) statistics will be presented for all clinical 
 
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Tai h o O nc ol o g y, I nc. 
 
Statistical A nal ysis Pla n ( P hase 2) – Pr ot oc ol T P U - T A S 1 2 0- 1 0 1 
1 5 Oct o ber 2 0 2 0 
 
c he mistr y,  h e mat ol o g y  a n d  c oa g ulati o n  la b orat or y  para meters  at  eac h  sc he d ule d  visit.  C ha n ge 
fr o m baseli ne at eac h s c h e d ule d p ost-baseli ne visit will als o be prese nte d.  
Patie nt c o u nts a n d perc e nta ges of patie nt f or eac h cate g or y of eac h uri nal ysis para m eters will be 
s u m marize d at eac h sc h e d ule d visit. 
S hift ta bles will be prese nte d f or eac h la b orat or y para meter t o dis pla y t he s hift fr o m baseli ne t o 
t he ma xi m u m p ost-baseli ne C T C A E gra de ( v 4. 0 3) , w here a p plica ble (see als o S ecti o n 6. 5. 2. 5 ). 
S u m mar y  ta bles  will  be  pr o vi de d  prese nti n g  t h e  c o u nt  a n d  perce nta ge  of  patie nts  f or  eac h 
la b orat or y  test  b y  t he  ma xi m u m  p ost-baseli ne  C T C A E  gra d e  re p ort e d.  All  p ost -baseli ne 
assess me nts (i ncl u di n g u nsc he d ule d v isits) will be use d t o deter mi ne t he ma xi m u m ( w orst) p ost-
baseli ne C T C A E gra de. Ti me t o ma xi m u m Gra de 3/ 4 a n d ti me t o res ol uti o n (ret ur n t o gra de < = 2 
or baseli ne gr a de or b el o w) ma y be s u m marize d as a p pr o priate.  
A baseli ne la b or at or y val ue will be defi ne d as t he last assess me nt perf or me d o n or pri or t o t he date 
a n d ti me of first d ose of st u d y treat me nt. La b orat or y test res ults will be cate g orize d b y C T C A E 
criteria V 4. 0 3. 
Esti mate d creati ni ne cl eara nce ( C Lcr) will be calc ulate d usi n g bas eli ne creati ni ne val ue acc or di n g 
t o t he f oll o wi n g f or m ula. 
 
All cli nical la b orat or y data will be prese nte d i n p atie nt  le vel listi n gs. 
T he la b orat or y tests a m o n g H e mat ol o g y, Ser u m c he mistr y, C oa g ulati o n, a n d Uri nal ysis are liste d 
i n Ta ble 1 0. 
Perce nta ge c ha n ge fr o m baseli n e will be s u m marize d f or 
. S u m mar y f or 
 le vels at 
ti me p oi nts: scree ni n g, at t he e n d of e ver y 2 c ycles u p t o c ycle 4, e ver y 3 c ycl es t hereafter, a n d at 
t he e n d of treat me nt will be prese nt e d. Su bject le v el listi n g will als o be ge n erate d.  
T a ble 1 0.   
L a b or at or y Tests 
Assess me nt  
Test Ite ms  
He mat ol o g y  a n d  
C oa g ulati o n 
Re d  bl o o d  cell  c o u nt,  h e m o gl o bi n,  he m at ocrit,  platelets,  w hite  bl o o d  cell 
c o u nt  wit h  differe ntial,  ne utr o p hils,  l y m p h o c yt es,  m o n oc yt es,  e osi n o p hils,  
bas o p hils,  I nt er nati o nal 
n or malize d  rati o  (I N R),  Acti vate d  partial 
t hr o m b o plasti n ti me ( A P T T) 
Ser u m  
c he mistr y 
A S T,  A L T,  A L P,  t otal  bilir u bi n,  gl uc ose,  creati ni ne  cleara nce,  bl o o d  urea 
nitr o ge n ( B U N) or urea, p h os p h or us, calci u m, c hl ori de, s o di u m, p otassi u m, 
creati ne ki nase ( C K), creati ni ne ki nase M B ( C K - M B), Tr o p o ni n I, Tr o p o ni n 
T 
Uri nal ysis  
Uri ne  pr otei n, gl uc ose 
Ot her  
 
