A Phase 2 Study of Futibatinib in Patients With Specific FGFR Aberrations
Phase: PHASE2
Conditions: Advanced or Metastatic Solid Tumor, Advanced or Metastatic Gastric or Gastroesophageal Cancer, Myeloid or Lymphoid Neoplasms (MLN)
Sponsor: Taiho Oncology, Inc.

Oﬃcial Title: A Phase 2 Study of Futibatinib in Patients with Speciﬁc FGFR Aberrations
NCT ID: NCT04189445 
Document Date:    Protocol Amendment 2, 10 December 2021 
                                  Protocol Amendment 1, 07 February 2020

Clinical Study Protocol
A PHASE 2 STUDY OF FUTIBATINIB IN PATIENTS 
WITH SPECIFIC FGFR ABERRATIONS 
Futibatinib (TAS-120)
Protocol TAS-120-202
Issue Date: 08 November 2019 
Amendment 1:  07 February 2020
Amendment 2:  10 December 2021
IND Number: 145393
EudraCT Number: 2019-004084-49
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 (ICH), Good Clinical Practice (GCP) 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.

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SUMMARY OF CHANGES
The primary purpose of this amendment is to increase the sample size for patients in Cohort A. In 
addition, the benefit/risk sections and procedures in response to the COVID-19 pandemic have been 
modified and feedback from regulatory agencies has been incorporated. 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.
Section #
Section Name
Description of Change
Rationale
Throughout
Changed “trial” to “study” (except when referred to as a clinical trial)
Changed “subjects” and “participants” to “patients” (except when 
referring to healthy subjects)
Changed “study therapy/treatment/medication” to “study drug” 
(except when referring to overall study treatment period)
“Tumor response assessment” and “tumor assessment” changed to 
“response assessment”
Consistency 
throughout 
protocol
Throughout
In: Synopsis (Study Objectives and Endpoints – Cohorts A & B), 
Section 2 (Table 4), Section 11.5.3.1.2 (Secondary Efficacy Analyses)
Specified DOR as “Key Secondary” endpoint and other secondary 
endpoints as “Additional Secondary” for Cohorts A & B
Clarify key 
secondary 
endpoint
Throughout
Changed “the signing of the ICF” to “receiving documented informed 
consent”, “the ICF is signed” / “from the day of ICF signature” / 
“from when the patient signs the ICF” to “informed consent has been 
documented”, and “completion of the ICF” to “documented consent”
To align with 
COVID-19 
updates in this 
amendment
Synopsis
Objectives and 
Endpoints and 
Table 5
“PopPK and exposure response will be analyzed from blood samples 
collected during treatment.” in Exploratory Endpoint section changed 
to “PK data will be pooled with data from other cohorts or other 
studies for a popPK analysis. The relationship between popPK model 
derived exposure and response will be explored.”
Align with 
protocol 
amendment 
updates
Synopsis
Number of Patients
Updated number of patients in Cohort A from 60 to 100.
Obtain additional 
safety and efficacy 
data
Synopsis and 4.1. 
Inclusion Criteria 
Changed “gastric or GEJ cancer” to “gastric or GEJ adenocarcinoma” 
for Inclusion #5.b.i
Added “for Cohorts A and B and bone marrow tissue for Cohort C” to 
Inclusion #6
Clarified sample 
collection 
Synopsis
Evaluation Criteria
Deleted “on-site” from “on-site response assessments” for Cohorts A 
and B
Updated PK description for Cohort C
Clarified 
evaluation criteria

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Section #
Section Name
Description of Change
Rationale
Synopsis
Statistical Methods
The sample size in Cohort A was increased from 60 to 100 patients. 
Updated total number of patients from 115 to 155. 
Added “Additional interim analyses may be performed if required for 
regulatory purposes.” to interim analysis section.
Added “per RECIST 1.1” to objective response rate definition in 
primary efficacy analysis for Cohorts A and B.
Updated overall response rate and disease control rate definition in 
secondary efficacy analyses section. 
Added “Population PK and Exposure-Response Analyses” section.
Obtain additional 
safety and efficacy 
data and clarify 
timepoints for 
analysis
Synopsis
Population PK and 
Exposure-Response 
Analyses
Added section. 
Clarified PK 
analyses
Study Schema 
(Synopsis and 
Section 3.1) 
Updated Cohort A with new sample size and revised GEJ cancer to 
GEJ adenocarcinoma in Cohort B.
Align with 
protocol 
amendment 
updates
Schedule of Events 
Added “The first study drug administration will occur on C1D1.” 
Clarified start date
Schedule of Events
Table 2 (Cohort C) 
“Tumor tissue sample” deleted.
PET scan notes updated and added “(+/- 7 days)”.
Added “visit” to lymph node biopsy
“Bone marrow biopsy” changed to “Bone marrow tissue submission” 
and assessment notes updated and added that archival sample can be 
used for baseline submission.
Clarified schedule 
of events
Schedule of Events
Table 3 (Study 
Extension)
Deleted ECOG performance status assessment
Added pregnancy testing during treatment period and removed from 
safety follow-up visit.
Align with 
protocol 
amendment 
updates
List of 
Abbreviations
Updated with additional terms
Align with 
protocol 
amendment 
updates
3.4 Study 
Completion and 
Study Extension
Added “in either Cohort A, B, or C, whichever comes last” to first 
bullet.
Added “The Sponsor will inform study sites when a Study Extension 
phase is initiated.”
Clarified study 
extension criteria
3.6. End of Trial 
Added “The end of the trial will occur when all patients (including 
patients in the Study Extension phase, if any) have discontinued 
treatment and undergone all protocol-mandated assessments 
(including the 30-day Safety Follow-Up Visit).”
Clarified end of 
study definition
4.2. Exclusion 
Criteria and 
Synopsis
Change “and” to “or” in Exclusion #5
Added to 
exclusion criteria

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Section #
Section Name
Description of Change
Rationale
Table 7
Changed “permanently discontinue futibatinib” to “consider 
permanent discontinuation of futibatinib” in Grade 3 toxicity
Deleted “however” in Grade 3 toxicity
Clarify 
discontinuation 
Table 8 
Removed “Grade” column. 
Added lab values in rows 3 and 4. 
Changed “it’s” to “serum phosphate has” in row 4.
Footnote removed “c” and updated footnotes accordingly.
Removed “regardless of the grade (including Grade 1 and 2)” from 
Footnote d (currently Footnote c). 
Removed grading 
categories for 
hyper-
phosphatemia
5.4.3 Drug 
Interactions
Updated drug interaction information 
Clarified drug 
interactions
5.6.4 
Accountability
Added “The patient will be provided a diary to record when they have 
taken the study drug each day.”
Clarified study 
drug 
accountability
6.0 Study 
Assessments 
Serum Chemistry 
Removed “bicarbonate” from Assessment list.
Corrected 
laboratory tests
6.0 Study 
Assessment
AE monitoring 
Removed “through 30 days” and added “until Safety Follow-Up 
Visit” from Assessment list.
Clarified safety 
follow-up
6.3 Considerations 
during the COVID-
19 Pandemic 
Added section to include text related to implementation of alternate 
procedures for study conduct during COVID-19. 
Added in 
compliance with 
FDA and EMA 
guidelines
7. Pharmaco-
kinetics
Updated PK description 
Clarified PK 
analysis
8.1.1 Efficacy 
Criteria
Added “Planned time points for all efficacy assessments are provided 
in the Schedule of Events”. 
Deleted “Primary objective and additional secondary objectives will 
be assessed by an IRC.”
Added 
clarification
8.1.3 Tumor 
Definitions
Added “The following definitions are outlined according to RECIST 
1.1 criteria:”
Added 
clarification
8.3 Efficacy 
Endpoints
Deleted Table 15 and explanatory text.
Referred to Table 4, Section 11.5.3.1.2, and SAP.
Added 
clarification 
9.1 Adverse Events 
Added “unless the Investigator deems it related to study drug.”
Deleted “For all AEs that occur between signing ICF, there is no need 
to record those that are unrelated unless it is mandatory by local 
regulations.”
Added 
clarification 

