A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring Fibroblast Growth Factor Receptor (FGFR) Amplifications
Phase: PHASE2
Conditions: Metastatic Breast Cancer, FGFR 1 High Amplification, FGFR2 Amplification
Sponsor: Taiho Oncology, Inc.

 
Oﬃcial Title: A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring 
Fibroblast Growth Factor Receptor (FGFR) Ampliﬁcations 
  
NCT ID: NCT04024436 
  
Document Date: Protocol Amendment 1, 07 June 2019 
 

TAS-120
Protocol TAS-120-201, Amendment 1 (Version 2.0)
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CLINICAL STUDY PROTOCOL
A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring 
Fibroblast Growth Factor Receptor (FGFR) Amplifications
TAS-120
Protocol Number: TAS-120-201
Protocol Version Number: 1.0
Issue Date: 18 March 2019
IND Number: 142345
EudraCT Number : 2019-001164-30
Amendment 1 (Version 2.0):  07 June 2019
Sponsor
Taiho Oncology, Inc.
101 Carnegie Center, Suite 101
Princeton, NJ 08540, USA
This clinical study will be conducted in accordance with the International Council for
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, Good 
Clinical Practice guidelines and applicable regulatory requirements.
CONFIDENTIAL
The information contained in this document is the property of Taiho Oncology, Inc. (TOI). This 
document contains strictly confidential information and no part of this document may be 
published or disclosed without the prior written approval of TOI, except by request from 
competent authorities.

TAS-120
Protocol TAS-120-201, Amendment 1 (Version 2.0)
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OVERVIEW OF CHANGES 
The primary purpose of this amendment was to incorporate changes based on comments 
received by the Sponsor from the United States (US) Food and Drug Administration (FDA). 
Substantive changes are described in the table below.  All changes have been incorporated into 
the study synopsis as appropriate; the Table of Contents and list of abbreviations and terms have 
also been updated when necessary.
In addition to these substantive changes, minor administrative alterations were made as 
necessary throughout the protocol, including formatting adjustments and correction of 
typographical errors.  These editorial changes do not affect the rationale or planned conduct of 
the study or analyses, and therefore are not summarized in the table below.
Affected Section(s)
Description of Change(s)
Brief rationale 
Cover Page
Added EudraCT Number to protocol cover.
Administrative change.
Section 1.3
Summary of Study Rationale
Section 2
Objectives and Endpoints
Section 6.1.8
Pharmacokinetic Evaluations
Section 9.2
Population Pharmacokinetic 
Sample Collection and Analysis
Section 10.3
Analysis Populations
Section 10.5.4
Pharmacokinetic Analysis
Protocol amendment 1 added plasma sample 
collection for PopPK analyses; this included the 
addition of a corresponding exploratory
objective, the addition of Section 9.2, describing 
collection and analysis of samples, and additions 
/ amendments to the statistical methods defining 
the PopPK analysis set and discussing analysis 
and summarization of data.
This addition is intended to provide 
additional evidence regarding the
pharmacokinetics of TAS-120.
Section 4.1
Inclusion Criteria
Inclusion Criterion #4 was updated with several 
clarifications related to permitted prior therapies
Clarification of intended practice.
Section 4.1
Inclusion Criteria 
And throughout document.
Increased the required duration of contraception 
to 1 year after last dose of fulvestrant.
This change was made to ensure 
consistency with the approved US
prescribing information for 
fulvestrant.
Section 4.3
Screen Failure
Corrected prior text indicating that patients who 
do not meet entry criteria may be rescreened up 
to 3 times (patients may be rescreened up to 2 
times).
Correction of error.
Section 5.2
Definition of a Dose-Limiting 
Toxicity (Cohort 4 Only)
The definition of a DLT provided in Table 3 was 
modified per regulatory feedback.
All changes made per request by the 
FDA.
Section 5.3.1.1
Dose and Schedule Modifications 
for TAS-120: General 
Considerations
Specified that for Cohort 4, in cases where 
toxicity is not clearly attributable to either study 
drug, TAS-120 will be modified or discontinued 
first.
Clarification of intended practice.
Section 6.1.4
Laboratory Assessments
Removed requirement that corrected value for 
calcium be provided.
Administrative change to reduce 
risk of calculation errors.

TAS-120
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PROTOCOL SYNOPSIS
Name of Sponsor/Company:
Taiho Oncology, Inc.
Name of Investigational Product:
TAS-120
Title of Study:
A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring Fibroblast Growth Factor Receptor (FGFR) 
Amplifications 
Phase of Development: 
Phase 2
Study Rationale:
FGFR gene mutations, particularly amplifications, play an important role in the development of breast cancer; 
FGFR1 and FGFR2 gene amplifications are present in approximately 10% and 2%, respectively, of all invasive 
breast cancers.  TAS-120, an inhibitor of FGFR1-4, has shown promising preclinical activity in the treatment of 
breast cancers and other cancer types; in a Phase 1 clinical study, TAS-120 monotherapy was associated with 
2 durable partial responses (PRs) in patients with treatment-refractory breast cancer. 
Accordingly, this Phase 2 study will include patients with breast cancer harboring FGFR gene amplifications.  
Recent evidence suggests that the addition of an FGFR inhibitor may overcome resistance to hormonal therapy in 
breast cancer (Turner et al. 2010).  Accordingly, patients in this study will receive either single-agent TAS-120 or 
combination treatment comprising TAS-120 and fulvestrant. 
A safety lead-in will be performed for the combination of TAS-120 and fulvestrant to assess any overlapping or 
exacerbated toxicities with adjustment of the dose of TAS-120 if required.
The maximum tolerated dose (MTD) of TAS-120 is 20 mg QD (continuous daily dosing), based on the results of 
the Phase 1 dose escalation portion of Study TAS-120-101.  Accordingly, the starting dose of TAS-120 in this 
Phase 2 study will be 20 mg QD.
Objectives and Endpoints:
Primary
The primary objective of this study is to assess the antitumor activity of TAS-120 as monotherapy or in 
combination with fulvestrant in the treatment of patients with metastatic breast cancer harboring FGFR
amplifications, as measured by: 

Objective response rate (ORR) in patients with centrally confirmed FGFR2 amplification and measurable 
disease (Cohorts 1, 2);

Clinical benefit rate (CBR) in patients with centrally confirmed FGFR2 amplification and nonmeasurable, 
evaluable disease (Cohort 3); and

6-month progression-free survival (PFS) rate in patients with centrally confirmed high level FGFR1
amplification and measurable disease (Cohort 4)
Secondary

To determine the complete response (CR) rate in Cohort 3, the ORR in Cohort 4, the CBR in Cohorts 1, 2, 
and 4, and the 6-month PFS rate in Cohorts 1-3. 

To evaluate the duration of response (DOR) among patients with objective response in any cohort.

To evaluate the PFS and overall survival (OS) in all cohorts.

To investigate the safety of TAS-120 as monotherapy and in combination with fulvestrant.
Exploratory

To investigate the downstream pharmacodynamic effects of treatment with TAS-120.

To explore markers of response and mechanisms of resistance in tumor tissue biopsies and/or blood.

To explore PK of TAS-120 by population pharmacokinetic (PopPK) analysis and exposure-response 
analyses.

TAS-120
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Name of Sponsor/Company:
Taiho Oncology, Inc.
Name of Investigational Product:
TAS-120
Title of Study:
A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring Fibroblast Growth Factor Receptor (FGFR) 
Amplifications 
Study Design: 
This is a Phase 2, open-label, non-randomized, multicenter study designed to evaluate the efficacy and safety of 
TAS-120 and TAS-120 + fulvestrant in adult patients with locally advanced/metastatic breast cancer harboring 
FGFR gene amplifications.  Patients will be enrolled to 1 of 4 treatment cohorts based on diagnosis and FGFR gene 
amplification status (as shown in the figure below), and will receive either single agent TAS-120 in Cohorts 1-3 or 
TAS-120 plus fulvestrant in Cohort 4.
In all cohorts, a treatment cycle is defined as 28 days.  All patients will receive oral (PO) TAS-120 at a dose of 
20 mg QD (continuous daily dosing).  Patients in Cohort 4 will also receive intramuscular (IM) fulvestrant 500 mg 
on Days 1 and 15 of Cycle 1 and Day 1 of every subsequent cycle. Pre/peri-menopausal patients in Cohort 4 are 
required to also have ovarian suppression with goserelin as part of standard of care, having started a gonadotropin-
releasing hormone (GnRH) analogue at least 4 weeks prior to the first dose of fulvestrant.
Treatment will continue until disease progression, unacceptable toxicity, or any other of the criteria for treatment 
discontinuation is met. For patients who discontinue treatment for reasons other than disease progression, tumor 
assessments should be continued until radiologic disease progression is documented or until initiation of subsequent 
new anticancer therapy (whichever occurs first). Patients will be followed for survival every 12 weeks (±2 weeks) 
until survival events (deaths) have been reported for 75% of enrolled patients or the study is terminated early by the 
Sponsor.
Cohorts 1 and 2 will initially enroll a total of approximately 19 response-evaluable patients per cohort. If 
≥4 responses (PR or CR) are observed in a cohort, that cohort will be further expanded to a total of approximately 
55 response-evaluable patients.
Cohort 3 will initially enroll a total of approximately 9 response-evaluable patients. If ≥3 patients experience 
clinical benefit (CR, or stable disease [SD] ≥24 weeks), the cohort will be further expanded to a total of 
approximately 24 response-evaluable patients.
Because the combination of TAS-120 and fulvestrant has not been assessed in patients, Cohort 4 will begin with a 
safety lead-in period.  During the safety lead-in, 3 patients will initially be enrolled and will receive TAS-120
(20 mg QD) and fulvestrant (500 mg) according to the study schedule, with safety follow-up of at least 1 cycle. 

TAS-120
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Name of Sponsor/Company:
Taiho Oncology, Inc.
Name of Investigational Product:
TAS-120
Title of Study:
A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring Fibroblast Growth Factor Receptor (FGFR) 
Amplifications 
Patients will be assessed for dose-limiting toxicities (DLTs) and the recommended dose of TAS-120 for this cohort 
will be determined on the basis of this assessment; a total of 28 patients will ultimately be enrolled and treated at 
the recommended dose. 
Number of Patients: 
Up to approximately 168 patients will be enrolled in this study.
Inclusion/Exclusion Criteria: 
Inclusion:
A patient must meet all of the following inclusion criteria to be eligible for participation in this study.  
1.
Patient provides written informed consent.
2.
Patient is ≥18 years of age (or meets the country’s regulatory definition for legal adult age, whichever is 
greater)
3.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
4.
Histologically or cytologically confirmed recurrent locally advanced or metastatic breast cancer not 
amenable to treatment with curative intent, meeting all of the criteria for 1 of the following cohorts: 
A.
Cohort 1
i.
Hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative
(HER2-) breast cancer harboring an FGFR2 gene amplification. HR+ HER2- breast cancer is 
defined per the local pathology report as estrogen receptor (ER) >1% and/or, progesterone 
receptor (PR) >1%, HER2-negative per the American Society of Clinical Oncology (ASCO) 
and the College of American Pathologists (CAP) guidelines, 2018. 
ii.
Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
iii.
Has received 1-3 prior endocrine-containing therapies and up to 2 prior chemotherapy 
regimens for advanced/metastatic disease
iv.
Has received prior treatment with a CDK4/6 inhibitor or is ineligible for such treatment (per 
Investigator decision)
v.
Has experienced disease progression/recurrence within 1 month following the completion of 
any endocrine therapy for advanced/metastatic breast cancer
B.
Cohort 2
i.
Triple Negative Breast Cancer (TNBC) harboring an FGFR2 gene amplification. TNBC is 
defined as negative for ER, PR and HER2. Negative for ER and PR includes the following: 
local pathology report classifies them as negative, Allred Score of 2 or below or <1% 
staining. HER2-negative per ASCO / CAP guidelines, 2018.
ii.
Measurable disease per RECIST 1.1
iii.
Has received at least 1 prior chemotherapy or chemotherapy/immunotherapy (PD-L1/PD-1 
inhibitors) regimen for advanced/metastatic disease
iv.
Has experienced disease progression/recurrence during or after the most recent prior 
chemotherapy for advanced/metastatic breast cancer
C.
Cohort 3
i.
TNBC or HR+ HER2- breast cancer (defined as above) harboring an FGFR2 gene 
amplification 
ii.
Nonmeasurable, evaluable disease per RECIST 1.1. Patients with bone-only disease must 
have lytic or mixed lytic-blastic lesions
iii.
Other criteria for either HR+ HER2- breast cancer or TNBC should be met as described for 
Cohort 1 and 2, respectively
D.
Cohort 4
i.
HR+ HER2- breast cancer (defined as above) harboring an FGFR1 high-level gene 
amplification as defined in Section 6.1.1.1

TAS-120
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Name of Sponsor/Company:
Taiho Oncology, Inc.
Name of Investigational Product:
TAS-120
Title of Study:
A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring Fibroblast Growth Factor Receptor (FGFR) 
Amplifications 
ii.
Measurable disease per RECIST 1.1
iii.
Has received 1-2 prior endocrine-containing therapies and no more than 1 prior 
chemotherapy regimen for advanced/metastatic disease. Prior treatment with fulvestrant is 
not permitted.
iv.
Has received prior treatment with a CDK4/6 inhibitor or is ineligible for such treatment (per 
Investigator decision)
v.
Pre/peri-menopausal patients must be on goserelin. Patients must have commenced treatment 
with goserelin or an alternative GnRH agonist at least 4 weeks prior to the first dose of 
fulvestrant. If patients have received an alternative GnRH agonist prior to study entry, they 
must switch to goserelin for the duration of the trial.  Postmenopausal is defined as at least 
one of the following criteria: age ≥60 years; age <60 years and cessation of regular menses 
for at least 12 consecutive months with no alternative pathological or physiological cause; 
and serum estradiol and follicle-stimulating hormone level within the laboratory’s reference 
range for postmenopausal females; or documented bilateral oophorectomy.
vi.
Has experienced disease progression/recurrence within 1 month following the completion of 
any endocrine therapy for advanced/metastatic breast cancer.
5.
Archival or (preferably) fresh tumor tissue must be available for central laboratory confirmation of FGFR
amplification.
6.
The patient is able to take medications orally (a feeding tube is not permitted).
7.
The patient has adequate organ function as defined by the following criteria:
a.
AST and ALT ≤3.0×ULN; if liver function abnormalities are due to underlying liver metastases, AST 
and ALT ≤5×ULN.
b.
Total bilirubin ≤1.5×ULN or ≤3×ULN in case of Gilbert’s syndrome
c.
Absolute neutrophil count (ANC) ≥1.0×109/L without hematopoietic growth factor support 
d.
Platelet count ≥75×109/L without transfusion support (that is, excluding measurements obtained 
within 3 days after transfusion of platelets)
e.
Hemoglobin ≥9.0 g/dL without transfusion support (that is, excluding measurements within 7 days 
after transfusion of packed red blood cells or whole blood)
f.
Serum phosphorus ≤ ULN
g.
Creatinine clearance (calculated or measured value): ≥40 mL/min
8.
Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test 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 90 days after the last dose
of TAS-120 and 1 year after last dose of fulvestrant (Cohort 4 only).
9.
The patient is willing and able to comply with scheduled visits and study procedures.
Exclusion:
A patient must not meet any of the following exclusion criteria to be eligible for participation in this study:
10. History and/or current evidence of any of the following disorders:
a.
Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically 
significant in the opinion of the Investigator
b.
Ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, or 
myocardia and lung, considered clinically significant in the opinion of the Investigator
c.
Retinal or corneal disorder confirmed by retinal/corneal examination and considered clinically 
significant in the opinion of the Investigator.
11. Corrected QT interval using Fridericia’s formula (QTcF) >470 msec. Patients with an atrioventricular 
pacemaker or other condition (for example, right bundle branch block) that renders the QT measurement 