•  
Ne utr o p hils  i n cl u d es b ot h  se g me nte d a n d b a n d  n e utr o p hils  
•  
creati ni n e cleara n ce i n cl u d es calc ulate d ( Ccr) or meas ure d creati ni n e cleara n ce  
 
3 2 
 
 
  
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
 
Additional Analysis 
In addition, further analyses on specific laboratory parameters will be performed: 
Abnormal Hepatic Function Test 
The number of subjects with the following laboratory abnormalities from on-treatment 
evaluations will be summarized by treatment group: 
• ALT or AST > 3 x ULN, > 5 x ULN, > 10 x ULN and > 20 x ULN 
• Total bilirubin > 2 x ULN 
• Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN 
• Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN 
The following scatterplots will be produced for the following hepatic laboratory parameters: 
• Total bilirubin peak vs. AST peak 
• Total bilirubin peak vs. ALT peak 
On-treatment peak total bilirubin and on-treatment peak AST/ALT may or may not happen on 
the same day of liver testing.  
A by-subject listing of these specific abnormalities will be provided. 
 
6.5.3.1.1. Ophthalmological Examination 
Ophthalmological examination is performed at screening (within 28 days prior to study medication 
administration on Day 1 of Cycle 1), 4-6 weeks after starting treatment with TAS-120, End of 
treatment visit. Ophthalmological examination results will be summarized and listed. 
6.5.3.1.2. Neurological Examination 
The neurological examination is obtained at screening within 28 days prior to TAS-120 
administration on Day 1 of cycle 1, other time due to local requirements or physician judgement, 
end of treatment visit, and 30-day safety follow-up visit. The examination results will be 
summarized and listed. 
6.5.4. 
Vital Signs 
Vital sign measurements including systolic blood pressure, diastolic blood pressure, pulse rate, 
respiration rate, and temperature at each scheduled and changes from baseline in vital sign 
measurements will be summarized with descriptive statistics at each scheduled time point.  
Weight at each scheduled time and changes from baseline will be summarized with descriptive 
statistics at each scheduled time point for the safety population. Weight will be displayed in 
kilograms, height, collected only at baseline, will be displayed in centimeters, and temperature will 
be displayed in Celsius. The safety population will be used. 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
All vital signs data will be presented in a listing. 
6.5.5. 
Electrocardiograms 
Descriptive statistics for ECG parameters and changes from baseline will be presented by visit and 
treatment group (and/or dose). 
Shift tables will present changes from baseline in ECG interpretation (categorized as normal; 
abnormal, not clinically significant; and abnormal, clinically significant) to end of treatment (or 
end of phase or by visit).  
In addition, the number (percentage) of patients with at least 1 post-baseline abnormal ECG result 
in QTc Fridericia during the on-treatment period will be summarized.  Clinically abnormal ECG 
results based on QTc Fridericia correction will be categorized as follows: 
Absolute QTcF interval prolongation: 
• QTc interval <= 470 ms 
• QTc interval >470 -  480 ms 
• QTc interval > 480 - 500 ms 
• QTc interval > 500 ms 
Change from baseline in QTcF interval: 
• QTC interval increases from baseline <= 30 ms 
• QTC interval increases from baseline 30 -  60 ms 
• QTC interval increases from baseline >  60 ms 
The number patient who experienced QTc abnormalities during the post baseline, but not presented 
in the baseline measurements will be summarized.  
A subject level listing of ECG will be provided. 
6.5.6. 
Physical Examination 
All physical examination is performed 24 hours prior to TAS-120 administration on day 1 
beginning with cycle 2. The baseline screening measurement of physical examination will be taken 
on screening within 28 days prior to TAS-120 administration on Day 1 of Cycle 1. The physical 
examination will also obtain at the End of Treatment Administration, and 30-day safety follow-up 
visit. 
The physical examination data will be presented in a patient level listing. 
6.5.7. 
ECOG Performance Status 
The ECOG performance status score will be obtained at the following time points: screening, and 
24 hours prior to TAS-120 on day 1 beginning with cycle 2, the End of Treatment Administration, 
and 30-day safety follow-up visit. The ECOG performance status scores and the grades from 0 to 
5 are described in the following table: 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
Table 11. 
Grade Categories of Eastern Cooperative Oncology Group Score 
GRADE ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work 
of a light or sedentary nature, eg, light house work, office work. 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. 
Up and about more than 50% of waking hours. 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours. 
4 
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or chair. 
5 
Dead. 
The change from day 1 in cycle 1 in the ECOG performance status scores will be presented in a 
shift table. Time to Deterioration of ECOG performance status to 2 or greater will be summarized.  
A patient level listing will also be presented. 
6.5.8. 
Pregnancy Test 
For female patients with child bearing potential, pregnancy test result will be listed. 
6.5.9. 
Tumor Tissue Sample Collection 
The archived formalin fix paraffin embedded (FFPE) tumor tissue samples will be collected at any 
time while on the study from patients who signed the ICF if available. A patient level listing will 
be produced to display the FFPE output. 
6.6. 
Patient Reported Outcomes (PRO) 
 