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Section #
Section Name
Description of Change
Rationale
9.4.1 Definitions of 
Serious Adverse 
Events
Deleted “possibly” statement of SAEs resulting in death.
Added 
clarification
9.4.2 Reporting of 
Serious Adverse 
Events (within 24 
hours)
Deleted “of the Safety Follow-up Period”.
Added “immediately and no later than” and deleted “within”.
Added paragraph on SAE reporting outside of follow-up period.
Added 
clarification
9.4.3 Reporting of 
Deaths (within 24 
hours) 
Added “immediately and no later than” and deleted “within”.
Added “Death due to disease progression is not a reportable event, 
unless the Investigator deems it related to study drug. In the latter 
case, the event must be reported within 24 hours from the times the 
Investigator first becomes aware of the death.”
Added 
clarification 
regarding 
reportable deaths
11.1 Estimation of 
Sample Size
Added subheading for each cohort.
The sample size in Cohort A was increased from 60 to 100 patients. 
Updated total number of patients from 115 to 155. Included additional 
justification for increase in sample size.
Updated Table 15 to reflect n=100.
Obtain additional 
safety and efficacy 
data
11.2 Timing of 
Analysis
Changed heading from “Planned Interim Analysis” to “Timing of 
Analysis”.
Added detailed information about final analyses for each cohort.
Clarify final 
analyses
11.5 Statistical 
Analysis
Added “This section outlines the statistical methodology to be used to 
summarize the study results. A more detailed methodology for 
summary and stastical analyses of the data collected in this study are 
documented in the SAP. The SAP will be prepared as a separate 
document by the Sponsor.”
Added 
clarification
11.5.3 Efficacy 
Analyses
Updated table references to Table 4 and Table 5.
Align with 
amendment
11.5.5 
Pharmacokinetic 
Analysis
Changed “concentration vs time data” to “PK data”
Added 
clarification
14.2 Documented 
Informed Consent
Changed Section title.
Replaced “written” with “documented” throughout section.
Deleted “sign”.
To align with 
COVID-19 
updates in this 
amendment
16 References 
Updated reference list.
Revised for 
ongoing study
Appendix C. 
Replaced reference to FDA Draft Guidance for Industry, Clinical 
Drug Interaction Studies – Study Design, Data Analysis, and Clinical 
Implications, October 2017 with FDA Drug Development and Drug 
Interactions | Table of Substrates, Inhibitors and Inducers. Content 
current as of: 03/10/2020
Revised reference 
to current FDA 
guidance 
Appendix C
Added CYP3A Substrates table.
Added to 
appendix

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STUDY SUMMARY
Protocol Synopsis
Protocol Title: 
A Phase 2 Study of Futibatinib in Patients with Specific FGFR Aberrations
Rationale:
Fibroblast growth factor receptor (FGFR) signaling plays a crucial role in cancer cell proliferation, 
migration, angiogenesis, and survival. Recent studies have uncovered increasing evidence that 
deregulated FGFRs can function as driving oncogenes in certain tumor types, maintaining the malignant 
properties of cancer cells. When FGFRs are amplified, rearranged, or undergo fusion, aberrant activation 
of downstream pathways results in mitogenic, mesenchymal, and antiapoptotic responses in cells. 
Therefore, FGFRs are attractive targets for therapeutic intervention in cancer treatment.
The Phase 2 study described in this protocol will evaluate the efficacy and safety of futibatinib in patients 
with FGFR aberrations in 3 distinct cohorts. Patients will be enrolled into 1 of 3 cohorts: patients with 
advanced, metastatic, or locally-advanced solid tumors harboring FGFR rearrangements (excluding 
primary brain tumors and intrahepatic cholangiocarcinoma [iCCA]); patients with gastric or 
gastro-esophageal junction (GEJ) cancer harboring FGFR2 amplification; and patients with myeloid or 
lymphoid neoplasms (MLN) harboring FGFR1 rearrangements.

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Study Objectives and Endpoints:
Cohorts A and B
Primary
To evaluate the objective response rate (ORR) in 
patients with solid tumors harboring FGFR 
rearrangements or gastric cancer (including GEJ 
cancer) harboring FGFR2 amplifications based on 
independent central review of radiologic images (IRC)
ORR, defined as the proportion of patients experiencing a 
best overall response of partial response (PR) or complete 
response (CR) (per Response Evaluation Criteria in Solid 
Tumors, Version 1.1 [RECIST 1.1]), based on IRC 
Secondary 
Key secondary:

To evaluate duration of response (DOR) based on 
IRC 
Additional secondary:

To evaluate ORR based on Investigator 
assessment 

To evaluate progression-free survival (PFS), 
disease control rate (DCR), and overall survival 
(OS)

To assess safety and tolerability

DOR defined as the time from the first documentation 
of response (CR or PR per RECIST 1.1 based on 
IRC) to the first documentation of objective tumor 
progression or death due to any cause, whichever 
occurs first, based on IRC

ORR, defined as the proportion of patients 
experiencing a best overall response of partial 
response of PR or CR (per RECIST 1.1), based on 
Investigator assessment

DCR, defined as the proportion of patients 
experiencing a best overall response of stable disease 
(SD), PR, or CR (per RECIST 1.1), based on IRC 

PFS, defined as the time from first dose of study drug 
to the date of death (any cause) or disease progression 
(based on IRC), whichever occurs first

OS, defined as the time from the date of first dose to 
the death date

Safety based on reported AEs and on-study laboratory 
parameters, graded according to the National Cancer 
Institute—Common Terminology Criteria for 
Adverse Events, Version 5.0 (NCI-CTCAE V5.0). 
Exploratory

To assess the possible impact of genetic 
alterations or other laboratory abnormalities on the 
efficacy of futibatinib 

To assess the population pharmacokinetics 
(PopPK) and exposure response

Assessment of genetic alterations in circulating tumor 
DNA (ctDNA), tumor biopsy, and/or plasma samples, 
and their possible correlation with clinical outcome.

PK data will be pooled with data from other cohorts 
or other studies for a popPK analysis.

The relationship between popPK model derived 
exposure and response will be explored. 

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Cohort C
Overall Objective
The overall objective of Cohort C is to assess the clinical activity of futibatinib as monotherapy in the treatment of 
patients with myeloid/ lymphoid neoplasms (MLN) harboring FGFR1 rearrangements.
Primary
To evaluate complete response rate 
CR rate, defined as the proportion of patients who 
achieved a CR
Secondary 

To evaluate:
o
ORR
o
CR + complete response with incomplete 
hematological recovery (CRi) rate 
o
Complete or partial cytogenetic responses 
(CCyR or PCyR) rate
o
Duration of CR
o
Duration of CR+CRi
o
DOR
o
Time-to-events 

To assess the safety and tolerability

ORR, defined as the proportion of patients who 
achieved a CR, CRi, or PR

CR+CRi rate, defined as the proportion of patients 
who achieved a CR or CRi 

CCyR rate, defined as the proportion of patients who 
achieved CCyR

PCyR rate, defined as the proportion of patients who 
achieved PCyR

Duration of CR defined as the time from the first 
documentation of CR to the first documentation of 
objective tumor progression or death due to any 
cause, whichever occurs first

Duration of CR+CRi defined as the time from the 
first documentation of CR/CRi to the first 
documentation of objective tumor progression or 
death due to any cause, whichever occurs first

DOR defined as the time from the first 
documentation of CR, CRi, or PR to the first 
documentation of objective tumor progression or 
death due to any cause, whichever occurs first 

PFS, defined as the time from first dose of study drug 
to the date of death (any cause) or disease 
progression, whichever occurs first

Relapse-free survival (RFS), defined as the time from 
the first documentation of CR to the first 
documentation of disease relapse or death due to any 
cause, whichever occurs first. 