TAS-120
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Name of Sponsor/Company:
Taiho Oncology, Inc.
Name of Investigational Product:
TAS-120
Title of Study:
A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring Fibroblast Growth Factor Receptor (FGFR) 
Amplifications 
invalid are an exception and the criterion does not apply.
12. Treatment with any of the following within the specified time frame prior to the first dose of TAS-120:
a.
Major surgery within 4 weeks (the surgical incision should be fully healed)
b.
Radiotherapy for extended field within 4 weeks or limited field radiotherapy within 2 weeks
c.
Any prior systemic therapy regardless of the stop date, but the patient must have recovered to 
eligibility levels from prior toxicity
d.
Any investigational agent received within 30 days or 5 half-lives (whichever is shorter)
13. Prior treatment with an FGFR inhibitor
14. Cohort 4 only: Prior treatment with fulvestrant, or known hypersensitivity to fulvestrant.
15. A serious illness or medical condition(s) including but not limited to the following:
a.
Known acute systemic infection
b.
Myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure within the 
previous 6 months
c.
History or current evidence of serious uncontrolled ventricular arrhythmia
d.
Chronic diarrhea diseases 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 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
16. Brain metastases that are untreated or clinically or radiologically unstable (that is, have been stable for <1 
month).
17. History of another primary malignancy that is currently clinically significant or currently requires active 
intervention
18. Pregnant or lactating female
Pharmacokinetics:
Samples will be collected for PopPK analysis, including estimation of steady-state exposure such as area under the 
plasma-concentration time curve (AUC).  PopPK samples will be collected on Cycle 2, Day 1, within 1 hour prior 
to dosing and at 2 hours (±1 hour) and 5 hours (at least 3 hours apart from sampling at 2 hours) post-dose.  Details 
on the collection will be provided in a separate Laboratory manual.  Detailed analytical procedures will be 
described in the SAP.
Pharmacodynamics:
The pharmacodynamic biomarker population will consist of all patients who received TAS-120 and have evaluable 
pharmacodynamic biomarker data. 
A blood sample will be collected to assess FGF/FGFR aberrations in ctDNA prior to the first TAS-120
administration on Day 1 of Cycle 1, on Day 1 of each alternative uneven cycle (Cycle 3, 5, 7 and ongoing), at time 
of disease progression, and at the end-of-treatment (EOT) visit. 
Archival or fresh tumor biopsy samples will be collected during the screening period to retrospectively confirm 
FGFR gene status at the Sponsor’s designated central laboratories. Optional pre- and post-treatment tumor biopsies 
for pharmacodynamic assessment will be collected from patients who consent at Baseline, at the end of Cycle 1 
(Cycle 1 Day 28 ± 7 days), and at the time of disease progression. These samples are being collected for 
exploratory analysis to evaluate the changes of downstream protein activation and other markers that may be 
associated with response and/or development of resistance to TAS-120 in tumor tissues.
Criteria for Evaluation:
Efficacy
Measurements will be performed throughout study treatment using RECIST guidelines (version 1.1, 2009).  

TAS-120
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Name of Sponsor/Company:
Taiho Oncology, Inc.
Name of Investigational Product:
TAS-120
Title of Study:
A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring Fibroblast Growth Factor Receptor (FGFR) 
Amplifications 
Radiographic tumor assessments (computed tomography [CT] scan with contrast) will be performed at baseline and 
at the end of every 8 weeks/2 cycles (±1 week) or as clinically indicated until disease progression, death, or 
withdrawal of consent, and at the end of therapy. Magnetic Resonance Imaging (MRI) scans may be performed if 
required to assess measurable lesions. The following efficacy endpoints will be evaluated:

ORR: defined as the proportion of patients with a confirmed response of either CR or PR per Investigator 
assessment.

CBR (Cohort 3): defined as the proportion of patients with a confirmed response of CR, or SD lasting at 
least 24 weeks, per Investigator assessment.

CBR (All Other Cohorts): defined as the proportion of patients with a confirmed response of CR or PR, 
or SD lasting at least 24 weeks, per Investigator assessment.

6-month PFS rate: defined as the proportion of patients who are alive and progression-free 6 months after 
the first dose of study therapy.

DOR: defined as the time from first documentation of objective response to the date of death (any cause) 
or disease progression per Investigator assessment.

PFS: defined as the time from the first dose of study therapy to the date of death (any cause) or disease 
progression per Investigator assessment.

OS: defined as the time (in months) from the first dose of study therapy to the date of death (any cause).
Safety
Standard safety monitoring and grading of treatment-emergent adverse events (AEs) will be performed using 
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (Version 5.0).  Other 
safety evaluations will include vital signs, electrocardiogram (ECG), ophthalmology exams, and laboratory testing 
(hematology, chemistry, coagulation). Evaluation of DLTs will be performed for Cohort 4 only.
Statistical Methods:
Approximately 168 patients in total may be enrolled in the study. Sample size considerations for Cohorts 1 and 2
(primary endpoint ORR) are based on a 2-stage Optimal Simon design, comparing a poor response of ≤15% versus 
a promising response of ≥30%, at an approximate 5% 1-sided significance level and 80% power.

In Stage 1 (futility assessment), enrollment will include 19 patients in each cohort and accrual will 
continue to Stage 2, if at least 4 (21%) of 19 patients respond (CR or PR). 

In Stage 2, if the Stage 1 futility boundary is exceeded, an additional 36 patients will be enrolled, for a 
total of at least 55 patients per cohort.  In Cohorts 1 or 2, with a total of 55 patients, if the observed ORR is 
30.9%, the 95% exact confidence interval (CI) is (19.1%, 44.8%).
Sample size considerations for Cohort 3 (primary endpoint CBR) are also based on a 2-stage Optimal Simon 
design. The null hypothesis that the true CBR is 25% will be tested against a 1-sided alternative, which yields a 
type I error rate of 5% and power of 80% when the true CBR rate is 50%. In the first stage, 9 patients will be 
treated. If there are ≤2 patients with clinical benefit (ie, CR or SD ≥24 weeks) in these 9 patients, the cohort will be 
discontinued. Otherwise, 15 additional patients will be treated for a total of 24 patients. The null hypothesis will be 
rejected if ≥11 patients with clinical benefit are observed in 24 patients. 
Sample size considerations for Cohort 4 (primary endpoint 6-month PFS) are based on a proof-of-concept Phase 2 
design, differentiating a null 6-month 25% PFS rate with a target rate of 50%. Approximately 28 patients will be 
treated. It has approximately 80% power to reject the null hypothesis that the true 6-month PFS rate is ≤25%, 
considering a 1-sided alpha (type 1 error rate) of 5%. In addition, 6-12 patients will be enrolled as a safety lead-in. 
The patients in the safety lead-in who are treated at the recommended Phase 2 dose will be included in the main 
cohort of 28 patients. Thus up to 34 patients may be enrolled for this cohort.

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Name of Sponsor/Company:
Taiho Oncology, Inc.
Name of Investigational Product:
TAS-120
Title of Study:
A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring Fibroblast Growth Factor Receptor (FGFR) 
Amplifications 
Interim Analyses:
Per the study design described above, the Sponsor will review the data at the time a cohort has the required number 
of patients to determine if that particular cohort should continue.
Countries:
Patients will be enrolled at study sites in the United States (US) and internationally.
Number of Sites:
This study will be conducted at approximately 75 sites globally.

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Table 1:
Schedule of Events
Written informed consent will be obtained prior to any study evaluations.  Evaluations on Day 1 (D1) of a cycle should be performed 
within 24 hours prior to dosing, unless otherwise noted.  Procedures already performed during the screening period within 96 hours prior 
to dosing do not need to be repeated on Cycle 1 Day 1 (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 = 28 days)
Safety 
Follow-up
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
(±1d)
15
(±1d)
22
(±1d)
1 
(±3d)
Demographics / medical history
X
Includes sex, age, clinical diagnosis, date 
and method of diagnosis, prior cancer 
therapy, and relevant medical history (past 
and concurrent).
Review eligibility criteria
X
X
Eligibility should be confirmed on C1D1 
prior to first dose of study therapy.
Collect tumor tissue
X
Archival or fresh (preferred) tumor tissue 
biopsy samples must be made available 
during the screening period.  
Submit tumor tissue to central 
laboratory
X
Tumor samples must be submitted to a 
designated central laboratory for testing as 
soon as possible after the patient is 
enrolled. Tumor samples may be stored at 
the Sponsor’s designated central 
laboratory for up to 10 years for future 
testing.
Physical examination
X
X
X
X
X
  
Vital signs
X
X
X
X
X
Pulse rate, systolic and diastolic blood 
pressure, body temperature, and 
respiration rate. Any abnormal reading 
should be repeated immediately.
Height and body weight 
X
X
X
X
X
Height at baseline only.

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Screening 
Period
(Within 
28 Days 
Prior to 
First 
Dose)
Treatment Period (1 cycle = 28 days)
Safety 
Follow-up
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
(±1d)
15
(±1d)
22
(±1d)
1 
(±3d)
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.
ECOG performance status
X
X
X
X
X
See Appendix A.
12-Lead Electrocardiogram
X
X
X
X
X
At screening and 2 hours (±15 minutes) 
after dosing on D1 of each cycle.
Hematology
X
X
X
X
X
X
X
X
Within 24 hours prior to treatment.
Coagulation
X
X
X
X
X
Within 24 hours prior to treatment at each 
timepoint, and as clinically indicated.
Chemistry (Serum or plasma)
X
X
(X)
X
X
X
X
X
X
Within 24 hours prior to treatment, on D1 
of each cycle and on D8, D15, and D22 of 
Cycle 1 only.  Additional collection to 
verify phosphorus levels on C1D4
(±24 hours).  More frequent assessments 
may be performed if clinically indicated.  
Pregnancy test
X
X
X
X
X
Serum pregnancy test required for women 
of child-bearing potential (WOCBP) at 
screening and end of treatment; serum or 
urine pregnancy test required at all other 
timepoints.
Tumor Assessments/Scans
X
see 
notes
X
(X)
At screening and at the end of every 
8 weeks/2 cycles (± 1 week). Note that 
patients who discontinue without PD 
should continue to undergo tumor 
assessments/scans according to this 
schedule until PD is documented, new 
anticancer therapy is initiated, the study is 
terminated, or consent is withdrawn.
Note that scans obtained prior to 
completion of the ICF may be used as the 
screening tumor scan if completed within 
28 days of first dose.

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Screening 
Period
(Within 
28 Days 
Prior to 
First 
Dose)
Treatment Period (1 cycle = 28 days)
Safety 
Follow-up
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
(±1d)
15
(±1d)
22
(±1d)
1 
(±3d)
ctDNA blood samples
X
see
notes
X
(X)
Collected prior to the first TAS-120
administration on C1D1, on D1 of each 
alternative uneven cycle (Cycle 3, 5, 7 and 
ongoing), at time of PD, and at the EOT
visit. 
Prior & concomitant medications, 
AE assessments
X
X
X
X
Collect from the time ICF is signed 
through 30 days after administration of the 
last dose of study therapy or until the start 
of new anticancer therapy.  Thereafter, 
only SAEs considered related to study 
therapy will be collected.
Survival status and subsequent 
therapy
X
After discontinuation of treatment, 
survival follow-up should occur every 
12 weeks (±2 weeks) until survival events 
(deaths) have been reported for 75% of 
enrolled patients or the study is terminated 
earlier by the Sponsor.
OPTIONAL: fresh tumor biopsy 
for pharmacodynamic assessment
X
see
notes
(X)
(X)
Baseline and at the end of Cycle 1 
(C1 D28 ± 7 days). It is strongly 
recommended to also obtain a fresh tumor 
sample at the time of disease progression.
Sample collection for PopPK 
Analysis
X
On Cycle 2 Day 1 only, PopPK samples 
will be collected within 1 hour prior to 
dosing and at 2 hours (±1 hour) and 
5 hours (at least 3 hours apart from 
sampling at 2 hours) post-dose
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. 
Fulvestrant Dosing 
(Cohort 4 ONLY)
X
X
X
Days 1 and 15 of Cycle 1 and Day 1 of all 
subsequent cycles, for patients in Cohort 4 
only.

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TABLE OF CONTENTS
OVERVIEW OF CHANGES ..........................................................................................................2
TABLE OF CONTENTS...............................................................................................................13
LIST OF TABLES.........................................................................................................................18
LIST OF FIGURES .......................................................................................................................18
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS................................................19
1.
INTRODUCTION......................................................................................................21
1.1.
Disease Background and Study Population................................................................21
1.2.
TAS-120 .....................................................................................................................21
1.2.1.
Background and Nonclinical Overview......................................................................21
1.2.2.
Clinical Overview.......................................................................................................22
1.3.
Summary of Study Rationale......................................................................................23
2.
OBJECTIVES AND ENDPOINTS............................................................................24
3.
INVESTIGATIONAL PLAN.....................................................................................26
3.1.
Overview of Study Design..........................................................................................26
3.2.
Study Periods and Visits for Each Patient ..................................................................27
3.2.1.
Screening Period.........................................................................................................28
3.2.2.
Patient Enrollment ......................................................................................................28
3.2.3.
Treatment Period and End of Treatment Visit............................................................29
3.2.4.
Safety Follow-Up Period and 30-Day Safety Follow-Up Visit..................................29
3.2.5.
Post-Discontinuation Disease Assessment .................................................................29
3.2.6.
Survival Follow-Up ....................................................................................................29
3.3.
Study Completion and Study Extension.....................................................................29
3.4.
Randomization and Blinding......................................................................................30
4.
SELECTION AND WITHDRAWAL OF PATIENTS..............................................31
4.1.
Inclusion Criteria ........................................................................................................31
4.2.
Exclusion Criteria.......................................................................................................33
4.3.
Screen Failure .............................................................................................................34
4.4.
Discontinuation of Treatment.....................................................................................34
4.5.
Discontinuation from the Study..................................................................................35
5.
STUDY TREATMENT..............................................................................................36

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5.1.
Study Drug Administration.........................................................................................36
5.1.1.
TAS-120 .....................................................................................................................36
5.1.2.
Fulvestrant ..................................................................................................................36
5.1.3.
Treatment Duration.....................................................................................................36
5.2.
Definition of a Dose-Limiting Toxicity (Cohort 4 Only)...........................................36
5.3.
Dose and Schedule Modifications ..............................................................................38
5.3.1.
Dose and Schedule Modifications for TAS-120.........................................................38
5.3.1.1.
General Considerations...............................................................................................38
5.3.1.2.
Dose Modifications for Nonhematologic Toxicities ..................................................38
5.3.1.3.
Dose Modifications for Hematologic Toxicities ........................................................41
5.3.1.4.
Adverse Event Follow-Up ..........................................................................................41
5.3.2.
Dose and Schedule Modifications for Fulvestrant......................................................42
5.4.
Treatment Compliance................................................................................................42
5.5.
Concomitant Medications and Therapies ...................................................................43
5.5.1.
Drug Interactions ........................................................................................................43
5.5.2.
Prohibited Medications and Therapies .......................................................................44
5.6.
Effective Contraception During Study .......................................................................44
5.7.
Study Drug Materials and Management.....................................................................45
5.7.1.
Description of Study Drug..........................................................................................45
5.7.1.1.
TAS-120 .....................................................................................................................45
5.7.1.2.
Fulvestrant ..................................................................................................................45
5.7.2.
Packaging and Labeling..............................................................................................45
5.7.3.
Study Drug Storage.....................................................................................................46
5.7.4.
Drug Accountability ...................................................................................................46
6.
STUDY ASSESSMENTS ..........................................................................................47
6.1.
Study Assessments and Procedures............................................................................47
6.1.1.
Determination of FGFR1 or FGFR2 Amplification Status........................................47
6.1.1.1.
High-Level FGFR1 Amplification .............................................................................47
6.1.1.2.
FGFR2 amplification..................................................................................................47
6.1.2.
General Assessments ..................................................................................................47
6.1.3.
Ophthalmological Examination..................................................................................48
6.1.4.
Laboratory Assessments .............................................................................................48