Unless otherwise specified, the primary timepoint for the analysis of PRO endpoints is the last 
analysis visit before data is missing for more than 50% of the PRO population. This ‘censoring’ is 
done since when there is more than 50% missing data, reported PRO scores will be very sensitive 
to missing data assumptions. The primary assessment timepoint for the PRO analysis will be 
determined based on a data review prior to the database lock.  
All EQ-5D and EORTC-QLQ-C30 questionnaires completed at baseline and on-study will be 
assigned to a time-point according to the windowing criteria in Table 12 and included in the 
analysis. In case a patient has two on-study assessments within the same window, the assessment 
closest to the time-point will be used. And, in the case of two assessments at a similar distance to 
the time-point, the latest one will be chosen. In the event where the patient has no assessment at 
all in a specific window, the observation will be treated as missing for that time-point. 
 
 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
 
Table 12. Time Windows for EQ-5D and EORTC-QLQ-C30 Assessment 
Nominal Time-Point 
Time Window 
Screening  
-28 to -1 days 
Cycle 2,  Cycle 4 
Day 1 ± 3 days 
>Cycle 4 
Every 3 cycles on day 1 of the cycle ± 7 days 
End of Treatment 
Within 3 days of the decision to discontinuation 
 
 
The Patient-Reported Outcomes (PRO) will be evaluated as close as possible to the tumor assessment schedules.   
6.6.1. 
EQ-5D 
PRO endpoints relating to the EQ-5D are as follows:  
• Shift from screening in the EQ-5D 5 dimensions 
• Change from screening in the EQ-5D-3L Index 
• Change from screening in the EQ-5D-3L VAS score 
There are 5 dimensions: mobility, self-care, usual activities, pain/discomfort and 
anxiety/depression in EQ-5D questionnaire. Each dimension has 3 levels: no problems, some 
problems, severe problems (EQ-5D-3L). Once the data have been collected and a database created, 
a scoring function can be used to assign a value (i.e., EQ-5D index score: 5 dimensions digits 
combined in a 5-digit number) to self-reported health states from a set of population-based 
preference weights.  
The EQ VAS records the patient’s self-rated health state on a 100-point vertical, visual analogue 
scale (0 = worst imaginable health state; 100 = best imaginable health state). 
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), EQ-5D Index and EQ-VAS will be 
provided. 
6.6.2. 
EORTC QLQ-C30 
Functional scales: 
• Physical functioning: (1 - ((Q1+Q2+Q3+Q4+Q5)/5 -1)/3) * 100 
• Role functioning: (1 - ((Q6+Q7)/2-1)/3) * 100 
• Emotional functioning: (1 - ((Q21+Q22+Q23+Q24)/4-1)/3) * 100 
• Cognitive functioning: (1 - ((Q20+Q25)/2-1)/3) * 100 
• Social functioning: (1 - ((Q26+Q27)/2-1)/3) * 100 
Global health status: 
• Global health status/QoL: ((Q29+Q30)/2-1)/6 * 100 
Symptom scales/items: 
 
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Tai h o O nc ol o g y, I nc. 
 