Event-free survival (EFS) (leukemia presentation 
only), defined as the time from first dose of study 
drug to treatment failure, disease relapse after CR, or 
patient death from any cause. 

OS, defined as the time from the date of first dose to 
the death date. 

Safety based on reported AEs and on-study 
laboratory parameters, graded according to the 
NCI-CTCAE V5.0

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Exploratory

To assess the pharmacodynamic effects of 
treatment with futibatinib

To assess the association of response and 
mechanisms of resistance in tumor tissue biopsies 
and/or blood

To assess the popPK and exposure response

Changes in pharmacodynamic markers assessed in 
bone marrow tissue biopsies.

Exploratory association of tissue and/or blood 
markers with tumor efficacy endpoints and/or tumor 
resistance to futibatinib.

PK data will be pooled with data from other cohorts 
or other studies for a popPK analysis.

The relationship between popPK model derived 
exposure and response will be explored.
Overall Design:
Study TAS-120-202 is an open-label, multinational, 3-arm, Phase 2 study evaluating the efficacy, safety, 
tolerability, pharmacokinetics (PK), and pharmacodynamics of futibatinib in patients with FGFR 
aberrations. Eligible patients will be assigned to 1 of 3 treatment cohorts based on diagnosis and FGFR 
gene aberration status. 
Patients will receive futibatinib at an oral dose of 20 mg once a day on a continuous 28-day cycle. 
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, response 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, the patient withdraws consent, or the study is terminated early by 
the Sponsor.
Additional cohorts may be added in the future in case of new emerging efficacy data. This change will be 
implemented through a protocol amendment which will describe the rationale for the addition(s).
Number of Patients: 
The study will enroll approximately 100 patients with advanced, metastatic, or locally advanced solid 
tumor harboring FGFR rearrangements, except for primary brain tumor or iCCA); 35 patients with 
advanced, metastatic, or locally advanced gastric or GEJ cancer harboring FGFR2 amplification; and 
20 patients with MLN harboring FGFR1 rearrangements.
Entry Criteria: 
Inclusion Criteria
1.
Provide documented informed consent (refer to Section 6.3)
2.
≥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

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4.
Has recovered from the acute toxic effects of prior anticancer therapy to baseline or Grade 1 (except 
toxicities which are not clinically significant such as alopecia)
5.
Known FGFR aberration status and tumor type that meet all of the criteria for 1 of the following 
cohorts: 
a.
Cohort A
i.
Histologically confirmed, locally advanced, advanced, or metastatic solid tumors 
harboring a FGFR1-4 rearrangement determined in tumor tissue using next-generation 
sequencing (NGS), fluorescence in situ hybridization (FISH), or other assays that can 
determine gene rearrangements in tumor tissues. Patients with primary brain tumor or 
iCCA are not eligible.
ii.
Measurable disease per RECIST 1.1 
iii.
Had disease progression/recurrence after standard treatment for their advanced or 
metastatic cancer 
b.
Cohort B
i.
Histologically confirmed, locally advanced, advanced, or metastatic gastric or GEJ 
adenocarcinoma harboring a FGFR2 amplification. The tumor must have an 
FGFR2/CEN10 ratio of ≥5 or an FGFR2 copy number ≥10 signals per cell determined in 
tumor tissue using NGS, FISH, or other assays that can determine gene amplification in 
tumor tissues. 
ii.
Measurable disease per RECIST 1.1
iii.
Received at least 2 prior systemic regimens for advanced/metastatic disease
iv.
Experienced disease progression/recurrence during or after the most recent prior systemic 
treatment for advanced/metastatic gastric or GEJ cancer 
c.
Cohort C
i.
Confirmed MLN with a FGFR1 rearrangement as defined by WHO criteria 
ii.
Not a candidate for hematological stem cell transplant (HSCT) or relapsed after HSCT 
and donor lymphocyte infusion, and progressed and not a candidate for other therapies
6.
Has archival or fresh tumor tissue (preferably in block format) for Cohorts A and B and bone marrow 
tissue for Cohort C available to send to central laboratory.
7.
Adequate organ function as defined by the following criteria:
a.
Cohorts A and B:
i.
Absolute neutrophil count (ANC) ≥1.0 × 109/L
ii.
Platelet count ≥75,000/mm3 (≥75 × 109/L) 
iii.
Hemoglobin ≥9.0 g/dL
iv.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 × upper limit 
of normal (ULN); if liver function abnormalities are due to underlying liver metastasis, 
AST and ALT ≤5.0 × ULN.
v.
Total bilirubin ≤1.5 × ULN, or ≤3.0 × ULN for patients with Gilbert’s syndrome.
vi.
Creatinine clearance (CrCl) (calculated or measured value): ≥40 mL/min. For calculated 
CrCl, use the Cockcroft-Gault formula (Section 6).
vii. Phosphorus <1.5 ULN
b.
Cohort C
i.
ALT and AST ≤3.0 × ULN; if liver function abnormalities are due to underlying liver 
metastasis, AST and ALT ≤5.0 × ULN.

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ii.
Total bilirubin ≤1.5 × ULN, or ≤3.0 × ULN for patients with Gilbert’s syndrome.
iii.
CrCl (calculated or measured value): ≥40 mL/min. For calculated CrCl, use the 
Cockcroft-Gault formula (Section 6).
iv.
Phosphorus <1.5 ULN
8.
Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test prior to 
administration of the first dose of futibatinib. Female patients are not considered to be of 
child-bearing potential if they are post-menopausal, defined as no menses for 12 months without an 
alternative medical cause or permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral 
oophorectomy). 
9.
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 or longer based on local requirements.
10. Ability to take medications orally (feeding tube is not permitted).
11. Willing and able to comply with scheduled visits and study procedures.
Exclusion Criteria
1.
Currently receiving an investigational drug in a clinical trial or participating in any other type of 
medical research judged not to be scientifically or medically compatible with this study. If a patient is 
currently enrolled in a clinical trial involving non-approved use of a device, then agreement with the 
Investigator and the Sponsor’s Medical monitor is required to establish eligibility.
2.
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.
3.
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.
4.
Treatment with any of the following within the specified time frame prior to the first dose of 
futibatinib:
a.
Major surgery within 4 weeks (surgical incision should be fully healed)
b.
Radiotherapy for extended field within 4 weeks or limited field radiotherapy within 2 weeks
c.
A drug that has not received regulatory approval for any indication within 14 or 21 days of 
treatment for a nonmyelosuppressive or myelosuppressive agent, respectively.
5.
Received strong inhibitors or inducers of CYP3A4 within 2 weeks of first dose
6.
Prior treatment with an FGFR inhibitor
7.
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 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