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6.1.5.
Tumor Assessments/Scans..........................................................................................49
6.1.6.
Safety Evaluations ......................................................................................................49
6.1.7.
Pharmacodynamic Evaluations...................................................................................49
6.1.8.
Pharmacokinetic Evaluations......................................................................................49
6.1.9.
Survival Follow-Up ....................................................................................................50
7.
EFFICACY EVALUATIONS....................................................................................51
7.1.
Efficacy Criteria..........................................................................................................51
7.1.1.
Method of Imaging .....................................................................................................51
7.1.2.
Tumor Definitions ......................................................................................................51
7.2.
Efficacy Endpoints......................................................................................................53
7.2.1.
Response Criteria........................................................................................................53
7.2.1.1.
Target and Non-Target Response Assessments..........................................................54
7.2.1.2.
Objective Response Assessment.................................................................................55
8.
SAFETY INFORMATION ........................................................................................56
8.1.
Adverse Events ...........................................................................................................56
8.1.1.
Definitions of Adverse Events....................................................................................56
8.1.2.
Reporting of Adverse Events......................................................................................56
8.1.2.1.
Terms of Reported Adverse Events............................................................................56
8.1.2.2.
Severity of Adverse Events ........................................................................................56
8.1.2.3.
Causal Relationship with Study Drug.........................................................................57
8.1.2.4.
Outcome of Adverse Events.......................................................................................57
8.1.2.5.
Follow-up of Adverse Events .....................................................................................57
8.2.
Serious Adverse Events..............................................................................................58
8.2.1.
Definitions of Serious Adverse Events.......................................................................58
8.2.2.
Reporting of Serious Adverse Events (within 24 hours)............................................58
8.2.3.
Reporting of Deaths....................................................................................................59
8.2.4.
Follow-up of Serious Adverse Events ........................................................................59
8.3.
Disease Progression....................................................................................................60
8.4.
Laboratory Assessments .............................................................................................60
8.4.1.
Reporting and Evaluation of Laboratory Test Results ...............................................60
8.4.2.
Repeat Testing ............................................................................................................60
8.5.
Other Safety Information............................................................................................60

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8.5.1.
Pregnancy ...................................................................................................................60
8.5.2.
Overdose.....................................................................................................................61
8.5.3.
Medication Errors .......................................................................................................61
9.
PHARMACODYNAMIC AND PHARMACOKINETIC EVALUATION ..............62
9.1.
Pharmacodynamic and Biomarker Assessments ........................................................62
9.1.1.
Objectives and Background........................................................................................62
9.1.2.
Assessment of FGF/FGFR Aberrations in Blood ......................................................62
9.1.3.
Tumor Biopsy.............................................................................................................62
9.2.
Population Pharmacokinetic Sample Collection and Analysis...................................63
10.
STATISTICS ..............................................................................................................64
10.1.
Estimation of Sample Size..........................................................................................64
10.2.
Planned Interim Analysis............................................................................................64
10.3.
Analysis Populations ..................................................................................................65
10.4.
Criteria for Handling of Patient Data..........................................................................65
10.5.
Statistical Analyses.....................................................................................................66
10.5.1.
Demographic and Baseline Characteristics ................................................................66
10.5.2.
Efficacy Analyses .......................................................................................................66
10.5.3.
Safety Analyses ..........................................................................................................67
10.5.4.
Pharmacokinetic Analysis ..........................................................................................67
10.5.5.
Pharmacodynamic/Biomarker Analysis .....................................................................68
11.
ADMINISTRATIVE CONSIDERATIONS ..............................................................69
11.1.
Protocol Compliance ..................................................................................................69
11.2.
Protocol Deviations ....................................................................................................69
11.3.
Protocol Amendments ................................................................................................69
11.4.
Study Termination ......................................................................................................69
11.5.
Post-trial Provisions....................................................................................................69
11.6.
Case Report Forms .....................................................................................................70
11.7.
Access to Source Data/Documents.............................................................................70
11.7.1.
Source Data/Documents .............................................................................................70
11.7.2.
Source Data Verification ............................................................................................70
11.8.
Data Handling.............................................................................................................70
11.9.
Responsibilities of Recordkeeping .............................................................................71

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11.9.1.
Investigator and Study Site.........................................................................................71
11.9.2.
Sponsor .......................................................................................................................71
11.10.
Monitoring..................................................................................................................71
11.11.
Financial Disclosure ...................................................................................................71
11.12.
Compensation for Health Injury.................................................................................71
12.
QUALITY CONTROL AND QUALITY ASSURANCE .........................................72
12.1.
Quality Control ...........................................................................................................72
12.2.
Quality Assurance.......................................................................................................72
13.
ETHICS ......................................................................................................................73
13.1.
Ethical Conduct of the Study......................................................................................73
13.2.
Written Informed Consent..........................................................................................73
13.3.
Institutional Review Board/Independent Ethics Committee ......................................73
14.
PUBLICATION POLICY ..........................................................................................74
14.1.
Publication Policy.......................................................................................................74
15.
LIST OF REFERENCES............................................................................................75
16.
SIGNATURES OF SPONSOR AND PRINCIPAL INVESTIGATOR.....................76
APPENDIX A.
ECOG PERFORMANCE STATUS..................................................................78
APPENDIX B.
DIETARY GUIDELINES FOR TREATMENT OF 
HYPERPHOSPHATEMIA ........................................................................................79
APPENDIX C.
CHILD-PUGH SCORE.....................................................................................80
APPENDIX D.
CLASSIFICATION OF SUBSTRATES, INHIBITORS, AND 
INDUCERS OF CYP ENZYMES AND TRANSPORTERS ....................................81

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LIST OF TABLES
Table 1:
Schedule of Events .....................................................................................................10
Table 2:
Objectives and Endpoints ...........................................................................................24
Table 3:
Dose Limiting Toxicity Definition.............................................................................37
Table 4:
TAS-120 Dosing Modification for Related Nonhematologic Toxicities ...................39
Table 5:
Recommendations for Hyperphosphatemia Management..........................................40
Table 6:
TAS-120 Dose Interruption and Modification Criteria for Related 
Hematologic Toxicities...............................................................................................41
Table 7:
Required Follow-up for Adverse Events ....................................................................42
Table 8:
TAS-120 Product Description and Packaging Information........................................45
Table 9:
Efficacy Endpoints......................................................................................................53
Table 10:
Target and Non-target Lesions ...................................................................................54
Table 11:
Time Point Response for Patients with Target (±Non-target) Disease.......................55
Table 12:
Time Point Response for Patients with Only Non-target Disease..............................55
Table 13:
Analysis Populations ..................................................................................................65
Table 14:
Efficacy Endpoint Definitions....................................................................................66
LIST OF FIGURES
Figure 1.
Antitumor effect of TAS-120 against a human mammary carcinoma MFM-
223 xenograft model...................................................................................................22
Figure 2.
Study design flow chart ..............................................................................................26
Figure 3.
Overview of study periods and visits..........................................................................28

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Term
Definition
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANC
absolute neutrophil count
ASCO
American Society of Clinical Oncology
AST
aspartate aminotransferase
AUC
area under the plasma concentration time curve
BCRP
breast cancer resistance protein
CAP
College of American Pathologists
CBR
clinical benefit rate
CCA
cholangiocarcinoma
Ccr
creatinine clearance
CI
confidence interval
CLIA
Clinical Laboratory Improvement Amendments
cPR
confirmed partial response
CR
complete response
CT
computed tomography
ctDNA
circulating tumor DNA
CYP
Cytochrome P450
DCR
disease control rate
DLT
dose-limiting toxicity
DOR
duration of response
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EDC
electronic data capture
EOT
end-of-treatment
ER
estrogen receptor
FGF
fibroblast growth factor
FGFR
fibroblast growth factor receptor
FISH
fluorescence in situ hybridization
GCP
Good Clinical Practice
GI50
50% cell growth-inhibitory concentration
GnRH
gonadotropin-releasing hormone
HER2
human epidermal growth factor receptor 2
HR
hormone receptor
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
independent ethics committee

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Term
Definition
IM
intramuscular
IRB
institutional review board
MRI
magnetic resonance imaging
NCI-CTCAE
National Cancer Institute - Common Terminology Criteria for Adverse Events
NGS
next-generation sequencing
ORR
objective response rate
OS
overall survival
PD
progressive disease
PFS
progression-free survival
P-gp
P-glycoprotein
PI
prescribing information
PK
pharmacokinetics
PO
oral
PopPK
population pharmacokinetics
PR
partial response OR progesterone receptor
QD
daily
QTcF
corrected QT interval using Fridericia's formula
RECIST
Response Evaluation Criteria in Solid Tumors
SAE
serious adverse event
SAP 
Statistical Analysis Plan
SD
stable disease
SOP
Standard Operating Procedures
TID
three times per day
TNBC
triple negative breast cancer
TOI
Taiho Oncology, Inc.
ULN
upper limit of normal
WOCBP
women of child-bearing potential

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1.
INTRODUCTION
1.1.
Disease Background and Study Population
The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling axis has
been well characterized for its role in proliferation, differentiation, migration, and survival of cells, 
and it is fundamental to embryonic development, regulation of angiogenesis, and wound healing in 
adults. 
Activating FGFR genomic aberrations are reported in various cancers including breast cancer, 
with a reported incidence of 18% (Helsten 2016).  FGFR gene amplifications are the most 
frequently observed abnormality, with FGFR2 gene amplifications observed in approximately 2% 
of all invasive breast cancers and FGFR1 gene amplifications observed in approximately 10% of 
all invasive breast cancers, predominantly in the hormone receptor positive (HR+) breast cancers 
(Jain and Turner 2012, Turner et al. 2010). 
The reported incidence of FGFR2 gene amplification is approximately 1.5% in HR+ breast cancer, 
2%-4% in triple negative breast cancer (TNBC) and 1% in human epidermal growth factor 
receptor 2 positive (HER2+) breast cancer (Razavi et al. 2018; Jain and Turner 2012, Turner 
2013).
1.2.
TAS-120
1.2.1.
Background and Nonclinical Overview
TAS-120 is a novel and selective small molecule FGFR inhibitor, which is the first irreversible, 
covalent inhibitor of FGFR1–4 being tested in humans.  TAS-120 selectively and irreversibly
binds to FGFR to exert an inhibitory effect on the FGF/FGFR pathway.
The in vitro efficacy of TAS-120 against human breast carcinoma cell lines was evaluated in 
2 nonclinical studies.  In these studies, TAS-120 markedly inhibited the proliferation of breast 
cancer cell lines with FGFR1 amplifications; the 50% cell growth-inhibitory concentration (GI50) 
was 0.00078 ± 0.00012 µmol/L for MFM-223 cells and 0.056 ± 0.029 µmol/L for 
MDA-MB-134-VI cells.  By contrast, the GI50 values for breast cancer cell lines not displaying 
FGFR1 amplifications (SK-BR-3 and MCF-7) were 6.7 ± 3.3 µmol/L and 9.1 ± 3.4 µmol/L, 
respectively. 
In vivo studies showed that TAS-120 has 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 particular, a multi-dose (range 6.3 – 50 mg/kg/day) 
study was performed to determine the efficacy of oral (PO) administration of TAS-120 to mice 
implanted with MFM-223 human breast tumor fragments harboring FGFR1 gene amplification.  
In this study, TAS-120 completely suppressed the growth of MFM-223 tumors, especially at doses 
of 25 and 50 mg/kg/day (Figure 1).

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Notes:
Each plot and bar indicate the mean and standard deviation, respectively (n = 6).
* p < 0.05 in the TAS-120-treated group as compared with the vehicle control group by Dunnett’s test.
Figure 1.
Antitumor effect of TAS-120 against a human mammary carcinoma MFM-223 
xenograft model
1.2.2.
Clinical Overview
On the basis of encouraging in vitro and in vivo data, excerpted above and outlined in full in the 
Investigator’s Brochure, a clinical development program was initiated for TAS-120. To date, 
2 clinical studies have been completed: 1 bioequivalence study assessing 2 dosage forms, and 
1 food effect study.  Two studies assessing the safety, efficacy, and pharmacokinetics (PK) of 
TAS-120 in advanced cancers are currently ongoing: Study 10059010, a 2-step Phase 1 trial in 
45 Japanese patients with advanced solid tumors, and Study TAS-120-101, a Phase 1/2 trial in 
three parts:

A Phase 1 Dose Escalation portion (now complete with a total of 86 patients receiving 
either daily or every-other-day dosing);

A Phase 1 Dose Expansion portion, which includes additional cohorts in 
cholangiocarcinoma (CCA), gliomas, urothelial carcinoma, and basket cohorts with 
FGF/FGFR aberrations; and

A Phase 2 study initiated in April 2018, evaluating TAS-120 at a daily (QD) dose of 
20 mg, in patients with CCA harboring FGFR2 gene fusions.
The Phase 2 portion of this study was initiated based on strong evidence of antitumor activity in 
CCA in the Phase 1 portions.  Forty-five patients with CCA harboring FGF/FGFR aberrations 
were treated at 16 mg, 20 mg, and 24 mg QD.  Twenty-eight patients (62%) had FGFR2 gene 
fusions; of these 28 patients, 20 (71%) experienced tumor shrinkage and seven achieved 
confirmed partial response (cPR).  The objective response rate (ORR) was 25%, and the overall 
disease control rate (DCR) was 79%.  Of 17 patients with other FGF/FGFR aberrations, three had 

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cPR (two with FGFR2 re-arrangement and one with co-expression of FGFR2 re-arrangement and 
amplification) (Meric-Bernstam et al. 2018).
In addition, durable responses were observed in Studies 10059010 and TAS-120-101 in 2 patients 
with advanced breast cancer harboring FGFR2 gene amplifications. Specifically, a patient with 
TNBC and a patient with HR+ HER2+ breast cancer both achieved a cPR.  
Collectively, safety data from clinical trials suggest that TAS-120 is tolerable to patients with
advanced cancers.  The most frequently reported treatment-related adverse event (AE) overall has 
been hyperphosphatemia, mostly of National Cancer Institute – Common Terminology Criteria for 
Adverse Events (NCI-CTCAE) Grades 1-2 and without clinical complications.  Other frequently 
reported treatment-related AEs included the gastrointestinal system disorders of diarrhea, dry 
mouth, nausea, and stomatitis. Dry skin and increased liver enzymes were also reported, most of 
which were mild to moderate in severity.
Safety concerns that have been identified from preclinical studies of TAS-120 include an increase 
of inorganic phosphorus in plasma, ectopic mineralization in various organs and tissues, lesions in 
bone/cartilage, and corneal lesions. An embryo-fetal developmental toxicity study conducted in 
rats showed that TAS-120 inhibited normal development of the rat embryo-fetus and resulted in 
embryo-fetal lethality.  Effective contraception is mandated for any patients receiving TAS-120
who are of child bearing potential and their partners.
1.3.
Summary of Study Rationale
FGFR gene mutations, particularly amplifications, play an important role in the development of 
breast cancer; FGFR1 and FGFR2 gene amplifications are present in approximately 10% and 2%, 
respectively, of all invasive breast cancers.  TAS-120, an inhibitor of FGFR1-4, has shown 
promising preclinical activity in the treatment of breast cancers and other cancer types; in a 
Phase 1 clinical study, TAS-120 monotherapy was associated with 2 durable PRs in patients with 
treatment-refractory breast cancer. 
Accordingly, this Phase 2 study will include patients with breast cancer harboring FGFR gene 
amplifications.  Recent evidence suggests that the addition of an FGFR inhibitor may overcome 
resistance to hormonal therapy in breast cancer (Turner et al. 2010).  Accordingly, patients in this 
study will receive either single-agent TAS-120 or combination treatment comprising TAS-120 and 
fulvestrant. 
A safety lead-in will be performed for the combination of TAS-120 and fulvestrant to assess any 
overlapping or exacerbated toxicities with adjustment of the dose of TAS-120 if required.
The maximum tolerated dose of TAS-120 is 20 mg QD (continuous daily dosing), based on the 
results of the Phase 1 dose escalation portion of Study TAS-120-101. Accordingly, the starting 
dose of TAS-120 in this Phase 2 study will be 20 mg QD.
Population plasma PK samples will be obtained to explore PK of TAS-120 by population 
pharmacokinetic (PopPK) analysis and exposure-response analyses.

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2.
OBJECTIVES AND ENDPOINTS
The objectives and endpoints of this study are shown in Table 2.
Table 2:
Objectives and Endpoints
Primary
The primary objective of this study is to assess the antitumor activity of TAS-120 as monotherapy or in 
combination with fulvestrant in the treatment of patients with metastatic breast cancer harboring FGFR
amplifications, as measured by:  

ORR in patients with centrally confirmed 
FGFR2 amplification and measurable disease 
(Cohorts 1, 2);
ORR, defined as the proportion of patients with a 
confirmed response of either complete response 
(CR) or partial response (PR) per Investigator
assessment.