Statistical A nal ysis Pla n ( P hase 2) – Pr ot oc ol T P U - T A S 1 2 0- 1 0 1 
1 5 Oct o ber 2 0 2 0 
 
•  Fati g ue: (( Q 1 0 + Q 1 2 + Q 1 8)/ 3- 1)/ 3 * 1 0 0 
•  Na usea a n d v o miti n g: (( Q 1 4 + Q 1 5)/ 2- 1)/ 3 * 1 0 0 
•  Pai n: (( Q 9 + Q 1 9)/ 2- 1)/ 3 * 1 0 0 
•  D ys p n ea: (( Q 8 - 1)/ 3 * 1 0 0 
•  I ns o m nia: ( Q 1 1- 1)/ 3 * 1 0 0 
•  A p petite l oss: ( Q 1 3 - 1)/ 3 * 1 0 0 
•  C o nsti pati o n: ( Q 1 6- 1)/ 3 * 1 0 0 
•  Diarr hea: ( Q 1 7 - 1)/ 3 * 1 0 0 
•  Fi na ncial diffic ulties: ( Q 2 8 - 1)/ 3 * 1 0 0 
Missi n g val ues will be i m p ute d f or missi n g ite ms b y “ass u mi n g t hat t he missi n g ite ms ha v e val u es 
e q ual t o t he a vera ge of t h ose ite ms w hic h are prese nt” f or a n y scale i n w hic h at least half t he ite ms 
are c o m plete d. A s cale i n w hic h less t ha n half of t h e ite ms are c o m plete d will be treate d as missi n g. 
A q uesti o n naire will be  c o nsi dere d as recei ve d if at least o ne of t he 1 5 scales is n o n -missi n g (after 
i m p utati o n).All scales a n d si n gle ite ms are s c ore d o n a cate g ori cal scale a n d li nearl y tra nsf or me d 
t o  0-t o-1 0 0  scales  wit h  hi g her  sc or es  f or  a  f u ncti o nal  scale  re prese nti n g  hi g her  le vels  of 
f u ncti o ni n g, hi g her sc or es f or t he gl o bal healt h stat us/ q ualit y of life re prese nti n g hi g her le vels of 
gl o bal healt h stat us/ q ualit y of life, a n d hi g her sc ores f or a s y m pt o m scale re prese nti n g hi g her le vel 
of s y m p t o ms. 
P R O e n d p oi nts relati n g t o t he E O R T C Q L Q - C 3 0 are as f oll o ws:  
•  C ha n ge fr o m scree ni n g i n eac h E O R T C Q L Q -C 3 0 scale  
•  Ti me  t o  first  deteri or ati o n  i n  t he  E O R T C  Q L Q -C 3 0  gl o bal  h ealt h  stat us  a n d  p h ysical 
f u ncti o ni n g sc ores 
•  Pr o p orti o n  of  patie nts  wit h  deteri orati o n  b ase d  o n  t he  E O R T C  Q L Q -C 3 0  gl o b al  healt h 
stat us a n d p h ysical f u ncti o ni n g sc ores 
Baseli ne a n d c h a n ge fr o m baseli ne i n E O R T C Q L Q -C 3 0 gl o b al healt h stat us/ q ualit y of life ( Q o L) 
c o m p osite scale data a n d t he re mai ni n g E O R T C Q L Q -C 3 0 scale dat a will be s u m marize d b y ti me 
p oi nt  usi n g  descri pti ve  statistics  f or  eac h  c o h ort.  I n  a d diti o n,  t he  perce nt a ge  of  patie nts 
de m o nstrati n g a cli nicall y mea ni n gf ul deteri orati o n ( defi ne d as a 1 0 -p oi nt c ha n ge fr o m baseli ne) 
will  be  pres e nte d  f or  eac h  scal e  at  eac h  assess me nt  ti me  p oi nt.  Perce nta ges  will  be  b ase d  o n 
n u m ber patie nts assesse d at eac h assess me nt ti me p oi nt.  
T he  c ha n ges  val ues  fr o m  baseli ne  t o  p ost -baseli ne  a n d  s hift  e val uati o n  fr o m  baseli ne  t o  p ost -
baseli ne will be s u m mari ze d.  
 