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f.
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may 
increase the risk associated with study participation or futibatinib administration, or may interfere 
with the interpretation of study results, and in the judgment of the Investigator would make the 
patient inappropriate for entry into this study
8.
Active central nervous system (CNS) metastasis and/or carcinomatous meningitis. Patients with 
previously treated brain metastases that are clinically and radiologically stable (for at least 4 weeks 
prior to enrollment) are eligible.
9.
Known additional malignancy that is progressing or has required active treatment within the past 
2 years. Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or 
carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially 
curative therapy are not excluded.
10. Pregnant or breastfeeding.
Evaluation Criteria:
Efficacy
Cohorts A and B
For patients in Cohorts A and B, response 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). Primary objective and additional secondary objectives will be 
assessed by an IRC.
Results of the local 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 drug decisions.
Cohort C
Efficacy will be assessed based on Investigators’ assessment of imaging, bone marrow, peripheral blood, 
and extramedullary disease. Depending on the presentation response will be determined based on 
Treatment Response Criteria for MDS/MPN (Savona et al. 2015), Response Evaluation Criteria in 
Lymphoma (RECIL 2017) (Younes et al. 2017), and International Working Group (IWG) response 
criteria for AML (Cheson et al. 2003).
A review of the response assessments will be conducted by an adjudication committee.
Safety
The assessment of safety will be based on the incidence of treatment-emergent adverse events (TEAEs) 
and on-study laboratory parameters. Grading of TEAEs will be performed using NCI-CTCAE V5.0.
Pharmacokinetics (PK)
The PK population will consist of all patients who received at least one dose of futibatinib and have 
evaluable PK data. 
Pharmacodynamics
Genetic aberrations will be tested using analytically validated assay on NGS or similar technology at a 
central laboratory.

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A blood sample will be collected to assess FGF/FGFR aberrations in ctDNA. In addition to assessing 
ctDNA as a pharmacodynamic biomarker, samples or a set of samples will be used to verify its utility as 
an alternative to tumor tissues for the potential companion diagnostic. Samples will be collected and 
stored, as per the laboratory manual, and analyzed in batches.
Archival or fresh tumor/bone marrow samples will be collected during screening 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 after study completion for 
future testing.
Statistical Methods:
Determination of Sample Size
Approximately 100 patients with solid tumors harboring FGFR rearrangements will be enrolled in 
Cohort A. Sample size considerations are based on differentiating a null ORR of 10% with a target ORR 
of 25%. Assuming the true ORR is 25%, the study has over 90% power to reject the null hypothesis that 
the true ORR is ≤10%, considering a 2-sided alpha of 5%.
A 2-stage Simon design (Simon 1989) will be used for futility assessment, comparing a poor response of 
≤10% vs a promising response of ≥25%, at a 5% 1-sided significance level and approximate 90% power.

In Stage 1 (futility assessment), enrollment will include 35 patients and accrual will continue 
to Stage 2, if at least 4 (11.4%) of 35 patients respond (CR or PR).

If the Stage 1 futility boundary is exceeded, Stage 2 will be open and require at least 
25 additional patients. To further provide a more precise estimate of objective response rate 
and a better evaluation of safety profile, a total of 100 patients will be enrolled.
Approximately 35 patients with gastric or GEJ cancer harboring FGFR2 amplification will be enrolled in 
Cohort B. Sample size considerations are based on differentiating a historical control ORR of 10% or less, 
with a target ORR of 35%. Assuming the true ORR is 35%, the cohort has approximately 96% power to 
reject the null hypothesis that the true ORR is ≤10%, considering a 2-sided alpha of 5%. With a sample 
size of 35, observing at least 8 responders will have a 95% CI lower bound excluding 10% (ORR of 23% 
with 95% CI [10.4%-40.1%]).
Approximately 20 patients with MLN harboring FGFR1 rearrangements will be enrolled in Cohort C. 
Sample size considerations are based on differentiating a historical control CR rate of 10% or less with a 
target CR rate of 50%. Assuming the true CR rate is 50%, the cohort has over 95% power to reject the 
null hypothesis that the true CR rate is ≤10%, considering a 2-sided alpha of 5%. Observing at least 
6 responders out of 20 treated patients will have a 95% CI lower bound excluding 10% (CR rate of 30% 
with 95% CI (11.9%-54.3%).
Interim Analysis
The Sponsor will review the data at the time Cohort A has the required number of patients to determine if 
the cohort should continue. Additional interim analyses may be performed if required for regulatory 
purposes.

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Efficacy Analyses
Cohorts A and B
Primary Efficacy Analysis
Objective response rate is defined as the proportion of patients with objective evidence of CR or PR (per 
RECIST 1.1). The primary evaluation of ORR will be based on an independent central review of 
radiologic images. At the analysis stage, the best objective response will be assigned for each patient as 
the best response recorded after initiation of study drug 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.
Secondary Efficacy Analyses
Overall response rate and disease control rate (DCR) based on Investigator assessment will be determined 
(per RECIST 1.1) as described for the primary analysis of ORR based on independent central review of 
radiologic images (Section 11.5.3.1.1). 
Duration of response will only be evaluated in patients with an 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 
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 response 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 response 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 anticancer therapy without a prior reported progression will be censored at 
the last response assessment prior to initiation of the subsequent anticancer therapy.
Overall survival will be analyzed in a similar manner to PFS. In the absence of confirmation of death or 
for patients who are alive as of the OS cut-off date, survival time will be censored at the last known date 
that the patient was alive.
Cohort C
Primary Analysis
Complete response rate defined as the proportion of patients who achieved a CR will be calculated and 
the exact 2-sided CI will also be derived using the Clopper Pearson methodology.
Secondary Analyses
The overall response, CR+CRi (leukemia presentation only), CCyR, and PCyR rates will be calculated 
and the exact 2-sided CIs will also be derived using the Clopper-Pearson methodology.
Duration of CR (only in patients who achieved a CR), duration of CR+CRi (only in patients who 
achieved a CR/CRi [leukemia presentation only]), and duration of response (only in patients with an 
objective response of CR, CRi [leukemia presentation only], or PR) will be estimated using the 
Kaplan-Meier method. Patients who are alive and progression-free as of the analysis cut-off date will be 

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censored at their last evaluable 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 response 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 response 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 anticancer therapy without a prior reported progression will be censored at 
the last response assessment prior to initiation of the subsequent anticancer therapy.
Relapse-free survival will only be evaluated in patients with an objective response of CR and measured 
from the first date of achieving CR until the first date of relapsed disease or death from any cause, 
whichever occurs first. Patients who die without a reported disease relapse will be considered to have 
relapsed on the date of their death. Patients who did not relapse or die will be censored on the date of their 
last response assessment. Patients who started any subsequent anticancer therapy without a prior reported 
relapse will be censored at the last response assessment prior to initiation of the subsequent anticancer 
therapy.
Event-free survival (EFS) will be estimated only for patients with leukemia presentation using the 
Kaplan-Meier method. EFS is defined as the time from first dose of study drug to treatment failure, 
relapse after CR (if applicable), or death from any cause, whichever occurs first. For a patient with none 
of these events before the end of study follow-up, observation of EFS is censored at the date of last 
contact prior to the analysis cut-off date. If the patient does not achieve a CR, EFS is defined as the point 
of treatment failure or death, whichever comes first. Treatment failure for EFS is defined as PD in this 
study.
Overall survival will be analyzed in a similar manner to PFS. In the absence of confirmation of death or 
for patients who are alive as of the OS cut-off date, survival time will be censored at the last known date 
that the patient was alive.
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 V5.0, 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 futibatinib. In addition, separate summaries of SAEs 
and Grade 3 and 4 AEs will be presented.
For all AEs that occurred between receiving documented informed consent 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.

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Hematological and chemistry laboratory parameters will be graded according to the NCI-CTCAE V5.0 
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 
electrocardiogram findings will be presented by patient.
Population PK and Exposure-Response Analyses
PK data will be pooled with data from other studies for a popPK analysis. The relationship between 
popPK model derived exposure and response will be explored for each cohort. The popPK and 
Exposure-Response (E-R) analyses will be described in a separate popPK/E-R Analysis Plan.  
Pharmacodynamic Analyses
Pharmacodynamic and biomarker data will be summarized descriptively using all patients in the 
Pharmacodynamic/Biomarker Evaluable Set who have evaluable data available.