Clinical benefit rate (CBR) in patients with 
centrally confirmed FGFR2 amplification and 
nonmeasurable, evaluable disease (Cohort 3); 
and
CBR, defined as the proportion of patients with a 
confirmed response of CR, or stable disease (SD) 
lasting at least 24 weeks, per Investigator
assessment.

6-month progression-free survival (PFS) rate 
in patients with centrally confirmed high level 
FGFR1 amplification and measurable disease 
(Cohort 4).
6-month PFS rate, defined as the proportion of 
patients who are alive and progression-free 
6 months after the first dose of study therapy.
Secondary
The secondary objectives of this study are:

To determine the CR rate in Cohort 3, the 
ORR in Cohort 4, the CBR in Cohorts 1, 2, 
and 4, and the 6-month PFS rate in Cohorts 
1-3;
ORR, CR rate, CBR, and 6-month PFS rate, as 
defined above; CBR will include PR in these 
cohorts.

To evaluate the duration of response (DOR) 
among patients with objective response in any 
cohort;
DOR, defined as the time from first 
documentation of objective response to the date 
of death (any cause) or disease progression per 
Investigator assessment.

To evaluate the PFS and overall survival (OS) 
in all cohorts; and
PFS, defined as the time from first dose of study 
therapy to the date of death (any cause) or disease 
progression per Investigator assessment.
OS, defined as the time from first dose of study 
therapy to the date of death (any cause).

To investigate the safety of TAS-120 as 
monotherapy and in combination with 
fulvestrant.
Adverse events, graded according to the NCI-
CTCAE, Version 5.0.
Evaluation of dose-limiting toxicity (DLT) in 
Cohort 4 only.

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Exploratory
The exploratory objectives of this study are:

To investigate the downstream 
pharmacodynamic effects of treatment with 
TAS-120;
Changes in pharmacodynamic markers assessed 
in fresh tumor tissue biopsies.

To explore markers of response and 
mechanisms of resistance in tumor tissue 
biopsies and/or blood; and
Exploratory association of tissue and/or blood 
markers with tumor efficacy endpoints and/or 
tumor resistance to TAS-120.

To explore PK of TAS-120 by PopPK analysis 
and exposure-response analyses.
Estimation of individual PK parameters such as 
AUC and exploratory association of the exposure 
with clinical parameters.

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3.
INVESTIGATIONAL PLAN
3.1.
Overview of Study Design
This is a Phase 2, open-label, non-randomized, multicenter study designed to evaluate the efficacy 
and safety of TAS-120 and TAS-120 + fulvestrant in adult patients with locally 
advanced/metastatic breast cancer harboring FGFR gene amplifications. Up to approximately 
168 patients will be enrolled in this study, which will be conducted at approximately 75 sites
globally.
Patients will be enrolled to 1 of 4 treatment cohorts based on diagnosis and FGFR gene 
amplification status, and will receive either single agent TAS-120 in Cohorts 1-3 or TAS-120 plus 
fulvestrant in Cohort 4 (Figure 2). 
Figure 2.
Study design flow chart
In all cohorts, a treatment cycle is defined as 28 days.  All patients will receive PO TAS-120 at a 
dose of 20 mg QD (continuous daily dosing).  Patients in Cohort 4 only will also receive 
intramuscular (IM) fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and Day 1 of every 
subsequent cycle. Pre/peri-menopausal patients in Cohort 4 are required to also have ovarian 
suppression with goserelin as part of standard of care, having started a gonadotropin-releasing 
hormone (GnRH) analogue at least 4 weeks prior to the first dose of fulvestrant.
Treatment will continue until disease progression, unacceptable toxicity, or any other of the 
criteria for treatment discontinuation is met (Section 4.4). For patients who discontinue treatment
for reasons other than disease progression, tumor assessments should be continued until radiologic 
disease progression is documented or until initiation of subsequent new anticancer therapy 

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(whichever occurs first). Patients will be followed for survival every 12 weeks (±2 weeks) until 
survival events (deaths) have been reported for 75% of enrolled patients or the study is terminated 
early by the Sponsor.
Cohorts 1 and 2 will initially enroll a total of approximately 19 response-evaluable patients per 
cohort. If ≥4 responses (PR or CR) are observed in a cohort, that cohort will be further expanded 
to a total of approximately 55 response-evaluable patients.
Cohort 3 will initially enroll a total of approximately 9 response-evaluable patients. If ≥3 patients 
experience clinical benefit (CR, or SD ≥24 weeks) are observed, the cohort will be further 
expanded to a total of approximately 24 response-evaluable patients.
Because the combination of TAS-120 and fulvestrant has not been assessed in patients, Cohort 4
will begin with a safety lead-in period.  During the safety lead-in, 3 patients will initially be 
enrolled and will receive TAS-120 (20 mg QD) and fulvestrant (500 mg) according to the study 
schedule, with safety follow-up of at least 1 cycle. Patients will be assessed for DLTs and the 
recommended dose of TAS-120 for this cohort will be determined as follows.

Of the initial 3 patients, if 0/3 or 1/3 patients present with a DLT, another 3 patients will be 
enrolled.
o
If 0/6 or 1/6 patients present with a DLT, the safety lead-in phase will conclude and 
enrollment will continue to a total of 28 patients treated with TAS-120 (20 mg QD) 
plus fulvestrant.

If ≥2/3 or ≥2/6 patients present with a DLT, TAS-120 20 mg QD plus fulvestrant will be 
defined as a non-tolerated dose level for the combination. Subsequent patients will be 
treated at a dose of TAS-120 of 16 mg QD plus fulvestrant, and the sequence will be 
repeated. Initially, 3 patients will be enrolled:
o
If 0/3 or 1/3 patients present with a DLT, another 3 patients will be enrolled.

If 0/6 or 1/6 patients present with a DLT, the safety lead-in phase will 
conclude and enrollment will continue to a total of 28 patients treated with
TAS-120 (16 mg QD) plus fulvestrant.
o
If ≥2/3 or ≥2/6 patients present with a DLT at the dose of TAS-120 at 16 mg QD 
plus fulvestrant, the assessment of the combination and further enrollment to 
Cohort 4 will be discontinued.
3.2.
Study Periods and Visits for Each Patient
The study periods / visits described in this section are defined for all patients, and summarized in 
Figure 3.  Please note:

For all patients, the Safety Assessment Period begins at the time the informed consent form
(ICF) is signed for the study (that is, the beginning of the Screening Period) and continues
until at least 30 days after the last day of study therapy (that is, the end of the Safety 
Follow-up Period).  After the 30-day Safety Follow-Up Visit (see below), patients will be 
assessed for drug-related serious adverse events (SAEs) only.

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
For each patient, the Study Duration is defined as the time from day of ICF signature to the 
last day of Disease Assessment Follow-up / Survival Follow-up (see below).
No protocol-specific procedures or assessments may be performed prior to completion of the ICF, 
except for those that represent standard-of-care.
Abbreviations: C=Cycle; D=Day; d=days; EOT=end-of-treatment; FU=follow-up; PD=progressive 
disease; Tx=treatment.
Figure 3.
Overview of study periods and visits
3.2.1.
Screening Period
The Screening Period is defined as the time from the time the patient completes the ICF form until 
the date and time of first dose of study therapy.  Unless otherwise described in the Schedule of 
Events (Table 1), all screening assessments must be performed within 28 days prior to the first 
dose of study therapy.  
Determination of eligibility is based on the entry criteria enumerated in Section 4, including 
determination of FGFR1 or FGFR2 amplification status per the methods described in 
Section 6.1.1 of this protocol. 
3.2.2.
Patient Enrollment
Once the ICF is signed, the patient will be assigned a unique patient identification number.  Once 
study eligibility is confirmed, the patient will be enrolled into the appropriate treatment cohort.

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3.2.3.
Treatment Period and End of Treatment Visit
Treatment discontinuation may occur for any of the reasons listed in Section 4.4.  The treatment 
period is the time from the date of first dose of study therapy (Day 1) to the date of last dose of 
study therapy.  An end-of-treatment (EOT) visit must be performed within 7 days after the 
decision is made to discontinue study treatment; at this visit, every effort should be made to 
perform the assessments outlined in Table 1. 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.
3.2.4.
Safety Follow-Up Period and 30-Day Safety Follow-Up Visit
The safety follow-up period is the time from the date of last dose of study therapy through the 
30-day safety follow-up visit, which must be performed 30 days (±3 days) following the last dose 
of study therapy.  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. Every effort should be made to perform the assessments outlined in Table 1.  If the 
patient is unable to return to the study site, a follow-up phone call can be made by the study site to 
collect any new safety information that occurred during the Safety Follow-up Period.
After the 30-day Safety Visit, only AEs that are serious and drug-related will be assessed.
3.2.5.
Post-Discontinuation Disease Assessment
Patients who discontinue without documented disease progression should continue to undergo 
tumor assessments/scans according to the Schedule of Events (that is, every 12 weeks ±7 days
until progressive disease (PD) is documented, new anticancer therapy is initiated, the study is 
terminated, or the patient dies, withdraws consent, or is lost to follow-up).
3.2.6.
Survival Follow-Up
Once disease progression is confirmed or the first subsequent new breast cancer therapy is 
initiated, whichever occurs first, the survival follow-up period begins.  During this period, the 
patient or family should be contacted for survival follow-up every 12 weeks (±2 weeks) until 
withdrawal of consent, death, or loss to follow up, until survival events (deaths) have been 
reported for 75% of enrolled patients or the study is terminated earlier by the Sponsor.  In addition, 
all subsequent breast cancer treatments will be recorded.
3.3.
Study Completion and Study Extension
The study will be considered complete when:

Survival events (deaths) have been reported for 75% of enrolled patients; or

The trial is halted early for any reason.

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Following Study Completion, patients still receiving and deriving benefit from study therapy in 
the opinion of the Investigator and Sponsor will be permitted to continue treatment in a Study 
Extension phase. During the Study Extension, patients may receive treatment until withdrawal 
criteria are met.  During this period, limited information will be collected as follows (including but 
not limited to): 

Study drug administration;

Study drug accountability;

Serious adverse events;

Non-serious adverse events that are related to study treatment or result in treatment 
discontinuation; and

Any cases of pregnancy, overdose, or medication error.
3.4.
Randomization and Blinding
This is an open-label, non-randomized study.

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4.
SELECTION AND WITHDRAWAL OF PATIENTS
Determination of FGFR amplification status should be completed before the patient undergoes any 
other protocol-specific procedures. Patients must have either HR+ HER2- breast cancer or TNBC 
harboring an FGFR2 amplification, or HR+ HER2- breast cancer harboring an FGFR1 high-level 
amplification (Section 6.1.1).  
Waivers will not be granted for any of the eligibility criteria.
4.1.
Inclusion Criteria
A patient must meet all of the following inclusion criteria to be eligible for this study.  
1.
Patient provides written informed consent.
2.
Patient is ≥18 years of age (or meets the country’s regulatory definition for legal adult age, 
whichever is greater)
3.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
4.
Histologically or cytologically confirmed recurrent locally advanced or metastatic breast 
cancer not amenable to treatment with curative intent, meeting all of the criteria for 1 of the 
following cohorts: 
A. Cohort 1
i.
HR+ HER2- breast cancer harboring an FGFR2 gene amplification.  HR+ 
HER2- breast cancer is defined per the local pathology report as estrogen 
receptor (ER) >1% and/or progesterone receptor (PR) >1%, HER2-negative per 
American Society of Clinical Oncology (ASCO) and the College of American 
Pathologists (CAP) guidelines, 2018.
ii.
Measurable disease per Response Evaluation Criteria in Solid Tumors 
(RECIST) Version 1.1
iii.
Has received 1-3 prior endocrine-containing therapies and up to 2 prior 
chemotherapy regimens for advanced/metastatic disease
iv.
Has received prior treatment with a CDK4/6 inhibitor or is ineligible for such 
treatment (per Investigator decision)
v.
Has experienced disease progression/recurrence within 1 month following the 
completion of any endocrine therapy for advanced/metastatic breast cancer
B. Cohort 2
i.
TNBC harboring an FGFR2 gene amplification. TNBC is defined as negative 
for ER, PR and HER2. Negative for ER and PR includes the following: local 
pathology report classifies them as negative, Allred Score of 2 or below or <1% 
staining. HER2-negative per ASCO / CAP guidelines, 2018.
ii.
Measurable disease per RECIST 1.1
iii.
Has received at least 1 prior chemotherapy or chemotherapy/immunotherapy 
(PD-L1/PD-1 inhibitors) regimen for advanced/metastatic disease
iv.
Has experienced disease progression/recurrence during or after the most recent 
prior chemotherapy for advanced/metastatic breast cancer

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C. Cohort 3
i.
TNBC or HR+ HER2- breast cancer (defined as above) harboring an FGFR2
gene amplification 
ii.
Non-measurable, evaluable disease per RECIST 1.1. Patients with bone-only 
disease must have lytic or mixed lytic-blastic lesions
iii.
Other criteria for either HR+ HER2- breast cancer or TNBC should be met as 
described for Cohort 1 and 2, respectively
D. Cohort 4
i.
HR+ HER2- breast cancer (defined as above) harboring an FGFR1 high-level
gene amplification as defined in Section 6.1.1.1
ii.
Measurable disease per RECIST 1.1
iii.
Has received 1-2 prior endocrine-containing therapies and no more than 1 prior 
chemotherapy regimen for advanced/metastatic disease. Prior treatment with 
fulvestrant is not permitted.
iv.
Has received prior treatment with a CDK4/6 inhibitor or is ineligible for such 
treatment (per Investigator decision)
v.
Pre/peri-menopausal patients must be on goserelin. Patients must have 
commenced treatment with goserelin or an alternative GnRH agonist at least 
4 weeks prior to the first dose of fulvestrant. If patients have received an 
alternative GnRH agonist prior to study entry, they must switch to goserelin for 
the duration of the trial.  Postmenopausal is defined as at least one of the 
following criteria: age ≥60 years; age <60 years and cessation of regular menses 
for at least 12 consecutive months with no alternative pathological or 
physiological cause; and serum estradiol and follicle-stimulating hormone level 
within the laboratory’s reference range for postmenopausal females; or 
documented bilateral oophorectomy.
vi.
Has experienced disease progression/recurrence within 1 month following the 
completion of any endocrine therapy for advanced/metastatic breast cancer.
5.
Archival or (preferably) fresh tumor tissue must be available for central laboratory 
confirmation of FGFR amplification.
6.
The patient is able to take medications orally (a feeding tube is not permitted).
7.
The patient has adequate organ function as defined by the following criteria:
a.
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × the 
upper limit of normal (ULN); if liver function abnormalities are due to underlying liver 
metastases, AST and ALT ≤5 × ULN
b. Total bilirubin ≤1.5 × ULN or ≤3 × ULN in case of Gilbert’s syndrome
c.
Absolute neutrophil count (ANC) ≥1.0 × 109/L without hematopoietic growth factor 
support 
d. Platelet count ≥75 × 109/L without transfusion support (that is, excluding 
measurements obtained within 3 days after transfusion of platelets)
e.
Hemoglobin ≥9.0 g/dL without transfusion support (that is, excluding measurements 
within 7 days after transfusion of packed red blood cells or whole blood)
f.
Serum phosphorus ≤ ULN

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g. Creatinine clearance (calculated or measured value): ≥40 mL/min
8.
Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test 
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 above. Both males and females of reproductive potential must agree to use 
effective birth control during the study prior to the first dose and for 90 days after the last 
dose of TAS-120 and 1 year after last dose of fulvestrant (Cohort 4 only).
9.
The patient is willing and able to comply with scheduled visits and study procedures.
4.2.
Exclusion Criteria
A patient must not meet any of the following exclusion criteria to be eligible for this study:
10. History and/or current evidence of any of the following disorders:
a.
Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered 
clinically significant in the opinion of the Investigator
b. Ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, 
intestine, or myocardia and lung, considered clinically significant in the opinion of the 
Investigator
c.
Retinal or corneal disorder confirmed by retinal/corneal examination and considered 
clinically significant in the opinion of the Investigator.
11. Corrected QT interval using Fridericia’s formula (QTcF) >470 msec. Patients with an 
atrioventricular pacemaker or other condition (for example, right bundle branch block) that 
renders the QT measurement invalid are an exception and the criterion does not apply.
12. Treatment with any of the following within the specified time frame prior to the first dose 
of TAS-120:
a.
Major surgery within 4 weeks (the surgical incision should be fully healed)
b. Radiotherapy for extended field within 4 weeks or limited field radiotherapy within 
2 weeks
c.
Any prior systemic therapy regardless of the stop date, but the patient must have 
recovered to eligibility levels from prior toxicity
d. Any investigational agent received within 30 days or 5 half-lives (whichever is shorter)
13. Prior treatment with an FGFR inhibitor
14. Cohort 4 only: Prior treatment with fulvestrant, or known hypersensitivity to fulvestrant.
15. A serious illness or medical condition(s) including but not limited to the following:
a.
Known acute systemic infection
b. Myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure 
within the previous 6 months
c.
History or current evidence of serious uncontrolled ventricular arrhythmia
d. Chronic diarrhea diseases considered to be clinically significant in the opinion of the 
Investigator

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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 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
16. Brain metastases that are untreated or clinically or radiologically unstable (that is, have 
been stable for <1 month)
17. History of another primary malignancy that is currently clinically significant or currently 
requires active intervention
18. Pregnant or lactating female
4.3.
Screen Failure
Screen failures are defined as patients who consent to participate in any portion of the clinical 
study but are not subsequently enrolled in the study. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure patients to Regulatory Authorities. 
Minimal information includes demography, screen failure details, eligibility criteria, and any SAE 
occurring after completion of the ICF.  Patients who do not meet the criteria for participation in 
this study (screen failure) may be rescreened a maximum of 2 times. 
4.4.
Discontinuation of Treatment
A patient may be discontinued from all study therapy for any of the following reasons: 
1. Disease progression based on RECIST 1.1;
2. Clinical disease progression per Investigator judgement;
3. Unacceptable AEs, or change in underlying condition such that the patient can no longer 
tolerate therapy, as evidenced by a dose delay > 28 days from the scheduled start date of 
the next cycle or need for more than the allowable number of dose reductions outlined in 
this protocol;
4. 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 followed in the 
study;
5. Pregnancy;
6. A significant protocol deviation which, in the opinion of the Investigator and/or Sponsor, 
renders the patient unsuitable for further study treatment;
7. Loss to follow-up;
8. Death;
9. Termination of the study by the Sponsor; or
10. At the patient’s request at any time irrespective of the reason. 