Ti me t o deteri or ati o n ( T T D) of P R O s c ores is d efi n e d as t he peri o d bet wee n P R O at scree ni n g a n d 
t he first deteri orati o n (i ncl u di n g deat h) .  Patie nt  w h o d i d n ot ha ve p ost- baseli ne deteri orati o n will 
be ce ns or e d  o n t he last d ate of assess m e nt . 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
6.7.1. 
PK Analysis 
Blood samples of TAS-120 will be collected for patient on Day 1 of Cycle 2 pre-dose, post-dose 
1 hour ±0.5 and 3 hours ±0.5 to assess the plasma exposure at 20 mg QD. In addition, blood 
samples will be collected on Day 1 of Cycle 3 and Day 1 of Cycle 4 pre-dose.  
A summary table and subject level listing for plasma concentration will be provided. 
Concentrations in pre-dose samples will be compared among Cycle 2, Cycle 3, and Cycle 4 by 
analysis of variance (ANOVA) with only patients who had neither dose modification nor dose 
interruption. Any samples that were collected after dosing will not be used in the comparison by 
ANOVA. Any patient who have only one pre-dose sample will be excluded from the comparison. 
6.8. 
Interim Analyses 
For interim review of safety, interim analyses of safety will be performed approximately every 
3 months until the formal interim analysis cut-off. These interim safety review will be performed 
by a Safety Review Committee (SRC). 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. The 
tables, graphs, and listings to support the interim safety analyses will be provided in the safety 
review charter. 
In addition, a formal interim analysis of safety and efficacy 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 both interim and primary efficacy analysis of primary efficacy endpoint. 
To facilitate discussion with health authority, additional ad-hoc analysis may be performed as 
deemed appropriate by the sponsor.  
 
 
 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
7. 
DEFINITIONS AND CONVENTIONS FOR DATA HANDLING 
7.1. Baseline Period 
Baseline evaluations or events are defined as evaluations or events that occur before the date and 
time of first dose during study treatment.  
If the onset time of event or evaluation time or dosing time is missing or not collected, the 
following definitions will be applied: 
• Pre-treatment AEs will be defined as AEs with an onset date prior to but not including the 
day of the first dose during study treatment 
• Baseline evaluations (laboratory tests, vital signs) will be defined as evaluations with a date 
on or prior to the day of first dose during study treatment 
If there are multiple valid assessments, the assessment that is closest to day (and time if collected) 
prior to the first dose of study treatment will be used as the baseline in the analyses. If multiple 
assessments are collected at the same date (and time if collected), the assessment with the latest 
database entry date (and time if collected) will considered as baseline. 
7.2. Post-Baseline Period 
On-treatment AEs will be defined as AEs with an onset date and time on or after the date-time of 
the first dose of study drug (or with an onset date on or after the day of first dose of study treatment 
if time is not collected or is missing). An AE will be counted as on-treatment if the event occurred 
within 30 days of the last dose of study treatment. 
 