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Study Schema

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Schedule of Events
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 
72 hours prior to dosing do not need to be repeated on Cycle 1 Day 1 (C1D1). The first study 
drug administration will occur on C1D1. The End of Treatment (EOT) visit must be performed 
within 7 days after a decision is made to discontinue study drug (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). Required assessments for patients in Cohorts A and B are presented in 
Table 1 and for Cohort C in Table 2. Required assessments during the Study Extension phase are 
presented in Table 3 for all cohorts.

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Table 1: 
Schedule of Events (Cohorts A and B)
Treatment Period (1 cycle =28 days)
Cycle 1
Cycle ≥2
Evaluation
Screening
(Within 28 days of 1st dose)
D1
(±3 days)
D8
(±3 days)
D15
(±3 days)
D22
(±3 days)
D1
(±3 days)
End of Cycle
(±7 days)
End of Treatment
(+7 days)
Safety Follow-up
30 days after last dose (+7 days)
Survival Follow-up Period
(every 12±2 weeks)
Notes
Documented informed consent
X
Documented informed consent will be obtained prior to any 
study-related assessments or procedures.
Review eligibility criteria
X
Demographics/medical history
X
Review of baseline signs and 
symptoms
X
Prior & concomitant 
medications, AE assessments
Physical examination
X
X
X
X
X
Within 24 hours prior to dosing.
Vital signs
X
X
X
X
X
Heart rate, blood pressure, body temperature, and respiration 
rate.
Height and weight
X
X
X
X
X
Height at screening only.
ECOG performance status
X
X
X
X
X
Within 24 hours prior to dosing.
12-Lead electrocardiogram 
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
X
Within 24 hours prior to dosing. 
More frequent assessments may be performed if clinically 
indicated
Coagulation
X
X
X
X
X
Within 24 hours prior to dosing.
Chemistry (serum or plasma)
X
X
X
X
X
X
X
X
Within 24 hours prior to dosing.

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Treatment Period (1 cycle =28 days)
Cycle 1
Cycle ≥2
Evaluation
Screening
(Within 28 days of 1st dose)
D1
(±3 days)
D8
(±3 days)
D15
(±3 days)
D22
(±3 days)
D1
(±3 days)
End of Cycle
(±7 days)
End of Treatment
(+7 days)
Safety Follow-up
30 days after last dose (+7 days)
Survival Follow-up Period
(every 12±2 weeks)
Notes
Pregnancy test
X
Within 
7 days
X
Serum pregnancy test required for WOCBP. Additional 
testing may be required by local regulations.
Ophthalmological examination
X
See 
Note
Examination to be performed by an ophthalmologist or 
qualified delegate at screening, 4-6 weeks after first dose, and 
as indicated if symptoms or signs of mineral deposits.
PK blood sampling
See 
Note
Pre-dose (from -30 min to just before dose), 1 h±30 min 
post-dose, and 3 h±30 min post-dose
ctDNA blood samples
X
X
Tumor tissue sample 
X
Archival or fresh tumor biopsy
Response assessments 
(CT/MRI) 
X
X
X
X
X
At baseline and the end of every 2 cycles ±7 days), or as 
clinically indicated, until radiologic PD or initiation of new 
anticancer therapy (whichever comes first). 
For patients who discontinue treatment for reasons other than 
radiographic disease progression, imaging will be performed 
at EOT, (if the prior scan was performed ≥9 weeks) and 
during Survival Follow-up until radiologic disease progression 
or initiation of new anticancer therapy (whichever occurs first) 
unless patient withdraws consent.
Survival status
X
For all patients, unless patient withdraws consent or the study 
is terminated early by the Sponsor. 

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Treatment Period (1 cycle =28 days)
Cycle 1
Cycle ≥2
Evaluation
Screening
(Within 28 days of 1st dose)
D1
(±3 days)
D8
(±3 days)
D15
(±3 days)
D22
(±3 days)
D1
(±3 days)
End of Cycle
(±7 days)
End of Treatment
(+7 days)
Safety Follow-up 30 days 
after last dose (+7 days)
Survival Follow-up Period
(every 12±2 weeks)
Notes
Chemistry (serum or plasma)
X
X
X
X
X
X
X
X
Within 24 hours prior to dosing.
Pregnancy test
X
Within 
7 days
X
Serum pregnancy test required for WOCBP. 
Additional testing may be required by local 
regulations.
Ophthalmological 
examination
X
See 
Note
Examination to be performed by an 
ophthalmologist or qualified delegate.
At screening, 4-6 weeks after first dose, and as 
indicated if symptoms or signs of mineral 
deposits.
PK blood sampling
See 
Note
Pre-dose (from -30 min to just before dose), 
1 h±30 min post-dose, and 3 h±30 min post-dose
ctDNA blood samples
X
X
CT/MRI
X
X
X
X
X
At baseline and the end of every 2 cycles 
(±7 days), or as clinically indicated, until 
radiologic PD or initiation of new anticancer 
therapy (whichever comes first). 
For patients who discontinue treatment for 
reasons other than radiographic disease 
progression, imaging will be performed at EOT, 
(if the prior scan was performed ≥9 weeks) and 
during Survival Follow-up until radiologic 
disease progression or initiation of new 
anticancer therapy (whichever occurs first) unless 
patient withdraws consent.

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Treatment Period (1 cycle =28 days)
Cycle 1
Cycle ≥2
Evaluation
Screening
(Within 28 days of 1st dose)
D1
(±3 days)
D8
(±3 days)
D15
(±3 days)
D22
(±3 days)
D1
(±3 days)
End of Cycle
(±7 days)
End of Treatment
(+7 days)
Safety Follow-up 30 days 
after last dose (+7 days)
Survival Follow-up Period
(every 12±2 weeks)
Notes
PET scan
X
See Note
PET scan to be performed at baseline visit, end of 
Cycle 1 (± 7 days) if baseline is abnormal, and as 
clinically indicated for response assessment. 
Lymph node biopsy
X
See Note
Recommended at baseline visit if lymph node 
present at baseline and progression
Bone marrow tissue 
submission 
X
See Note
Archival or fresh bone marrow biopsy tissue 
sample needs to be submitted at baseline visit. In 
addition, bone marrow biopsy should be 
performed in case of normalization of peripheral 
blood count during the futibatinib treatment. In 
absence of peripheral blood count normalization, 
biopsy to be performed every 6 months. 
Additional biopsies to be performed as clinically 
indicated.
Survival status
X
For all patients, unless patient withdraws consent 
or the study is terminated early by the Sponsor. 

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Table 3:
Schedule of Events – Study Extension Phase: All Cohorts
Treatment Period
At Least Every 3 Cycles
Safety Follow-up
30 (+7) Days After last Dose
Notes
Physical examination
X
X
Within 24 hours prior to dosing on D1
Vital signs
X
X
Heart rate, blood pressure, body temperature, and respiration rate.
Weight
X
X
Ophthalmological examination
(X)
X
As needed due to local requirements, physician judgment, and/or 
symptoms or signs of mineral deposits.
12-Lead electrocardiogram 
X
X
Hematology and coagulation
X
X
Within 24 hours prior to dosing on D1
Chemistry (serum or plasma)
X
X
Within 24 hours prior to dosing on D1
Pregnancy test
X
More frequently if required by local regulations. 
Prior & concomitant 
medications, AE assessments
(X)
X
Collect from the time main informed consent is signed through 30 days 
after administration of the last dose of study drug or until the start of new 
anticancer therapy, whichever is earlier.  
Response assessments/imaging
(X)
All Cohorts: CT/MRI scans at baseline and the end of every 2 cycles 
(±7 days), or as clinically indicated, until radiologic PD or initiation of new 
anticancer therapy (whichever comes first).
Cohort C only: bone marrow, PET, and other response assessments as 
clinically indicated.