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Patients who withdraw consent for further treatment (treatment discontinuation criterion #10) may
choose to remain on study; in such a case, all study evaluations should continue as outlined in this
protocol.  If the patient withdraws consent to all follow-up, the patient should be considered to
have discontinued the study as described in Section 4.5.
The primary reason for discontinuation should be documented in the electronic case report form
(eCRF).
If there is strong evidence of clinical benefit and reasons to justify continuation of the study drug, 
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.
4.5.
Discontinuation from the Study
A patient may be discontinued from all study interventions and assessments (that is, discontinued 
from the study without follow-up) for any of the following reasons: 
1. Death;
2. Loss to follow-up / contact despite best effort of investigative site personnel (that is, after 
at least 2 documented attempts to contact the patient and/or family); or
3. Patient withdrawal of consent to further follow-up, irrespective of the reason.

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5.
STUDY TREATMENT
5.1.
Study Drug Administration
5.1.1.
TAS-120
A treatment cycle is defined as 28 days; however, TAS-120 is dosed continuously every day with 
no planned interruption between cycles.
TAS-120 is supplied as 4-mg tablets and will be taken PO at a dose of 20 mg QD in Cohorts 1, 2, 
and 3.  In Cohort 4, TAS-120 will be taken PO at a dose of 20 or 16 mg QD, depending on the 
DLT observations in the safety lead-in phase. 
TAS-120 should be taken under fasting conditions. It will be taken with a glass of water, on an 
empty stomach, every 24 hours in the morning or evening at the same time each day, if possible. 
No food should be consumed for 2 hours prior and 1 hour after the dose of TAS-120, but patients 
will be permitted to drink water during this period. 
In the event of a dosing delay up to 12 hours after the scheduled dosing time, the patient should 
still take that day’s dose.  If the dosing delay continues for >12 hours after the scheduled dosing 
time, or if the patient vomits after a dose, the patient should skip dosing for that day and not make 
up for it the following day.
Please note: dietary restrictions that limit phosphate intake may reduce the risk of 
hyperphosphatemia (Appendix B).
5.1.2.
Fulvestrant
Fulvestrant (Faslodex®) will be administered to patients in Cohort 4 only according to the 
approved commercial labeling.
Fulvestrant 500 mg will be administered IM into the buttocks (gluteal area), slowly (1 – 2 minutes 
per injection), as two 5-mL injections, one in each buttock, on Days 1 and 15 of Cycle 1, then 
Day 1 every subsequent cycle thereafter (every 28 days ± 3 days).  
Pre/peri-menopausal patients in Cohort 4 are required to also have ovarian suppression with 
goserelin as part of standard of care, having started a GnRH analogue at least 4 weeks prior to the 
first dose of fulvestrant.
5.1.3.
Treatment Duration
There is no predefined duration of treatment.  In all cohorts, study therapy may continue until 
disease progression, unacceptable toxicity, or any other criteria for treatment discontinuation is 
met (see Section 4.4).
5.2.
Definition of a Dose-Limiting Toxicity (Cohort 4 Only)
For patients in the safety lead-in portion of Cohort 4 only, a DLT is defined as any AE that is not
clearly attributable to an extraneous cause, such as an underlying disease, occurring in Cycle 1 and 
meeting at least one of the following criteria (Table 3). 

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Table 3:
Dose Limiting Toxicity Definition
Hematologic Toxicity
Grade 4 neutropenia lasting >7 consecutive days
Grade 4 thrombocytopenia lasting  >7 consecutive days
≥ Grade 3 thrombocytopenia with bleeding
Febrile neutropenia (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) requiring initiation of antibiotics
Hepatic Toxicitya
Grade 3 total bilirubin lasting >7 consecutive days
Grade 4 total bilirubin
Grade 3 AST and/or ALT lasting >7 consecutive days
Grade 4 ALT and/or AST lasting >3 consecutive days
For patients with liver metastases, AST or ALT >8 × ULN or AST or ALT 
>5 × ULN lasting ≥14 consecutive days 
Hy’s Law criteria - concurrent observation of the following, with no other 
reason found to explain the findings (such as viral hepatitis A, B, or C; 
preexisting or acute liver disease; or another drug capable of causing the 
observed liver injury):   
•
Elevated aminotransferase enzymes of >3 × ULN
•
Alkaline phosphatase (ALP) <2 × ULN
•
Associated with an increase in bilirubin ≥2 × ULN
Renal Toxicity
Creatinine clearance <30 mL/min for >3 days despite optimal supportive 
care
Other Non-Hematologic Toxicity
≥ Grade 3b
Other
Any toxicities leading to a TAS-120 Cycle 1 dose intensity of <75% and/or 
fulvestrant dose intensity of <100%
Inability to initiate Day 1 of Cycle 2 within 14 days of schedule due to any 
continuously ongoing Grade ≥ 2 toxicity 
Any death not clearly attributed to the underlying disease or extraneous 
causes
Abbreviations: ALP=alkaline phosphatase; ALT=alanine aminotransferase; ANC=absolute neutrophil count; AST=aspartate 
aminotransferase; ULN=upper limit of normal.
a.
For any Grade 3 or 4 hepatic toxicity not resolved within 7 days to Grade 0 – 1 (or Grade 2 if liver metastases), an 
abdominal computed tomography scan should be performed to assess if it is related to disease progression.
b.
The following events will not be considered DLTs: 

Nausea, vomiting and diarrhea (unless they persist to be Grade ≥3 for >3 consecutive days despite optimal 
supportive care)

Hyperphosphatemia (unless it persists to be Grade ≥3 for >7 consecutive days despite optimal phosphate-
lowering therapy)

Fatigue (unless it is lasting ≥1 week).

Asymptomatic Grade ≥3 electrolyte abnormality (unless it is lasting >72 hours). For patients with clinical 
symptoms, however, all Grade ≥3 electrolyte abnormalities regardless of duration will be considered a DLT.

Grade ≥3 amylase or lipase elevation not associated with symptoms or clinical manifestations of pancreatitis.

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5.3.
Dose and Schedule Modifications
5.3.1.
Dose and Schedule Modifications for TAS-120
5.3.1.1.
General Considerations
This section defines general dose modification guidelines for patients receiving TAS-120 in any 
cohort.  For detailed discussion of TAS-120 dose modification in Cohort 4 in the setting of a DLT, 
see Section 3.1.
In Cohort 4, in cases where a toxicity cannot be clearly attributed to either drug (TAS-120 or 
fulvestrant), TAS-120 should be modified or discontinued first.
The starting dose of TAS-120 is 

20 mg QD for all patients in Cohorts 1 – 3 

16 or 20 mg QD in Cohort 4, depending on the observations in the safety lead-in
(Section 3.1). 
Dose reduction to a minimum dose of 12 mg QD is permitted, with available dose levels of 16 mg 
QD and 12 mg QD. 
If dose reduction fails to result in achieving minimal criteria to resume treatment, or if toxicities 
occur which would necessitate reduction of the dose of TAS-120 below 12 mg QD, the patient 
should be discontinued from TAS-120. 
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 is required prior to the dose increase. 
If toxicities requiring dose reduction do not recover based on the criteria defined in Table 4
through Table 6 within 28 days after the last dose of TAS-120, the patient will be discontinued 
permanently from the study (Section 4.4). If resumption criteria are met within 28 days of the last 
dose of TAS-120, the patient may resume TAS-120 treatment at the appropriate dose level.
5.3.1.2.
Dose Modifications for Nonhematologic Toxicities
Dosing modification guidelines for nonhematologic toxicities are provided in Table 4. 
It is highly recommended to follow these guidelines, however, at the discretion of the Investigator, 
patients may continue on TAS-120 at the same dose without reduction or interruption for AEs 
(irrespective of grade) if the AE is considered unlikely to become serious or life threatening 
(including but not limited to fatigue and dry skin).  
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.

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Table 4:
TAS-120 Dosing Modification for Related Nonhematologic Toxicities
Grade
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 7
None
Grade 3
Hold treatment until return to baseline or 
Grade ≤1
Reduce by 1 dose level from the previous level, 
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 a dose hold or 
reduction.
Grade 4
Discontinue treatment 
Permanent discontinuation of TAS-120.
Grade 4 (lab 
abnormality
AE)
Hold treatment
TAS-120 will be permanently discontinued if 
assessed by the Investigator as life threatening.  If 
it is in the best interest of the patient to continue 
treatment in the opinion of the Investigator and 
after discussion with the Sponsor, the patient can 
continue treatment at a reduced dose level. 
However, TAS-120 should first be held until 
toxicity returns to baseline or Grade ≤1.
Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase.
Recommendations for hyperphosphatemia management are provided in Table 5. These are 
suggested guidelines based on emerging data from studies evaluating FGFR inhibitors, and from 
the experience of Investigators participating in ongoing studies of TAS-120. However, clinical 
judgment from treating physicians and local standard practices should be followed to decide the 
best management for each individual patient.

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Table 5:
Recommendations for Hyperphosphatemia Management
Serum Phosphorus Resulta
(mg/dL and mmol/L)b
Gradec
TAS-120 Dose Interruption and Modification
Recommended Phosphate Binder for 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 tablets 800 mg three times per day [TID].
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 (Fosrenol®) 
1.0 g QD or TID, and further titratione, 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 the serum phosphorus level has resolved to ≤ Grade 2 
within 14 days after dose reduction, continue TAS-120 at the 
reduced dose level. 

If the serum phosphorus level has not resolved to ≤Grade 2 
after 14 days, further reduce TAS-120 from the last reduced 
dose level (or no lower than 12 mg QD).

If the serum phosphorus level has not resolved to ≤ Grade 2 
after 14 days of the second dose reduction of TAS-120 (or no 
lower than 12 mg QD), interrupt dosing with 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 it’s 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 the serum phosphorus level has not 
resolved to ≤ Grade 2 after 14 days, permanently discontinue 
TAS-120.
Abbreviations: 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 if indicated.
b.
mmol/L = mg/dL × 0.3229 (conversion factor).
c.
This grading for the range of serum phosphorus levels will be used for the protocol.
d.
Phosphate binders 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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5.3.1.3.
Dose Modifications for Hematologic Toxicities
Criteria for dose interruption and resumption for hematologic toxicities are presented in Table 6.
Table 6:
TAS-120 Dose Interruption and Modification Criteria for Related 
Hematologic Toxicities
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 < 1000/mm3, 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; CTCAE=Common Terminology Criteria for Adverse Events; 
Hgb=hemoglobin; LLN=lower limit of normal; PLT=platelets.
5.3.1.4.
Adverse Event Follow-Up
All treatment-emergent AEs should be followed until resolution/stabilization or initiation of new 
anticancer therapy according to Table 7.

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Table 7:
Required Follow-up for Adverse Events
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 re-treatment 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×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, 
assessment of 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 × ULN 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 both baseline and abnormal electrocardiogram (ECG) finding to confirm 
the occurrence, severity, and causality of the AE. 
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. 
Nonlaboratory
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; ULN=upper limit of normal
5.3.2.
Dose and Schedule Modifications for Fulvestrant
The only dose modification for fulvestrant in the prescribing information (PI) is the 
recommendation for a reduction to 250 mg per IM injection for patients with moderate hepatic 
impairment (Child-Pugh Class B).  A Child-Pugh score of 7 – 9 is deemed Class B, and is a 
composite of scores for total bilirubin, serum albumin, prothrombin time, ascites and hepatic 
encephalopathy (Appendix C).
5.4.
Treatment Compliance
Each patient will be instructed to comply with the dosage and dosing regimen of TAS-120.  
Fulvestrant will be administered to patients in Cohort 4 only in the clinic under the supervision of 
clinic staff; all details of administration will be recorded in the eCRF.

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Compliance with all study medication administration should be documented in the patient’s source 
documents.
5.5.
Concomitant Medications and Therapies
The following therapies are permitted:

Bisphosphonates;

Denosumab;

Non enzyme-inducing anticonvulsants such as gabapentin, lamotrigine, and 
levetiracetam;

Steroids for patients with brain metastases; and/or

Local or regional palliative cryotherapy or radiation, such as for bone pain or palliative 
surgery (non-anti-neoplastic intent), provided this is not a site of measurable disease 
and is not indicative of disease progression. 
If, after assessment by the Investigator, radiation for brain metastasis, therapy for bone metastasis, 
or locoregional therapy should be initiated for the best benefit of the patient, the patient may begin
such therapy a minimum of 2 days after discontinuation of TAS-120. Consequently, the patient 
will be 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: may be administered as medically indicated (that is, blood transfusions, 
granulocyte colony-stimulating factor, erythropoietin stimulating agents) according to the 
institutional site standards or ASCO guidelines (Smith et al. 2015). 
Management of Diarrhea: Prophylactic treatment for diarrhea is permitted during the study if 
clinically indicated according to the institutional or published guidelines (Benson et al. 2004). 
Management of Nausea/Vomiting: Antiemetics may be administered as clinically indicated
according to institutional standards or ASCO guidelines (Hesketh et al. 2017).
5.5.1.
Drug Interactions
Drug interaction studies with TAS-120 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 D, Classification of Substrates, Inhibitors, and Inducers of CYP 
Enzymes and Transporters). 
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.