On-treatment evaluations (laboratory tests, vital signs) will be defined as evaluations taken after 
the day (and time, if collected and not missing) of first dose of study treatment. An evaluation will 
be counted as on-treatment if it occurred within 30 days of the last dose of study treatment. 
7.3. AESI Definition and Conventions 
The AESI consist of a list of preferred terms grouped by specific category (for example, pulmonary 
events, gastrointestinal events categories) and/or by subcategory (for example, diabetes). These 
categories and subcategories are defined based on MedDRA, and the list that is most current at the 
time of analysis will be used.  In addition, changes may be made to this list with each new version 
of MedDRA. 
7.4. Time-to-Onset Definition 
 
Time-to-onset of AESI (any grade) for a specific category (for example, pulmonary events, 
gastrointestinal events) is defined as the time between the day of the first dose of treatment and 
the onset date of the earliest AESI (of any grade) in this category. 
If the subject did not experience an AESI (of any grade) in the category, time-to-onset will be 
censored at the maximum follow-up time of each subject in their respective treatment group (that 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
is, for subjects without an event, follow-up time is defined from first dosing date up to last dosing 
date +30 days if subjects are off treatment and followed for at least 30 days, otherwise it is defined 
up to the last known alive date). The resulting Kaplan-Meier plot will represent the cumulative 
rate of the AESI (any grade) in the category over time. 
Time-to onset of AESI (Grade 3-5) for a specific category is defined similarly but restricted to 
Grade 3-5 AESI. 
Time-to onset of study treatment-related (Grade 3-5 or any grade) AESI for a specific category is 
defined similarly but restricted to study treatment-related AESI. 
Time-to onset for a specific subcategory is defined similarly but restricted to events in this 
subcategory. 
 
7.5. Time-to-Resolution Definition 
In order to derive the time-to-resolution, overlapping or contiguous AESI within a specific 
category will be collapsed into what will be termed “clustered” AESI.  For example, if a subject 
(without pre-treatment AE) experienced an AE from 01 January to 05 January, another AE (with 
different PT but within same category) from 06 January to 11 January, and the same AE from 10 
January to 12 January, these will be collapsed into one clustered AESI from 01 January to 12 
January. Table 13 summarizes key derivation steps for each type of clustered select AEs. 
Algorithm for collapsing multiple records of adverse event is summarized in Section 7.6.  
Time-to-resolution of AESI (any grade) for a specific category is defined as the longest time from 
onset to complete resolution or improvement to the grade at baseline among all clustered AESI in 
this category experienced by the patient. Events which worsened into Grade 5 events (death) or 
have a resolution date equal to the date of death are considered unresolved. If a clustered AESI is 
considered to be unresolved, the resolution date will be censored to the last known date alive. 
Improvement to the grade at baseline implies that all different AE events in the clustered AESI 
should at least have improved to the corresponding (that is, with same preferred term) baseline 
grade. This measure is defined only for subjects who experienced at least one AESI in the specific 
category. 
The time-to-resolution of AESI (Grade 3-5) for a specific category is defined similarly with an 
onset date corresponding to a Grade 3-5 AESI. 
Time-to-resolution of study treatment-related AESI (any grade or Grade 3-5) is defined similarly 
but restricted to study treatment-related AESI. 
Time-to-resolution for a specific subcategory is defined similarly but restricted to events of this 
subcategory. 
 
 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
 
Table 13. 
Derivation of Clustered AESI 
Type of clustered select AE 
Derivation 
Any grade 
Collapse any on-treatment AESI from the same 
category 
 
Study treatment-related of any grade 
Collapse any on-treatment, study treatment-related 
AESI from the same category 
 
Grade 3-5 
Collapse any on-treatment AESI from the same 
category. 
Resolution will be based on the onset date of the earliest 
Grade 3-5 records (if no Grade 3-5 record, clustered 
AESI is excluded) 
Study treatment-related of Grade 3-5 
Collapse any on-treatment, study treatment-related 
AESI from the same category.  Resolution will be based 
on the onset date of the earliest Grade 3-5 record (if no 
Grade 3-5 record, clustered AESI is excluded) 
 
Abbreviations: AE=adverse event; AESI=adverse event of special interest. 
7.6. Multiple Adverse Events 
The algorithm for collapsing multiple records of select adverse event is using the following 
conventions.  For each patient and specified category, the corresponding adverse event records 
will be collapsed when: 
Multiple adverse event records have the same onset date. 
The onset date of an event record is either the same day or 1 day later than the resolution date of a 
preceding event record (contiguous events). 
The onset date of an event record is after the onset date and prior to or on the resolution date of a 
preceding event record (overlapping events). 
 