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TABLE OF CONTENTS
SUMMARY OF CHANGES...........................................................................................................2
STUDY SUMMARY ......................................................................................................................6
Protocol Synopsis ............................................................................................................................6
Study Schema.................................................................................................................................17
Schedule of Events.........................................................................................................................18
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS................................................31
1.
INTRODUCTION......................................................................................................35
1.1.
Disease Background ...................................................................................................35
1.2.
Futibatinib (TAS-120) ................................................................................................36
1.2.1.
Clinical Overview.......................................................................................................36
1.3.
Summary of Study Rationale......................................................................................37
2.
OBJECTIVES AND ENDPOINTS............................................................................38
3.
INVESTIGATIONAL PLAN.....................................................................................40
3.1.
Overview of Study Design..........................................................................................40
3.2.
Scientific Rationale for Study Design ........................................................................41
3.3.
Study Periods and Visits for Each Patient..................................................................41
3.3.1.
Screening Period.........................................................................................................41
3.3.2.
Treatment Period and End of Treatment Visit............................................................41
3.3.3.
Safety Follow-Up Period and 30-Day Safety Follow-Up Visit..................................41
3.3.4.
Post-Discontinuation Considerations..........................................................................42
3.3.5.
Survival Follow-Up ....................................................................................................42
3.4.
Study Completion and Study Extension.....................................................................42
3.5.
Patient Enrollment ......................................................................................................43
3.6.
End of Trial.................................................................................................................43
4.
SELECTION AND WITHDRAWAL OF PATIENTS..............................................44
4.1.
Inclusion Criteria ........................................................................................................44
4.2.
Exclusion Criteria.......................................................................................................45
4.3.
Screen Failure.............................................................................................................47
4.4.
Discontinuation of Treatment.....................................................................................47
4.5.
Withdrawal from the Study ........................................................................................47
5.
STUDY TREATMENT..............................................................................................49

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5.1.
Study Drug Administration.........................................................................................49
5.2.
Dose and Schedule Modifications ..............................................................................49
5.2.1.
Dose Modifications for Nonhematologic Toxicities ..................................................49
5.2.2.
Dose Modifications for Hematologic Toxicities ........................................................52
5.2.3.
Dose Modifications in Case of Induced Drug Liver Injury (Hy’s Law) ....................54
5.3.
Treatment Compliance................................................................................................54
5.4.
Concomitant Medications and Therapies ...................................................................54
5.4.1.
Prohibited Medications and Therapies .......................................................................54
5.4.2.
Concomitant Medications and Therapies Requiring Precautions...............................54
5.4.3.
Drug Interactions ........................................................................................................55
5.5.
Effective Contraception During Study .......................................................................55
5.6.
Study Drug Materials and Management.....................................................................56
5.6.1.
Description of Study Drug..........................................................................................56
5.6.2.
Packaging and Labeling..............................................................................................56
5.6.3.
Storage........................................................................................................................56
5.6.4.
Accountability.............................................................................................................56
6.
STUDY ASSESSMENTS ..........................................................................................58
6.1.
Ophthalmological Examination..................................................................................59
6.2.
Laboratory Assessments.............................................................................................59
6.3.
Considerations during the COVID-19 pandemic .......................................................60
7.
PHARMACOKINETICS ...........................................................................................62
8.
EFFICACY EVALUATIONS....................................................................................63
8.1.
Cohorts A and B .........................................................................................................63
8.1.1.
Efficacy Criteria..........................................................................................................63
8.1.2.
Method of Imaging .....................................................................................................63
8.1.3.
Tumor Definitions ......................................................................................................64
8.1.4.
Response Criteria........................................................................................................65
8.1.4.1.
Target and Non-Target Response Assessments..........................................................65
8.1.4.2.
Additional Criteria to Consider When Making Response Assessments.....................66
8.1.5.
Objective Response Assessment.................................................................................67
8.2.
Cohort C......................................................................................................................68
8.2.1.
Efficacy Criteria..........................................................................................................68

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8.2.2.
Response Criteria........................................................................................................68
8.2.3.
Response Definitions..................................................................................................68
8.3.
Efficacy Endpoints......................................................................................................70
9.
SAFETY EVALUATIONS........................................................................................71
9.1.
Adverse Events...........................................................................................................71
9.2.
Reporting of Adverse Events......................................................................................71
9.2.1.
Terms of Reported Adverse Events............................................................................71
9.2.2.
Severity of Adverse Events ........................................................................................71
9.2.3.
Causal Relationship with Study Drug.........................................................................71
9.2.4.
Outcome of Adverse Events.......................................................................................72
9.2.5.
Follow-up of Adverse Events.....................................................................................72
9.3.
Laboratory Assessments.............................................................................................73
9.3.1.
Reporting and Evaluation of Laboratory Test Results ...............................................73
9.3.2.
Repeat Testing ............................................................................................................73
9.4.
Serious Adverse Events..............................................................................................73
9.4.1.
Definitions of Serious Adverse Events.......................................................................73
9.4.2.
Reporting of Serious Adverse Events (within 24 hours)............................................74
9.4.3.
Reporting of Deaths (within 24 hours).......................................................................74
9.5.
Other Safety Information............................................................................................74
9.5.1.
Pregnancy ...................................................................................................................74
9.5.2.
Overdose.....................................................................................................................75
10.
BIOMARKER EVALUATION .................................................................................76
10.1.
Biomarker Assessments..............................................................................................76
10.1.1.
Objectives and Background........................................................................................76
10.1.2.
Assessment of FGF/FGFR Aberrations in Blood ......................................................76
10.1.3.
Tissue Samples ...........................................................................................................76
10.2.
Sample Storage and Disposal .....................................................................................76
10.3.
Analytical Procedures.................................................................................................76
11.
STATISTICAL CONSIDERATIONS .......................................................................77
11.1.
Estimation of Sample Size..........................................................................................77
11.2.
Timing of Analysis .....................................................................................................78
11.3.
Analysis Populations ..................................................................................................78

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11.4.
Criteria for Handling of Patient Data..........................................................................79
11.5.
Statistical Analyses.....................................................................................................79
11.5.1.
Demographic and Baseline Characteristics ................................................................79
11.5.2.
Study Drug Administration.........................................................................................79
11.5.3.
Efficacy Analyses.......................................................................................................80
11.5.3.1.
Cohorts A and B .........................................................................................................80
11.5.3.2.
Cohort C......................................................................................................................81
11.5.4.
Safety Analyses ..........................................................................................................82
11.5.5.
Pharmacokinetic Analysis ..........................................................................................82
11.5.6.
Pharmacodynamic/Biomarker Analysis .....................................................................82
12.
ADMINISTRATIVE CONSIDERATIONS ..............................................................83
12.1.
Protocol Compliance ..................................................................................................83
12.2.
Protocol Deviations ....................................................................................................83
12.3.
Protocol Amendments ................................................................................................83
12.4.
Study Termination ......................................................................................................83
12.5.
Case Report Forms .....................................................................................................83
12.6.
Access to Source Data/Documents.............................................................................84
12.6.1.
Source Data/Documents .............................................................................................84
12.6.2.
Access to Source Data ................................................................................................84
12.7.
Data Handling.............................................................................................................84
12.8.
Responsibilities of Recordkeeping .............................................................................84
12.8.1.
Investigator and Study Site.........................................................................................84
12.8.2.
Sponsor .......................................................................................................................85
12.9.
Monitoring..................................................................................................................85
12.10.
Financial Disclosure ...................................................................................................85
12.11.
Compensation for Health Injury.................................................................................85
12.12.
Study Administrative Structure ..................................................................................85
13.
QUALITY CONTROL AND QUALITY ASSURANCE .........................................86
13.1.
Quality Control...........................................................................................................86
13.2.
Quality Assurance.......................................................................................................86
14.
ETHICS ......................................................................................................................87
14.1.
Ethical Conduct of the Study......................................................................................87