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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.
There are no known drug-drug interactions reported for fulvestrant (Fulvestrant PI).
5.5.2.
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.
Extended-field radiation therapy or palliative radiation to a focal site of measurable disease is also 
prohibited.  If it is deemed in the best interest of the patient and after discussion between the 
Investigator and Sponsor, it can be administered, but the patient will be censored for the primary 
endpoint analysis.
5.6.
Effective Contraception During Study
Female patients 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 study and for 90 days after the last dose of TAS-120 and 
1 year after last dose of fulvestrant (Cohort 4 only). Effective contraception is defined as follows:

Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation:
o
oral
o
intravaginal
o
transdermal

Progestogen-only hormonal contraception associated with inhibition of ovulation:
o
oral
o
injectable
o
implantable

Intrauterine device

Intrauterine hormone-releasing system

Bilateral tubal occlusion 

Vasectomized partner with documentation of the success of the vasectomy 

Complete abstinence from heterosexual intercourse (periodic abstinence is not a safe 
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Male patients with partners who are WOCBP should use a male condom in combination with at 
least one of the effective contraception methods for WOCBP during the study and for 90 days 
after the last dose of TAS-120 and 1 year after last dose of fulvestrant (Cohort 4 only).
Donation of sperm or ova is not allowed during the study and for 90 days following the last dose 
of TAS-120 and 1 year after last dose of fulvestrant (Cohort 4 only).
5.7.
Study Drug Materials and Management
TAS-120 will be supplied by the Sponsor; fulvestrant will be supplied by the Sponsor or procured 
by investigative sites. Detailed information, including requirements for accountability, and 
disposal of study drug will be provided in a separate Pharmacy Manual.
5.7.1.
Description of Study Drug
5.7.1.1.
TAS-120
A description of the TAS-120 study drug and packaging information are provided in Table 8.
Table 8:
TAS-120 Product Description and Packaging Information
Product Description and 
Dosage Form
Potency/
Strength
Appearance
Primary Packaging
TAS-120 Tablet
4 mg
Round, white, film-coated tablet
Aluminum/Aclar blister
5.7.1.2.
Fulvestrant
Please refer to the PI for the description of fulvestrant.
5.7.2.
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. Study drug name
e.
Tablet strength
f.
Lot number
g. Number of tablets in each container
h. Investigational caution statement
Additional clinical labeling will be added as required by local regulations.
Fulvestrant will follow the packaging and labeling specified on the PI and will receive additional 
clinical labeling as required by local regulations.

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5.7.3.
Study Drug Storage
TAS-120 tablets should be stored at room temperature (according to the country’s regulatory 
definition for room temperature) in accordance with the label.  
Fulvestrant should be stored per the storage conditions specified on the PI. All study medication 
must be kept in a locked area with access restricted to specific study personnel.
5.7.4.
Drug Accountability
The Investigator is responsible for ensuring that all TAS-120 received at the site is inventoried and 
accounted for throughout the study. TAS-120 will be stored and disposed of according to the 
Sponsor's instructions. The dispensing of TAS-120 to the patient and the return of TAS-120 from 
the patient must be documented in the patient’s source documents/the drug accountability form. 
Patients must be instructed to return all original containers, whether empty or containing study 
drug.  Dose reductions, interruptions, and reason for these actions must be recorded in the patient’s 
source documents and eCRF. 
The Investigator is responsible for ensuring that all fulvestrant received at the site is inventoried 
and accounted for throughout the study.  
At the conclusion of the study, all study drugs supplied by the Sponsor must be destroyed or 
returned to the designated depot, per the instructions provided in the Pharmacy Manual. 
TAS-120 is not to be used outside of this study.

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6.
STUDY ASSESSMENTS
6.1.
Study Assessments and Procedures
The Schedule of Events (Table 1) summarizes the frequency and timing of all applicable study 
assessments, including allowable windows for study visits and assessments / procedures. Written 
informed consent must be provided before any study-related procedures are performed.
6.1.1.
Determination of FGFR1 or FGFR2 Amplification Status
Determination of eligibility is based in part on the determination of FGFR1 or FGFR2
amplification status per the following methods:
6.1.1.1.
High-Level FGFR1 Amplification

The patient must have an FGFR1/CEN8 ratio of ≥5 or an FGFR1 copy number ≥10 signals 
per cell determined in tumor tissue using next-generation sequencing (NGS), fluorescence 
in situ hybridization (FISH), or other assays that can determine gene amplifications in 
tumor tissues.

May be based on local Clinical Laboratory Improvement Amendments (CLIA) or other 
similarly certified laboratory testing on tumor tissue using NGS, FISH, or another assay 
that can determine gene amplifications in tumor tissues.

Archival or (preferably) fresh tumor tissue must be available for central laboratory 
confirmation of FGFR1 amplification.
6.1.1.2.
FGFR2 amplification

May be based on local CLIA or other similarly-certified laboratory testing using NGS, 
FISH, or other assays that can determine gene amplifications in tumor tissues or circulating 
tumor DNA (ctDNA).

Archival or (preferably) fresh tumor tissue must be available for central laboratory 
confirmation of FGFR2 amplification.
6.1.2.
General Assessments
The following general assessments are performed as indicated in the Schedule of Events.

Demographics / medical history: Includes sex, age, race, clinical diagnosis, date and 
method of diagnosis, prior cancer therapy, and relevant medical history (past and 
concurrent).

Review eligibility criteria: Eligibility is assessed during the screening period and should 
be confirmed on Day 1 of Cycle 1, prior to first dose of study therapy.

Physical examination

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
Vital signs: Pulse rate, systolic and diastolic blood pressure, body temperature, and 
respiration rate. Any abnormal reading should be repeatedly immediately.

Height and body weight: Height is collected for the purpose of body mass index 
calculations at baseline only.

ECOG performance status: See Appendix A.

Pregnancy test: Serum β-human chorionic gonadotrophin (human chorionic stimulating
hormone) test required for WOCBP at screening and end of treatment; serum or urine test 
required at all other timepoints listed in the Schedule of Events.

Concomitant medication: Including all medications / therapies administered from the
time ICF is signed through 30 days after administration of the last dose of study therapy or
until the start of new anticancer therapy.

12-Lead electrocardiogram (ECG): Single, resting, semirecumbent 12-lead ECG will be 
performed locally. Data collection includes RR interval (heart rate), QT interval, QTcF
interval and abnormal findings; the Investigator is responsible for interpreting and 
measuring ECG data.
6.1.3.
Ophthalmological Examination
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 retina is visible through fundoscopy after dilation of the pupil. 
Ophthalmologic examination will be performed 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.  
Each evaluation will encompass: 
1. External ocular examination
2. Routine slit lamp biomicroscopy of anterior ocular structures, including the anterior and 
posterior chambers (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. Dilation of the pupil with direct/indirect fundoscopy per institutional guidelines and local 
clinical practice
6.1.4.
Laboratory Assessments
All laboratory assessments will be performed locally.  The laboratory must provide normal 
reference ranges for hematology, chemistry and coagulation tests. Laboratory results for 
hematology, chemistry, and coagulation assessments must be reviewed for clinically significant 
events. Any clinically significant events must be followed and reported as required by the protocol 
(see Section 8.4.1).

Hematology assessments include: Red blood cell count, hemoglobin, hematocrit, platelets, 
white blood cell count with differential (ANC, lymphocytes, monocytes, eosinophils, 
basophils)

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
Coagulation assessments include: Prothrombin time-international normalized ratio, 
activated partial thromboplastin time, fibrinogen

Chemistry (serum or plasma) assessments include: AST, ALT, alkaline phosphatase 
(ALP), total bilirubin, direct bilirubin, albumin, lactate dehydrogenase, inorganic 
phosphorus, triglyceride, total cholesterol, creatinine, urea or blood urea nitrogen, sodium, 
potassium, chloride, calcium, magnesium, blood glucose, creatinine clearance (if there is a 
measured value, use the measured value) or estimated glomerular filtration rate.
For a calculated creatinine clearance (Ccr) value, use the Cockcroft-Gault formula:
Male Ccr (mL/min) = Body wt (kg)×(140-age)[72×serum creatinine (mg/dL)]
Female Ccr (mL/min) = male Ccr×0.85
6.1.5.
Tumor Assessments/Scans
On-site tumor assessments (including computed tomography [CT]/magnetic resonance imaging 
[MRI]) will be performed by the Investigator/local radiologist according to RECIST 1.1 guidelines 
(Eisenhauer et al. 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 
study therapy. Response definitions are provided in Section 7.2.1. 
If the Investigator determines that a patient has developed clinical disease progression manifested 
by symptomatic deterioration but not supported by radiologic evidence of progression, the patient 
may stop treatment. Symptoms of clinical disease progression must be documented in the patient’s 
source documents and must be reported as AEs. Every effort should be made to document 
objective disease 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. 
Please see Section 7 for more detailed discussion of efficacy evaluations.
Note that patients who discontinue without documented disease progression should continue to 
undergo tumor assessments/scans according to the Schedule of Events until PD is documented, 
new anticancer therapy is initiated, the study is terminated, or consent is withdrawn.
6.1.6.
Safety Evaluations
For a detailed description of safety data collection, please refer to Section 8.
6.1.7.
Pharmacodynamic Evaluations
For discussion of pharmacodynamic evaluations planned in this study, including collection of 
blood samples for ctDNA assessment and optional fresh tumor biopsies, please refer to Section 9.
6.1.8.
Pharmacokinetic Evaluations
For discussion of PK evaluations planned in this study, including collection of blood samples, 
please refer to Section 9.

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6.1.9.
Survival Follow-Up
Please refer to Section 3.2.6.

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7.
EFFICACY EVALUATIONS
7.1.
Efficacy Criteria
The determination of antitumor efficacy will be based on the results of objective tumor 
assessments/scans interpreted by the Investigator, according to RECIST 1.1.
7.1.1.
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 each assessment timepoint. 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 
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 (eg, 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 (eg, 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 RECIST 1.1 specifications for standard anatomical radiological 
imaging.
7.1.2.
Tumor Definitions
Measurable Lesions: Only measurable lesions can be selected as target 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 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.

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Non-measurable Lesions: All non-measurable lesions can only be selected as non-target lesions.

Small visceral metastatic lesions that have a longest dimension <10 mm, or if slice 
thickness is >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 (eg, ascites and peritoneal carcinomatosis)
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 (ie, visceral lesion) target lesions. Therefore, in cases of 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 timepoint.

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. 

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 cannot be read due 
to technical reasons including:

CT artifact

Patient positioning where the lesions are obstructed or cannot be seen

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.” 

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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 <1 mm are considered non-pathological and should not 
be recorded. 

Any equivocal lesion without clear diagnosis (eg, 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 (eg, multiple enlarged pelvic lymph nodes or multiple liver metastases).
7.2.
Efficacy Endpoints
The efficacy evaluation criteria described in Section 7.1 will be used to derive the following 
primary and secondary efficacy endpoints (Table 9). Definitions of each endpoint are provided in 
Section Section 10.5.2.
Table 9:
Efficacy Endpoints
Primary
Secondary
ORR (Cohorts 1 and 2)
CR rate (Cohort 3); ORR (Cohort 4)
CBR (Cohort 3)
DOR (All)
6-month PFS (Cohort 4)
CBR (Cohorts 1, 2, and 4)
PFS (All)
6-month PFS (Cohorts 1, 2, and 3)
OS (All)
Abbreviations: CBR=clinical benefit rate; DOR=duration of response; ORR=objective response rate; 
OS=overall survival; PFS=progression-free survival
7.2.1.
Response Criteria
Efficacy evaluation will include the assessment of target and non-target tumor responses as well as 
objective responses. Responses will be assessed as defined in the statistical analysis plan (SAP).

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7.2.1.1.
Target and Non-Target Response Assessments
Assessments will be based on the definitions for target and non-target lesions described in 
Table 10.
Table 10:
Target and Non-target Lesions
TARGET LESIONS
Lesions Response:
Definition:
Complete Response (CR)
Disappearance of all target lesions. Any pathological lymph node 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, referencing the smallest sum diameters while on study.
NON-TARGET LESIONS
Lesions 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)
Partial Response (PR)
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 following 
definition).
Abbreviations: CR=complete response; PD=progressive disease; PR=partial response; SD=stable disease
Progression in Non-target Disease: There must be an overall level of substantial worsening in 
non-target disease such that, even in the presence of SD or PR in target disease, the overall tumor 
burden has increased sufficiently to merit discontinuation of therapy.
7.2.1.1.1. Additional Criteria to Consider When Making Tumor Response Assessments 
Because worsening in non-target disease cannot be easily quantified, a useful test that can be 
applied when assessing patients for unequivocal progression is to consider if the increase in 
overall disease burden based on the change in non-measurable disease is comparable in magnitude 
to the increase that would be required to declare PD for measurable disease (ie, an increase in 
tumor burden representing an additional 73% increase in “volume” [which is equivalent to a 20% 
increase in the diameter of a measurable lesion]). 
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 
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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 (eg, 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.
7.2.1.2.
Objective Response Assessment
Assessments will be based on the definitions provided in Table 11 and Table 12.
Since this is a non-randomized study, all responses (CR/PR) must be confirmed.
Table 11:
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
NE
PD
Any 
Yes or No 
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
Abbreviations: CR=complete response; NE=not evaluable; PD=progressive disease; PR=partial response; 
SD=stable disease
Table 12:
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 
NE
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
Abbreviations: CR=complete response; NE=not evaluable; PD=progressive disease; PR=partial response; 
SD=stable disease

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8.
SAFETY INFORMATION
8.1.
Adverse Events
8.1.1.
Definitions of Adverse Events
An AE is any untoward medical occurrence in a clinical study patient and does not necessarily 
have a causal relationship with the study drug. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal finding), symptom, or disease temporally associated with 
the use of a study drug, whether or not related to the study drug. This includes any occurrence that 
is new in onset or aggravated in severity or frequency from the baseline condition, or abnormal 
results of diagnostic procedures, including laboratory test abnormalities.
All AEs will be collected from the time the main ICF is signed through 30 days after the last dose 
of study therapy (safety follow-up) or until the start of new antitumor therapy, whichever is earlier.
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. Any untoward medical event that occurs after the safety follow-up is 
not considered an AE, unless the Investigator considers that the AE is related to the study drug. 
Serious AEs related to study therapy will be collected through the survival follow-up.
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.
Signs and symptoms of a pre-existing disease should not be considered an AE, but should rather 
be considered baseline signs and symptoms. Worsening of pre-existing signs and symptoms is
considered an AE.
For definitions and reporting of pregnancies, overdoses, and medication errors, refer to 
Section 8.5.1, Section 8.5.2, and Section 8.5.3, respectively.
8.1.2.
Reporting of Adverse Events
8.1.2.1.
Terms of Reported Adverse Events
All AEs will be documented in the eCRF according to the eCRF Completion Guidelines. 
When a diagnosis for the reported signs or symptoms is known, the Investigator should report the 
diagnosis, not the symptoms, as the AE.
Adverse events can be spontaneously reported or elicited during open-ended questioning, 
examination, or evaluation of a patient in order to prevent reporting bias, patients should not be 
questioned regarding the specific occurrence of 1 or more AEs.
8.1.2.2.
Severity of Adverse Events
The NCI-CTCAE Version 5.0 will be used to grade the severity of AEs.

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8.1.2.3.
Causal Relationship with Study Drug
The causal relationship between an AE and study drug will be assessed using the following 
2-point scale, taking into account the patient’s condition, medical history, concomitant 
medications, and the temporal relationship between study drug administration and onset of the 
event.
1.
An AE is considered to be “Related” if the event follows a reasonable temporal sequence 
from administration of study drug and there is a reasonable possibility that 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.

A single occurrence of an event that is uncommon and known to be strongly associated 
with drug exposure (eg, angioedema, Stevens-Johnson syndrome).
2.
An AE is considered to be “Not related” if there is no reasonable possibility that:

The event occurred prior to study drug administration.

There is no reasonable possibility that the study drug caused the event. 

The event does not follow a reasonable temporal sequence from administration of study 
drug 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 study drug and the AE.
8.1.2.4.
Outcome of Adverse Events
Record the outcome of AEs as follows:
1.
Resolved
2.
Not resolved
3.
Fatal
The AE reporting process is provided in the eCRF Completion Guidelines.
8.1.2.5.
Follow-up of Adverse Events
Any ongoing AEs should be followed until the earliest occurrence of one of the following:

The AE has resolved or stabilized

Completion of Safety Follow-up visit

Start of new antitumor therapy

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
Withdrawal of consent

Death

Other (eg, transfer to another hospital)
8.2.
Serious Adverse Events
8.2.1.
Definitions of Serious Adverse Events
An SAE is any untoward medical occurrence that at any dose:

Results in death

Is life-threatening
o
The term "life-threatening" in the definition of "serious" refers to an event in which 
the patient was at risk of death at the time of the event; it does not refer to an event 
which hypothetically might have caused death if it were more severe.

Requires inpatient hospitalization or prolongation of existing hospitalization to treat the 
AE
o
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.

Results in persistent or significant disability/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.

Is a congenital anomaly/birth defect (if exposure to product just before conception or 
during pregnancy resulted in an adverse outcome in the child).