7.7. 
Other Data Handling Rules 
Missing data will not be imputed in the patient level listings.  The listings will only present the 
data recorded on the original CRF.  
If an AE has a completely missing onset date, then the AE will be considered a TEAE. A 
medication with a completely missing start date is considered a prior medication. A medication 
with a completely missing stop date is considered a concomitant medication.  
 
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Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
If an adverse event or a medication has a partial missing start or stop date, the following rules will 
be used to determine whether it is an AE or a TEAE, or a prior or concomitant medication.  
 
 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
 
Table 14. Partial Date Imputation Rule for TEAE or Medication 
Partial Missing Start or 
Stop Date 
Derived Start Date 
Imputed Stop Date 
Missing month and day, 
and the year is present 
 
January 1 of that year or first dose 
date if the year is the same as the 
year of first dose date 
December 31 of that 
year 
Missing day, but year and 
month are present 
 
First day of that month or first 
dose date if the year and month are 
the same as the year and month of 
first dose date 
Last day of that month 
Missing month, but year 
and day are present 
Missing month derived as January 
or same as first dose month if the 
year is same as the year of first 
dose.  
Missing month imputed 
as December 
 
The rule above in Table 14 is also used for determining the cycles of adverse events and 
concomitant medications.  
 
The derived date is only used for determining TEAEs, cycle of adverse events and concomitant 
medications.  The collected partial dates will be reported in the listings.    
 
For the medical history, prior surgery, prior radiotherapy, and prior systemic cancer therapies: 
• 
Missing day and month - January 1 will be assigned to the missing fields. 
• 
Missing month only - Treat day as missing and replace both month and day according 
to the above procedure. 
• 
Missing day only - Assign first of the month to the missing day. 
 
Partially missing stop dates for the types of data listed above will be imputed as: 
• 
year is missing, no imputation. Date left missing. 
• 
month is missing and year is prior to year of first dose of study medication- impute 
'December'. 
• 
month is missing and year the same as the year of the first dose of study medication – 
impute same month as in start date of study medication. 
• 
day is missing, impute 'last date of that month'. If results in a date ≥ the date of the first 
dose of study medication impute day as the day prior to the first dose of study 
medication. 
 
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Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
8. 
REFERENCES 
1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000 Jan 7;100:57-70. 
2. Borad, M. J., Gores, G. J., & Roberts, L. R. (2015). Fibroblast growth factor receptor 2 fusions 
as a target for treating cholangiocarcinoma. Current Opinion in Gastroenterology, 31(3), 264–
268. http://doi.org/10.1097/MOG.0000000000000171 
3. 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. 
4. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid 
tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47.  
5. 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. 
 
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Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
9. 
REVISION HISTORY  
Table 15: List of changes from Version 1.0 
Section 
Changes from Version 1.0 
Revision Rationale 
5.4 
Section 5.4 Timing of Analysis is added as 
a new section: 
The final analysis for primary objective will 
be performed when majority of treated 
patients responding to futibatinib had at 
least 6 months of follow-up from onset of 
response.  
The timing for analysis is added per 
FDA’s requirement for a complete 
package including efficacy data for all 
patients enrolled in this study and 
ensure that the majority of patients 
have sufficient follow up (i.e., a 
minimum of 6 months from onset of 
response) for the NDA submission 
 