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14.2.
Documented Informed Consent..................................................................................87
14.3.
Institutional Review Board/Independent Ethics Committee ......................................87
15.
PUBLICATION POLICY ..........................................................................................88
15.1.
Publication Policy.......................................................................................................88
15.2.
Secondary Use of Data ...............................................................................................88
16.
REFERENCES ...........................................................................................................89
APPENDIX A.
ECOG PERFORMANCE..................................................................................92
APPENDIX B.
DIETARY GUIDELINES FOR TREATMENT OF 
HYPERPHOSPHATEMIA ........................................................................................93
APPENDIX C.
CLASSIFICATION OF SUBSTRATES, INHIBITORS, AND 
INDUCERS OF CYP ENZYMES AND TRANSPORTERS ....................................94

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LIST OF TABLES
Table 1: 
Schedule of Events (Cohorts A and B).......................................................................19
Table 2: 
Schedule of Events (Cohort C)...................................................................................21
Table 3:
Schedule of Events – Study Extension Phase: All Cohorts........................................24
Table 4:
Objectives and Endpoints (Cohorts A and B).............................................................38
Table 5:
Objectives and Endpoints: Cohort C ..........................................................................39
Table 6:
Dose Modifications for Related Nonhematologic Toxicities.....................................50
Table 7:
Dose Modifications for Related Ocular Toxicities.....................................................51
Table 8:
Recommendations for Hyperphosphatemia Management..........................................52
Table 9:
Futibatinib Dose Interruption and Modification Criteria for Related 
Hematologic Toxicities for Patients in Cohorts A and B ...........................................53
Table 10:
Pharmacokinetic Blood Sample Collection................................................................62
Table 11:
Target and Non-target Lesions ...................................................................................66
Table 12:
Time Point Response for Patients with Target (±Non-target) Disease.......................67
Table 13:
Time Point Response for Patients with Only Non-target Disease..............................68
Table 14:
Response Definitions for Cohort C.............................................................................69
Table 15:
Observed ORR with Exact 95% Confidence Interval (Cohort A)..............................77
Table 16:
Observed ORR with Exact 95% Confidence Interval (Cohort B)..............................78
Table 17:
Observed CR Rate with Exact 95% Confidence Interval (Cohort C) ........................78
Table 18:
Definitions of Analysis Populations...........................................................................79
LIST OF FIGURES
Figure 1:
Study Schema .............................................................................................................40

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Abbreviation
Definition
AE
Adverse event
AML
Acute myeloid leukemia
ANC
Absolute neutrophil count
ALT
Alanine aminotransferase
ASCO
American Society of Clinical Oncology
AST
Aspartate aminotransferase
BCR
Breakpoint cluster region (gene)
BCRP
Breast cancer resistance protein
CCA
Cholangiocarcinoma
CI
Confidence interval
CR
Complete response
CCyR
Complete cytogenetic response
COVID-19
Coronavirus Disease of 2019
CrCl
Creatinine clearance
CRc
Cytologic complete response per IWG response criteria for AML 
(Cheson et al. 2003)
CRi
Complete response with incomplete hematological recovery
CT
Computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
ctDNA
Circulating tumor DNA
CYP
Cytochrome P450

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Abbreviation
Definition
DCR
Disease control rate
DOR
Duration of response
ECG
Electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
Electronic case report form
EFS
Event-free survival
EMA
European Medicines Agency
EOT
End of treatment/end of therapy
FDA
Food and Drug Administration
FGFR
Fibroblast growth factor receptor
FISH
Fluorescence in situ hybridization
GEJ
Gastro-esophageal junction
GCP
Good Clinical Practice
HSCT
Hematological stem cell transplant
IB
Investigator’s Brochure
iCCA
Intrahepatic cholangiocarcinoma
ICF
Informed consent form
ICH
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use
IEC
Independent Ethics Committee
IND
Investigational New Drug
IRB
Institutional Review Board
IRC
Independent Central Review Committee

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Abbreviation
Definition
MLN
myeloid/lymphoid neoplasms
MPN
Myeloproliferative neoplasms
MRI
Magnetic resonance imaging
NCI
National Cancer Institute
NGS
Next generation sequencing
ORR
Objective response rate
OS
Overall survival
PCyR
Partial cytogenetic response
PD
Progressive disease
PET
Positron emission tomography
PFS
Progression free survival
P-gp
P-glycoprotein
PK
Pharmacokinetic(s)
popPK
Population pharmacokinetics
PR
Partial response
RECIL
Response Evaluation Criteria in Lymphoma
RECIST 1.1
Response Evaluation Criteria in Solid Tumors, Version 1.1
RFS
Relapse-free survival
QD
Once daily
QTcF
QT interval corrected for heart rate using Fridericia’s formula
SAE
Serious adverse event
SAP
Statistical analysis plan
SD
Stable disease

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Abbreviation
Definition
SOP
Standard operating procedure
TEAE
Treatment-emergent adverse event
TOI
Taiho Oncology, Inc.
ULN
Upper limit of normal
WHO
World Health Organization
WOCBP
Women of childbearing potential

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1.
INTRODUCTION
Futibatinib is a novel and selective small molecule irreversible, covalent inhibitor of fibroblast 
growth factor receptor (FGFR) 1–4 that is currently being tested in patient with different cancers. 
Evolving knowledge of the molecular and genetic basis of cancer has led to refinements in the 
categorization of malignancies based on molecular markers. This, in turn, has led to changes in 
study design, specifically tumor agnostic studies that enroll patients with the same genetic 
alterations but not the same histologic or anatomic tumor type. These studies are important 
because they provide insight into the importance of a genomic alteration across various 
histologic tumor types and allow for the development of more targeted therapies (Lacombe et 
al. 2014).
1.1.
Disease Background
FGFR signaling plays a crucial role in cancer cell proliferation, migration, angiogenesis, and 
survival. Recent studies have uncovered increasing evidence that deregulated FGFRs can 
function as driving oncogenes in certain tumor types, maintaining the malignant properties of 
cancer cells (Turner & Grose 2010). When FGFRs are amplified, rearranged, or undergo fusion, 
aberrant activation of downstream pathways results in mitogenic, mesenchymal, and 
antiapoptotic responses in cells. Therefore, FGFRs are attractive targets for therapeutic 
intervention in cancer (Turner & Grose 2010).
FGFR aberrations were found in 7.1% of cancers, with the majority being gene amplifications 
(66%), followed by mutations (26%) and rearrangements (8%) (Helsten et al. 2016).
Although they are rare, FGFR2 fusions with multiple partners have been uncovered in many 
types of cancer, including cholangiocarcinoma (CCA), lung cancer, thyroid cancer, breast 
cancer, and prostate cancer (Wu et al. 2013; Gallo et al. 2015; Yoshihara et al. 2015). Of all the 
FGFRs, FGFR2 shows the broadest range of fusion partners. Fusion genes have also been 
reported in bladder cancer and urothelial carcinoma (Williams et al. 2013; Loriot et al. 2019). It 
is clear that FGFR fusions are emerging as a new class of targetable fusions in solid tumors.
Amplification of FGFR2 has been described in 4-10% of gastric cancer, particularly of the 
aggressive diffuse subtype (Deng et al. 2012; Kunii et al. 2008; Jung et al. 2012; Liu et al. 2014). 
Each year, approximately 990,000 people are diagnosed with gastric cancer worldwide, and 
about 738,000 people die from this disease (Ferlay et al. 2010), making gastric cancer the fourth 
most common cancer and the second most common cause of cancer death (Jemal et al. 2010). 
While the incidence of gastric cancer has been decreasing, the incidence of gastro-esophageal 
junction (GEJ) cancer doubled in Western countries from the 1970s to the 1990s, with rates 
stabilizing today (Buas & Vaughan, 2013).
In vitro, FGFR2-amplified gastric cancer cell lines have been shown to be selectively sensitive to 
the inhibitory effects of FGFR tyrosine kinase inhibitors (Kunii et al. 2008).
Myeloid and lymphoid neoplasms with abnormalities of the FGFR1 gene have been recognized 
as a distinct disease group in the 2008 World Health Organization (WHO) classification of 
hematopoietic neoplasms (Bain et al. 2008). These myeloproliferative neoplasms are 
characterized by eosinophilia, lymphadenopathy, and a high incidence of T-cell non-Hodgkin 