Is any other important medical event that based upon appropriate medical judgement may 
jeopardize the patient or may require medical or surgical intervention to prevent one of the 
other outcomes listed in the definitions above. (eg, may not result in death, be 
life-threatening, or require hospitalization). 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, or development of 
drug dependency or drug abuse.
8.2.2.
Reporting of Serious Adverse Events (within 24 hours)
SAEs must be reported to the Sponsor’s Pharmacovigilance group or its designee within 24 hours
from the time the Investigator first becomes aware of the SAE. 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 

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serious criterion. The SAE reporting process and contact information are provided on the paper 
SAE Form Completion Guidelines.
All SAEs occurring from the time the ICF is signed through the Safety Follow-up Period (30 days 
after the last dose of study drug or discontinuation, whichever is earlier) must be reported to the 
Sponsor’s Pharmacovigilance group or its designee. Any untoward medical event that occurs after 
the Safety Follow-up Period or discontinuation (whichever is earlier) is not considered an SAE, 
unless the Investigator considerers that the SAE is related to the study drug.
After the initial SAE notification to the Sponsor’s Pharmacovigilance group or its designee, all 
follow-up SAE information will be submitted each time they become available (for example, 
clinical diagnosis, outcome, causality assessment, results of specific investigations) on a follow-up 
paper SAE form.
The Investigator also must submit further information if it is required by the Sponsor, the director 
of the study site, or an institutional review board (IRB)/independent ethics committee (IEC).
8.2.3.
Reporting of Deaths
All deaths, including death due to disease progression, occurring from the time the ICF is signed 
through the Safety Follow-up Period (30 days after the last dose of study drug or discontinuation, 
whichever is earlier) must be reported as an SAE on a paper SAE form within 24 hours from the 
time the Investigator first becomes aware of the death.
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 
for cause of death:

Toxicity caused by study drug

Disease progression

Clinical disease progression

Other causes
8.2.4.
Follow-up of Serious Adverse Events
When an SAE occurs, the Investigator will promptly take appropriate measures and follow up with 
the patient until the earliest occurrence of one of the following:

The SAE has resolved

The SAE has stabilized; an SAE can only be considered “stabilized” if the clinical 
manifestation or laboratory results being followed/assessed has remained constant (is not 
worsening) based on the Investigator's medical judgement.

Start of new antitumor therapy

Death

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8.3.
Disease Progression
Disease progression is not an acceptable AE term. In cases of non-fatal disease progression, the 
relevant symptom(s), sign(s), and complication(s) that led to the diagnosis of clinical disease 
progression should be reported as AE(s). If the relevant symptom(s), sign(s), and complication(s) 
meet any of the serious criteria, they should be reported as SAE(s).  In both cases it should be 
indicated whether the symptom(s), sign(s), and complication(s) are related to clinical disease 
progression. 
In cases of death due to clinical disease progression, the relevant major symptom(s), sign(s), and 
complication(s) that led to the death should be reported as SAE term(s). Clinical disease 
progression may only be reported as an SAE term if none of the relevant symptoms, signs, or 
complications supports a fatal outcome.
8.4.
Laboratory Assessments
8.4.1.
Reporting and Evaluation of Laboratory Test Results
All laboratory results must be reviewed by the Investigator. A new laboratory or instrumental 
abnormality that has a clinical impact on a patient (including eg, resulting in study drug dose 
reduction, treatment delay, treatment discontinuation or requirement of intervention) is considered 
an AE, unless it is considered part of clinical manifestations to a clinical diagnosis that is already 
reported as an AE.
All laboratory values that are out of the normal range are to be evaluated for their clinical impact
before exposing the patient to the next dose of TAS-120. The laboratory must provide normal 
reference ranges.
The NCI-CTCAE Version 5.0 will be used to grade the severity of laboratory data.
8.4.2.
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 another treatment is 
given.
8.5.
Other Safety Information
8.5.1.
Pregnancy
If a patient becomes pregnant while on study treatment or within 30 days following the last dose 
of study therapy, the study treatment must be immediately discontinued if ongoing. Pregnancy 
information in a female patient (or for 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 paper Pregnancy Form and faxing or e-mailing it to 
Sponsor’s Pharmacovigilance group or its designee.
New and/or corrected information regarding the pregnancy obtained after submitting the 
Pregnancy Form must be submitted on an updated Pregnancy Form to the Sponsor’s
Pharmacovigilance group or its designee.

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If the outcome of the pregnancy is a stillbirth, congenital anomaly/birth defect, or a serious event 
in the mother, it should be reported as a SAE to the Sponsor’s Pharmacovigilance group or its 
designee. Live births will be followed up by the Investigator. Any information that may be 
associated with the study drug should be reported even after study completion.
8.5.2.
Overdose
An overdose for this clinical study is defined as taking an intentional or unintentional dose of 
TAS-120 or fulvestrant beyond the recommended dose for 1 day or beyond the recommended total 
dose in each cycle.
An overdose of TAS-120 or fulvestrant should be reported as an AE, and must be recorded on the 
SAE form and/or eCRF (or other specified report form) and reported to the Sponsor’s 
Pharmacovigilance group or its 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). 
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 or fulvestrant overdose. Overdose should 
be managed with close monitoring and administration of prophylactic and symptomatic therapies 
to prevent or correct potential side effects.
8.5.3.
Medication Errors
A medication error for this clinical study is defined as any unintentional error in prescribing, 
dispensing, or administering the study drug while the study drug is in the control of the healthcare 
professional or patient.
Please refer to the current eCRF Completion Guidelines for the details regarding reporting of 
medication errors to the Sponsor’s Pharmacovigilance or designee.
The following types of medication errors, regardless of whether it is associated with an AE or 
SAE, should be reported to the Sponsor’s Pharmacovigilance or designee within 24 hours of first 
awareness from the time the Investigator first becomes aware of its occurrence, using the SAE 
form and/or eCRF (or other specified report form):

Medication errors with study medication or concomitant medication resulting in an AE

Medication errors with study medication resulting in an overdose

Incorrect route of study medication administration

Administration of the incorrect study medication
Note: 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 a SAE, but will be identified through the recording of 
study drug accountability data in the eCRFs.

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9.
PHARMACODYNAMIC AND PHARMACOKINETIC 
EVALUATION
9.1.
Pharmacodynamic and Biomarker Assessments
9.1.1.
Objectives and Background
Exploratory objectives of this study are to assess the downstream pharmacodynamic effect of 
TAS-120 in single-agent and/or combination therapy and to explore markers of response and 
mechanisms of resistance to TAS-120 in tumor tissue biopsies and/or in ctDNA. These 
exploratory assessments of biomarkers include but are not limited to:

Any FGFR aberrations

p-AKT

p-MAPK

Ki67
All biomarker assessments described in this section will be performed at the timepoints shown in 
the Schedule of Events (Table 1); methods of sample collection and preparation will be described 
in a separate Laboratory Manual.
The pharmacodynamic biomarker population will consist of all patients who received TAS-120
and have evaluable pharmacodynamic biomarker data. Detailed analytical procedures will be 
described in the SAP.
9.1.2.
Assessment of FGF/FGFR Aberrations in Blood
A blood sample will be collected to assess FGF/FGFR aberrations in ctDNA prior to the first 
TAS-120 administration on Day 1 of Cycle 1, on Day 1 of each alternative uneven cycle (Cycle 3, 
5, 7 and ongoing), at time of disease progression, and at the EOT visit. 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.
9.1.3.
Tumor Biopsy
Archival or fresh tumor biopsy samples will be collected during the screening period to 
retrospectively confirm FGFR gene status at the Sponsor’s designated central laboratories. The 
remaining samples may be stored at the Sponsor’s designated central laboratories for up to 
10 years for future testing.
Optional pre- and post-treatment tumor biopsies for pharmacodynamic assessment will be 
collected from patients who consent at Baseline, at the end of Cycle 1 (Cycle 1 Day 28 ± 7 days), 
and at the time of disease progression. These samples are being collected for exploratory analysis 
to evaluate the changes of downstream protein activation and other markers that may be associated 
with response and/or development of resistance to TAS-120 in tumor tissues. 

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9.2.
Population Pharmacokinetic Sample Collection and Analysis
Blood samples will be collected for PopPK analysis including estimation of steady-state exposure 
such as AUC. The samples will be used to determine concentrations of TAS-120 in plasma. 
Total of three PK samples will be collected on Cycle 2, Day 1 (C2D1), within 1 hour prior to 
dosing and at 2 hours (±1 hour) and 5 hours (at least 3 hours apart from sampling at 2 hours) post-
dose.  The 3 samples should be collected on the same day. A pre-dose sample may be collected 
again in case the patient interrupted medication after the pre-dose sample was collected and had 
C2D1 at a later date. The second pre-dose sample will be recorded as pre-dose sample for C2D1.  
Dates and times of each sample collection must be recorded.
Details on the collection and preparation of plasma samples will be provided in a separate 
Laboratory Manual.  Detailed analytical procedures will be described in the independent SAP for 
PopPK.

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10.
STATISTICS
The statistical analysis methods will be documented in detail in the SAP.
10.1.
Estimation of Sample Size
Up to 168 patients in total may be enrolled in the study. 
Please note: the patient numbers given for efficacy analysis are for the response-evaluable 
population, defined as the subset of treated patients who have measurable disease (or evaluable 
disease in Cohort 3), who have at least 1 post-baseline disease/tumor assessment, and who have 
centrally confirmed FGFR amplification (Table 13).  If a treated patient is not eligible for the 
response-evaluable population (for example, because FGFR amplification cannot be centrally 
confirmed or no post-baseline tumor assessment is available), additional patients will be enrolled 
to ensure the correct number of response-evaluable patients for analysis as described below.
Sample size considerations for Cohorts 1 and 2 (primary endpoint ORR) are based on a 2-stage 
Optimal Simon design, comparing a poor response of ≤15% versus a promising response of ≥30%, 
at an approximate 5% 1-sided significance level and 80% power.

In Stage 1 (futility assessment), enrollment will include 19 patients in each cohort and 
accrual will continue to Stage 2, if at least 4 (21%) of 19 patients respond (CR or PR). 

In Stage 2, if the Stage 1 futility boundary is exceeded, an additional 36 patients will be 
enrolled, for a total of at least 55 patients per cohort.  In Cohorts 1 or 2, with a total of 
55 patients, if the observed ORR is 30.9%, the 95% exact confidence interval (CI) is 
(19.1%, 44.8%).
Sample size considerations for Cohort 3 (primary endpoint CBR) are also based on a 2-stage 
Optimal Simon design. The null hypothesis that the true CBR is 25% will be tested against a 
1-sided alternative, which yields a type I error rate of 5% and power of 80% when the true CBR 
rate is 50%. In the first stage, 9 patients will be treated. If there are ≤2 patients with clinical benefit 
(ie, CR or SD ≥24 weeks) in these 9 patients, the cohort will be discontinued. Otherwise, 
15 additional patients will be treated for a total of 24 patients. The null hypothesis will be rejected 
if ≥11 patients with clinical benefit are observed in 24 patients. 
Sample size considerations for Cohort 4 (primary endpoint 6-month PFS) are based on a 
proof-of-concept Phase 2 design, differentiating a null 6-month 25% PFS rate with a target rate of 
50%. Approximately 28 patients will be treated. It has approximately 80% power to reject the null 
hypothesis that the true 6-month PFS rate is ≤25%, considering a 1-sided alpha (type 1 error rate) 
of 5%. In addition, 6-12 patients will be enrolled as a safety lead-in. The patients in the safety 
lead-in who are treated at the recommended Phase 2 dose will be included in the main cohort of 
28 patients. Thus up to 34 patients may be enrolled for this cohort.
10.2.
Planned Interim Analysis
The Sponsor will review the data at the time a cohort has the required number of patients to 
determine if that particular cohort should continue. 

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10.3.
Analysis Populations
The analysis study populations in this study are defined in Table 13.
Table 13:
Analysis Populations
Analysis Population
Definition
All Enrolled Population:
All patients enrolled in this study
All Treated Population/Full 
Analysis Set:
All enrolled patients who received at least 1 dose of study drug
DLT Evaluable Set:
All patients in the All Treated Population in Cohort 4, excluding those 
for whom the cumulative dose of TAS-120 was <75% and/or the 
cumulative dose of fulvestrant was <100% for reasons other than DLTs 
in Cycle 1, or who received prohibited concomitant medications or 
therapies
Response Evaluable Set:
All patients in the All Treated Population who meet Inclusion Criterion 
#4, have measurable disease (or evaluable disease in Cohort 3), who 
have at least 1 post-baseline disease/tumor assessment, and have 
centrally confirmed FGFR amplification. Patients who discontinue due 
to intolerable toxicity or death prior to the first post-baseline tumor 
assessment will also be considered evaluable and will be classified as 
non-responders.
PopPK Evaluable Set:
All patients in the All Treated Population who have evaluable plasma 
TAS-120 concentration data for analyses
Pharmacodynamic/Biomarker 
Evaluable Set:
All patients in the All Treated Population who have evaluable 
pharmacodynamic/biomarker data for analyses
Abbreviations: DLT=dose-limiting toxicity.
10.4.
Criteria for Handling of Patient Data
Criteria for handling of patient data in the study are provided in the SAP.

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10.5.
Statistical Analyses
10.5.1.
Demographic and Baseline Characteristics
The number of patients in each study population and the reasons for exclusion will be 
summarized. In each analysis population, the distribution of main patient background, disease 
characteristics, and baseline laboratory values and clinical findings will be summarized. These 
patient attributes will be summarized using frequency distribution or descriptive statistics as 
appropriate.
10.5.2.
Efficacy Analyses
A description of each efficacy endpoint is provided in Table 14. Tumor assessments will be 
performed as per Section 6.1.5. Response assessments will be made based on RECIST 1.1. See the
SAP for more detailed information on the efficacy analyses.
The evaluation of endpoints will be based on Investigator assessment and central independent 
radiology review.
Table 14:
Efficacy Endpoint Definitions
Endpoint
Definition
ORR
The percentage of patients with a confirmed response of 
either CR or PR
CBR
The percentage of patients with a confirmed response of PR 
or CR or SD lasting at least 24 weeks (Cohorts 1, 2 and 4)
The percentage of patients with a confirmed response of CR 
or SD lasting at least 24 weeks (Cohort 3)
PFS
The time from the day of first dose to the date of first 
objectively documented disease progression or death (any 
cause), whichever occurs first
6-month PFS
The percentage of patients who remain alive and progression 
free at 6 months
DOR
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
OS
The time from the date of first dose to the death date
Abbreviations: CBR=clinical benefit rate; CR=complete response; DOR=duration of response; 
ORR=objective response rate; OS=overall survival; PFS=progression-free survival; PR=partial 
response; SD=stable disease.
Efficacy data for the primary and secondary endpoints will be summarized descriptively. 
The primary endpoint of ORR will be determined for patients in the Response Evaluable Set. 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.

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Duration of response will only be evaluated in patients with objective response of CR or PR.
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 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.
Progression-free survival will be estimated using the Kaplan-Meier method. 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.
Overall survival will be analyzed similar to PFS. 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 known 
alive date.
10.5.3.
Safety Analyses
The safety analysis will be performed using the All-Treated Population.
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
terminology and the severity of the toxicities will be graded according to the NCI-CTCAE 
(Version 5.0), where applicable. 
Concomitant medications will be coded according to the World Health Organization Drug 
Dictionary for Concomitant Medication.
All AEs will be summarized (by incidence) and listed by the System Organ Class, Preferred Term, 
toxicity/severity grade, and causal relationship to TAS-120. In addition, separate summaries of 
SAEs and Grade 3 or 4 AEs will be presented.
For all AEs that occurred between the signing of the ICF and the last day of the Safety Follow-up 
Period, lists of preferred AE terms, grade, onset date, actions, outcome of AE, date of outcome 
confirmed, causalities with the study drug, and comments on AEs will be listed by patient.
Hematological and chemistry laboratory parameters will be graded according to the NCI-CTCAE 
(Version 5.0) 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.
Safety data (AEs and clinical laboratory results) will be summarized descriptively. A list of 
12-lead ECG findings will be presented by patient.
10.5.4.
Pharmacokinetic Analysis
PopPK is described in Section 9.2. Analyses will include all patients in the All Treated Population
who have evaluable plasma TAS-120 concentration data for PK analyses, unless any key 
information such as dosing records was missed. The data will be integrated with other studies and 
analyzed by the nonlinear mixed effect modeling. Individual PK parameters will be estimated for 

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the subsequent exposure-response analysis if the estimation is feasible. The results will be 
summarized and reported separately.
10.5.5.
Pharmacodynamic/Biomarker Analysis
The exploratory pharmacodynamic/biomarker endpoints are described in Section 9.1. Analyses 
will be performed using all patients in the All Treated Population who have evaluable data for 
pharmacodynamic/biomarker analyses.
Pharmacodynamic and biomarker data will be summarized descriptively.