6.4.2 
‘Liver lesions only vs. lesions in and 
outside of liver’ is removed from subgroup 
analysis 
This information was not collected in 
the EDC per CRF design.  
6.4.2 
The following subgroup analysis is added: 
•  Prior (neo) adjuvant treatment 
(Yes, No) 
• Baseline 
FGFR 
rearrangements 
status by local lab (commercial test 
provided to clinician as standard of 
care based on tumor tissue) and/or 
central lab (clinical trial assay 
performed on tumor tissue) 
• Patients with solid tissue sample 
and report  
(neo) Adjuvant is a relevant subgroup 
of interest  
Biomarker test subgroup analysis are 
added per FDA CDx request 
6.5.2.5 
Add 
additional 
analysis 
of 
Hyperphosphatemia toxicities based on 
CTCAE v5.0 criteria (Table 9) 
To have a comprehensive assessment 
of hyperphosphatemia, analysis based 
on both CTCAE v5.0 criteria and 
protocol specified criteria will be 
performed. 
6.5.3 
Liver toxicity analysis are added.  
The number of subjects with the following 
laboratory abnormalities from on-treatment 
evaluations will be summarized  
Revised 
per 
the 
FDA’s 
recommendation 
to 
include 
liver 
toxicity analysis. 
 
45 
 
 
  
 


Taiho Oncology, Inc. 
 
Statistical Analysis Plan (Phase 2) – Protocol TPU-TAS120-101 
15 October 2020 
 
• ALT or AST > 3 x ULN, > 5 x ULN, > 10 
x ULN and > 20 x ULN 
• Total bilirubin > 2 x ULN 
• Concurrent (within 1 day) ALT or AST > 
3 x ULN and total bilirubin > 2 x ULN 
• Concurrent (within 30 days) ALT or AST 
> 3 x ULN and total bilirubin > 2 x ULN 
The following scatterplots will be produced 
for the following hepatic laboratory 
parameters: 
• Total bilirubin peak vs. AST peak 
• Total bilirubin peak vs. ALT peak 
On-treatment peak total bilirubin and on-
treatment peak AST/ALT may or may not 
happen on the same day of liver testing.  
A by-subject listing of these specific 
abnormalities will be provided. 
6.5.3  
Delete following paragraphs in section 
6.5.3 
“Any laboratory abnormality that has a 
clinical impact on the patient, eg, results in 
delay 
of 
study 
drug 
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 
< 1000/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 CTCAE grade criteria 
(Version 4.03).” 
“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 another anticancer treatment is 
started.” 
Deleted paragraphs are described in 
protocol. They are guidance as what 
should 
have 
been 
reported 
as 
AE/clinical 
follow-up. 
It 
is 
not 
necessary to repeat them in SAP. 
 
46 
 
 
  
 


Tai h o O nc ol o g y, I nc. 
 
Statistical A nal ysis Pla n ( P hase 2) – Pr ot oc ol T P U - T A S 1 2 0- 1 0 1 
1 5 Oct o ber 2 0 2 0 
 
“ F or  all  t he  patie nts,  bl o o d  sa m ples  f or 
meas ure me nt of 
 le vels is c ollecte d 
d uri n g  Scree ni n g  wit hi n  2 8  da ys  pri or  t o 
T A S -1 2 0 a d mi nistrati o n o n Da y 1 of C ycl e 
1.  T hereafter,  s a m ples  will  be  c ollecte d  i n 
c o nj u ncti o n wit h t u m or assess me nts/sca ns, 
i.e., at t he e n d of e ver y 2 c ycles u p t o C ycle 
4,  a n d  e ver y  3  c ycles  t hereafter,  or  as 
cli nicall y i n dicat e d, a n d at t he E O T Visit.”  
Ot her  
E dit orial c ha n ges i ncl u de: 
1.  C ha n ge “ dr u g r elate d” t o “treat me nt 
relate d” t hr o u g h o ut t he d oc u me nt 
2.  c ha n ge  “a nti -ca ncer  t h era p y”  t o 
“s yste mic a nti-ca n cer t h era p y”  
3.  Re m o ve a b br e viati o n a n d refere n ce 
t hat wer e n ot us e d a n y w here i n t his 
S A P  
 
 
 
4 7 
 
 
  
 
C CI