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11.
ADMINISTRATIVE CONSIDERATIONS
11.1.
Protocol Compliance
The Investigator will agree to comply with the protocol by signing the Declaration of Investigator.
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 notice is 
requested). The new Investigator must accept the responsibility in writing and be approved by the 
Sponsor and the IRB/IEC.
11.2.
Protocol Deviations
The Investigator may implement a deviation from, or a change in, the protocol to eliminate an 
immediate hazard(s) to study patients without prior IRB/IEC approval/favorable opinion. As soon 
as possible, the implemented deviation or change and the reasons for it should be documented and 
submitted to the IRB/IEC and Sponsor.
The Investigator is to record any deviation from the protocol in the source documents, describing 
this departure and the circumstances under which it was required.
11.3.
Protocol Amendments
All protocol amendments must be issued by the Sponsor, and signed and dated by the Investigator. 
Documentation of amendment approval by the Investigator and IRB/IEC must be provided to the 
Sponsor.
If the changes involve only logistic or administrative aspects of the study, these changes will be 
notified in writing by the Sponsor.
11.4.
Study Termination
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 or discretionary reasons 
at any time.
In this case, the Sponsor will promptly notify study site personnel with the reasons for study 
termination.  Study site personnel will promptly inform the IRB/IEC and the Investigator in 
writing.  The Investigator will immediately advise the patients of the termination of the study and 
discuss other healthcare options with the patient.  The Sponsor will promptly notify the Regulatory 
Authorities of the premature termination of the study.
11.5.
Post-trial Provisions
Please see Section 3.3 for discussion of Study Completion and Study Extension.

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11.6.
Case Report Forms
The Investigator should complete all eCRFs in accordance with the eCRF Completion Guidelines. 
Data in the eCRFs shall be consistent with source documents.
In this study, the Investigator and assigned personnel will be given access to the electronic data 
capture (EDC) system; passwords should not be shared. Data managers and Monitors will have the 
right to access the EDC system for performing source data verification. Data managers will have 
the right to access the EDC system as appropriate for their roles. Other relevant personnel may 
receive access to view EDC data.
An eCRF should be completed for each screened and enrolled patient.
After verification of the eCRFs, the Sponsor or designee may query discrepancies or request 
additional information. The Investigator, or assigned personnel, should verify the data and correct 
as necessary prior to approval of the eCRFs.
11.7.
Access to Source Data/Documents
The Investigator or designated study personnel must make all study-related records available for 
study-related monitoring, audit, IRB/IEC review, and regulatory inspection.
11.7.1.
Source Data/Documents
Source documents are original documents, data, and records such as hospital records, clinical and 
office charts, laboratory notes, memoranda, patient’s evaluation checklists, pharmacy dispensing 
records, recorded data from automated instruments, microfilm or magnetic media, X-ray, patient 
files, and records kept at the pharmacy, laboratories, and medical-technical departments involved 
in the study.
Specific details regarding source documents and source data to be recorded directly on the eCRFs 
for the study should be identified with the Investigator prior to and during the study.
11.7.2.
Source Data Verification
The Sponsor’s study monitor, or other representatives, should verify the entries in the eCRF and 
source documents to confirm the completeness and accuracy of the data. If there are any 
discrepancies between the entries in eCRFs and source documents, the monitor will query the site.
11.8.
Data Handling
All study information is confidential. The patient’s 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 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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11.9.
Responsibilities of Recordkeeping
11.9.1.
Investigator and Study Site
The Investigator and the study site are responsible for the retention of all study documents 
according to institutional policies, local laws, and International Council for Harmonisation (ICH)
E6 Guideline.
The Investigator and the study site agree to inform the Sponsor in writing of the intention to 
remove or destroy any study-related records. Prior to contacting the Sponsor, the Investigator and 
study site must ensure that the applicable regulatory requirements have been satisfied. The 
Sponsor will evaluate the requests from the Investigator and the study site and will provide 
authorization for destruction of such records in writing.
In the event that all retention of records requirements have been fulfilled, but the Sponsor requests 
that the Investigator and study site maintain the records for a longer period of time, additional 
arrangements will be made.
11.9.2.
Sponsor
The Sponsor must retain all Sponsor-specific essential documents in conformance with the 
applicable regulatory requirements of the countries where the product is approved, and where the 
Sponsor intends to apply for approvals.
If the Sponsor discontinues the clinical development of the study drug, the Sponsor must maintain 
all Sponsor-specific essential documents in conformance with the applicable regulatory 
requirements.
11.10.
Monitoring
The Sponsor and designee will be allowed to conduct site visits to the investigation facilities for 
the purpose of monitoring any aspect of the study. The Investigator agrees to allow the monitor to 
inspect the drug storage area, study drug stocks, drug accountability records, patient charts and 
study source documents, and other records relative to study conduct.
11.11.
Financial Disclosure
Financial disclosure for Investigators will be obtained and record keeping of financial records will 
be in accordance with local regulatory requirements. Investigators will provide the Sponsor with 
sufficient, accurate financial information upon the Sponsor’s request.
11.12.
Compensation for Health Injury
The clinical study is insured according to applicable regulatory requirements. A copy of the 
Compensation Policy Document will be provided to the study site by the Sponsor. In the case of a 
compensation claim, excluding claims that have arisen due to medical malpractice or negligence, 
the legally responsible person is clearly identified. Sponsor should address the policies and 
payment procedures of compensation for the event of study-related injuries as the Compensation 
Policy Document. When patients receive compensation, the policies and payment procedure of 
compensation should comply with the Compensation Policy Document.

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12.
QUALITY CONTROL AND QUALITY ASSURANCE
The Sponsor will perform quality control and quality assurance procedures in accordance with the 
Sponsor's SOPs to ensure the quality of the clinical study.
12.1.
Quality Control
The Sponsor is responsible for controlling the quality of the clinical study according to the SOPs 
regarding eg, study operation, monitoring, data collection and management, statistical analysis,
and handling of safety information to verify that the study-related activities have been fulfilled.
12.2.
Quality Assurance
To ensure compliance with Good Clinical Practice (GCP) and all applicable regulatory 
requirements, the Sponsor may conduct a quality assurance audit. Authorized representatives of 
the Sponsor, a Regulatory Authority, or an IRB/IEC may visit the site to perform audits or 
inspections, including source data verification. 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 study.
The purpose of an audit or inspection is to systematically and independently examine all 
study-related activities and documents to ensure that these activities were conducted, and data 
were recorded, analyzed, and accurately reported according to the protocol, ICH GCP E6 
guidelines, and any applicable local regulatory requirements. The Investigator should contact the 
Sponsor immediately if contacted by a Regulatory Agency regarding an inspection.
Any results arising from such inspections will be immediately communicated by the Investigator 
to the Sponsor. The Investigator and the Sponsor will take corrective actions for all findings and 
observations found during audits and/or inspections. The auditors and inspectors will not disclose 
private information unless required by law.

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13.
ETHICS
13.1.
Ethical Conduct of the Study
It is mandatory that all considerations regarding the protection of patients be carried out in 
accordance with the latest versions of the protocol, ICH GCP Guidelines, the ethical principles 
that have their origin in the Declaration of Helsinki, and all applicable regulatory requirements.
13.2.
Written Informed Consent
The ICF must be approved by the IRB/IEC before patients sign consent for any study-related 
activity. It must be in a language that the patient can read and understand. The process for 
obtaining consent should be in accordance with principles that originated in the Declaration of 
Helsinki, current ICH and GCP guidelines, and applicable regulatory requirements. Each patient 
(or a legally acceptable representative) must give written consent according to local requirements. 
The Investigator(s) must maintain the original, signed ICF. A copy of the signed ICF must be 
given to the patient.
There must be documentation in each patient’s case history/medical record that informed consent 
was obtained prior to any study procedure being performed. Patients must be re-consented to the 
most current version of the ICF(s) throughout their participation in the study (including during 
survival follow-up).
13.3.
Institutional Review Board/Independent Ethics Committee
The study must be approved by an appropriately constituted IRB/IEC, as required in the applicable 
local regulation such as ICH E6 Guidelines (Part 3), Code of Federal Regulations Title 21, part 56, 
and Ordinance of the Ministry of Health and Welfare No. 28, Chapter IV, Section 1 before the 
study is initiated. At the end of the study, the Investigator will notify the IRB/IEC of the
conclusion of the study and its outcome.

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14.
PUBLICATION POLICY
14.1.
Publication Policy
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 or region.
The results of the study may be presented during scientific symposia and/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.
The Investigators and the Sponsor will discuss and determine the presenter(s) or author(s) and 
timing of any presentation or publication related to this study and/or its results. Authorship will be 
determined by mutual agreement and in line with International Committee of Medical Journal 
Editors authorship requirements.

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15.
LIST OF REFERENCES
Benson AB, Ajani JA, Catalano RB, Engelking C, Kornblau SM, Martenson JA, et al.  
Recommended guidelines for the treatment of cancer treatment-induced diarrhea.  J Clin 
Oncol. 2004;22:2918-2926.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al.  New response 
evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).  Eur J Cancer. 
2009;45:228-247.
[Fulvestrant PI] Fulvestrant (Faslodex®) Prescribing Information.  AstraZeneca.  Last updated 
July 2018.
Helsten T, Elkin S, Arthur E, Tomson BN, Carter J, Kurzrock R.  The FGFR landscape in cancer: 
analysis of 4,853 tumors by next-generation sequencing.  Clin Cancer Res.  2016;22:259-267.
Hesketh PJ, Kris MG, Basch E, Bohlke K, Barbour SY, Clark-Snow RA, et al.  Antiemetics: 
American Society of Clinical Oncology Clinical Practice Guideline update.  J Clin Oncol.  
2017;35:3240-3261.
Jain VK, Turner NC.  Challenges and opportunities in the targeting of fibroblast growth factor 
receptors in breast cancer.  Breast Cancer Research.  2012;14:208.
Meric-Bernstam F, Arkenau H-T, Tran B, Bahleda R, Kelley RK, Hierro C, et al. 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.  2018;29(suppl_5):Abstract O-001. 
Razavi P, Chang MT, Xu G, Bandlamudi C, Ross DS, Vasan N, et al. The genomic landscape of 
endocrine-resistant advanced breast cancers.  Cancer Cell. 2018;34:427-438.
Smith TJ, Bohlke K, Lyman GH, Carson KR, Crawford J, Cross SJ, et al.  Recommendations for 
the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice 
Guideline Update.  J Clin Oncol. 2015;33:3199-3121.
Turner N, Pearson A, Sharpe R, Lambros M, Geyer F, Lopez-Garcia MA, et al. FGFR1
amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer. 
Cancer Research. 2010;70:2085-2094.
Turner N.  (2013) FGFR2 in breast cancer.  My Cancer Genome.  Available at URL: 
https://www.mycancergenome.org/content/disease/breast-cancer/fgfr2/. Last accessed: 
08 March 2019.

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16.
SIGNATURES OF SPONSOR AND PRINCIPAL INVESTIGATOR
16.1.
Declaration of the Sponsor
Study Title: A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring Fibroblast 
Growth Factor Receptor (FGFR) Amplifications
This study protocol was subject to critical review and has been approved by Taiho Oncology Inc. 
The information it contains is consistent with:

The current risk-benefit evaluation of the investigational product

The moral, ethical, and scientific principles governing clinical research as set out in the 
protocol, GCP, ICH Guidelines, and all applicable regulatory requirements
The Investigator will be supplied with details of any significant or new findings, including AEs, 
relating to treatment with the investigational product.
Sponsor’s Medical Officer
, MD, 
Taiho Oncology, Inc.
101 Carnegie Center, Suite 101
Princeton, NJ 08540 USA
Date:  07 June 2019

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16.2.
Declaration of the Investigator
Study Title:  A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring Fibroblast 
Growth Factor Receptor (FGFR) Amplifications
I have read the above protocol, appendices, and referenced documents. I understand the contents 
and intend to fully comply with all requirements. No changes will be made without formal 
authorization by Taiho Oncology, Inc. in the form of a protocol amendment. I will work according 
to the moral, ethical, and scientific principles governing clinical research as set out in the protocol, 
GCP, ICH Guidelines and all applicable regulatory requirements.
I confirm that I am not banned from conducting clinical research and I will immediately contact 
Taiho Oncology, Inc. if I cannot fulfill my obligations to complete this protocol.
Investigator
Signature:  ___________________________________________________
Name (block letters):  __________________________________________
Date:  __________________________________________

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APPENDIX A. ECOG PERFORMANCE STATUS
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
From: Oken MM, Creech, RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative 
Oncology Group. Am J Clin Oncol. 1982;5:649-55.

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APPENDIX B. 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 (ie, 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 C. CHILD-PUGH SCORE
Parameter
Points assigned
1
2
3
Ascites
Absent
Slight
Moderate
Bilirubin
<2 mg/dL (<34.2 µmol/L)
2 to 3 mg/dL (34.2 to 51.3 
µmol/L)
>3 mg/dL (>51.3 µmol/L)
Albumin
>3.5 g/dL (35 g/L)
2.8 to 3.5 g/dL (28 to 35 g/L)
<2.8 g/dL (<28 g/L)
Prothrombin time:
-
Seconds over control
-
INR
<4
<1.7
4 to 6
1.7 to 2.3
>6
>2.3
Encephalopathy
None
Grade 1 to 2
Grade 3 to 4
Modified Child-Pugh classification of the severity of liver disease according to the degree of 
ascites, the serum concentrations of bilirubin and albumin, the prothrombin time, and the degree of 
encephalopathy. A total Child-Turcotte-Pugh score of 5 to 6 is considered Child-Pugh Class A 
(well-compensated disease); 7 to 9 is class B (significant functional compromise); and 10 to 15 is 
class C (decompensated disease).

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APPENDIX D. 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/U
CM292362.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 < 
5fold increase in AUC or 50 –
80% decrease in CL
CYP3A
Boceprevir, clarithromycin, 
cobicistat, conivaptan, danoprevir 
and ritonavir, diltiazem, elvitegravir 
and ritonavir, grapefruit juice3, 
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 inducers1 or ≥ 80% 
decrease in AUC
Moderate Inducers2 50 –
80% decrease in AUC
CYP3A
Carbamazepine, enzalutamide, 
mitotane, phenytoin, rifampin, 
St. John’s wort3
Bosentan, efavirenz, 
etravirine, modafinil
1 A strong inducer is a drug that decreases the AUC of sensitive index substrates of a given 
metabolic pathway by ≥80%.
2 A moderate inducer is a drug that decreases the AUC of sensitive index substrates of a given 
metabolic pathway by ≥50% to <80%.
3 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 Substrates1
Moderate Sensitive Substrates2
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
1 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.
2 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.

TAS-120
Protocol TAS-120-201, Amendment 1 (Version 2.0)
Confidential - Proprietary Information
83
Example of Inhibitors for P-gp and BCRP
Transporters
Gene
Inhibitor
P-gp1
ABCB1
Amiodarone, carvedilol, 
clarithromycin, dronedarone, 
itraconazole, lapatinib, lopinavir and 
ritonavir, propafenone, quinidine, 
ranolazine, ritonavir, saquinavir and 
ritonavir, telaprevir, tipranavir and 
ritonavir, verapamil
BCRP2
ABCG2
Curcumin, cyclosporine A, 
eltrombopag
1 P-gp: (1) AUC fold-increase of digoxin ≥2 with co-administration and (2) in vitro inhibitor.
2 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.
Example of Substrates for P-gp and BCRP
Transporters
Gene
Substrate
P-gp1
ABCB1
Dabigatran, digoxin, fexofenadine
BCRP2
ABCG2
Rosuvastatin, sulfasalazine
1 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.
2 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.