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lymphoma with progression to acute myeloid leukemia (MacDonald et al. 1995). They occur 
over a wide age range of 3 to 84 years, with a median of 44 years, and with a very slight male 
predominance (male to female ratio of 1.2:1) (Jackson et al. 2010). This is a very rare disease, 
with fewer than 100 patients reported around the world (MacDonald et al. 2002; 
Jackson et al. 2010). There is a marked absence of curative treatments for these patients. Of the 
4 FGFRs, FGFR2 and FGFR3 have been identified as having comparatively more frequent gene 
rearrangements (Courjal et al. 1997). However, although hematopoietic neoplasms with FGFR1 
rearrangements are uncommon entities, they are extremely aggressive and resistant to standard 
treatments. One of the most frequently observed cytogenetic abnormalities is t(8;22) 
(p11.2;q11.2). The t(8;22) abnormality results in an in-frame fusion of FGFR1 on 8p11 and the 
breakpoint cluster region (BCR) gene on 22q11. The resultant fusion proteins activate tyrosine 
kinases, which may result in the development of hematologic malignancies 
(Villafuerte-Gutiérrez et al. 2018).
This Phase 2 clinical trial will investigate the efficacy, safety, tolerability, pharmacokinetics 
(PK), and pharmacodynamics of futibatinib in patients with tumors harboring specific FGFR 
aberrations. Patients will be enrolled into one of 3 cohorts: patients with solid tumors harboring 
FGFR rearrangements (excluding primary brain tumors and intrahepatic CCA [iCCA]); patients 
with gastric or GEJ cancer harboring FGFR2 amplification; and patients with myeloid or 
lymphoid neoplasms (MLN) harboring FGFR1 rearrangement.
1.2.
Futibatinib (TAS-120)
1.2.1.
 Clinical Overview
As of 5 September 2019, a total of 460 subjects (41 healthy volunteers and 419 patients) have 
been treated with futibatinib across 4 clinical trials. 

Study 10059010 is an ongoing, Phase 1 study being conducted in Japan to evaluate 
the PK, safety, and preliminary efficacy of futibatinib in patients with advanced solid 
tumors administered futibatinib three times a week (doses 8 to 240 mg) or daily (QD, 
doses 8 to 120 mg). The most frequently reported treatment-emergent AEs (TEAEs) 
(>20% of all patients at all dose levels) were hyperphosphatemia, decreased appetite, 
diarrhea, constipation, nausea, stomatitis, and vomiting. Adverse events were mainly 
Grade 1 or 2.

Study TAS-120-101 is an ongoing, 3-part global study to evaluate the PK, safety, and 
efficacy of futibatinib administered 3 times a week (doses 8 to 200 mg) or QD (doses 
4 to 24 mg): 

Phase 1 Dose Escalation (completed with a total of 86 patients receiving either 
daily or 3-times-per-week dosing)

Phase 1 Dose Expansion, which includes additional cohorts in CCA, gliomas, 
urothelial carcinoma, and basket cohorts with FGF/FGFR aberrations

Phase 2 study initiated in April 2018, evaluating futibatinib at a QD dose of 
20 mg, in patients with iCCA harboring FGFR2 gene rearrangements 

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
The most frequently reported TEAEs (>20%) in patients administered futibatinib 
20 mg QD (recommended Phase 2 dose) were hyperphosphatemia, diarrhea, 
constipation, nausea, dry mouth, increased ALT, increased AST, and fatigue.

Study 10059020, a Phase 1, PK, and bioequivalence study in healthy adult males. 
This completed study compared two futibatinib formulations and found them to be 
biologically equivalent. 

Study TAS-120-102, a food effect study in healthy adult subjects. This completed 
study evaluated the effect of food on the PK of futibatinib under fasting or fed 
conditions and demonstrated that PK was affected by the consumption of a high-fat, 
high-calorie meal.  
Efficacy has been observed in different tumor types:

Solid tumors harboring FGFR rearrangements, including iCCA, head and neck, 
unknown primary, and gastric cancer

Gastric cancer with FGFR2 amplification

MPN with FGFR1 rearrangement

Other solid tumors with different FGFR aberrations
Refer to the current Investigator’s Brochure (IB) for more detailed background information on 
futibatinib.
1.3.
Summary of Study Rationale
Based on available preclinical and clinical data to date, the Sponsor concludes that the 
benefit-risk assessment results of futibatinib support the continued enrollment and treatment of 
patients in clinical trials and supports further investigation of futibatinib in tumors with FGFR 
aberrations.
The Phase 2 study described in this protocol will evaluate the efficacy and safety of futibatinib in 
patients with FGFR aberrations in 3 distinct cohorts.
Based on prior safety and efficacy experience in the broad Phase 1 dose escalation and expansion 
study, a dose of 20 mg QD of futibatinib has been selected for use in this Phase 2 study. The 
study drug is administered continuously without interruption. Treatment cycles of 28 days will 
be used to define the protocol specified interval for tumor measurement and other interventions.

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2.
OBJECTIVES AND ENDPOINTS
The objectives and endpoints of this study are shown in Table 4 and Table 5. 
Table 4:Objectives and Endpoints (Cohorts A and B)
Primary
To evaluate the objective response rate (ORR) 
in patients with solid tumors harboring FGFR 
rearrangements or gastric cancer (including 
GEJ cancer) harboring FGFR2 amplifications 
based on independent central review of 
radiologic images (IRC)
ORR, defined as the proportion of patients experiencing a best 
overall response of partial response (PR) or complete response 
(CR) (per Response Evaluation Criteria in Solid Tumors, 
Version 1.1 [RECIST 1.1]), based on IRC 
Secondary 
Key secondary:

To evaluate duration of response (DOR) 
based on IRC 
Additional secondary:

To evaluate ORR based on Investigator 
assessment 

To evaluate progression-free survival 
(PFS), disease control rate (DCR), and 
overall survival (OS)

To assess safety and tolerability

DOR defined as the time from the first documentation of 
response (CR or PR per RECIST 1.1 based on IRC) to the 
first documentation of objective tumor progression or death 
due to any cause, whichever occurs first, based on IRC

ORR, defined as the proportion of patients experiencing a 
best overall response of partial response of PR or CR (per 
RECIST 1.1), based on Investigator assessment

DCR, defined as the proportion of patients experiencing a 
best overall response of stable disease (SD), PR, or CR (per 
RECIST 1.1), based on IRC 

PFS, defined as the time from first dose of study drug to the 
date of death (any cause) or disease progression (based on 
IRC), whichever occurs first

OS, defined as the time from the date of first dose to the 
death date

Safety based on reported AEs and on-study laboratory 
parameters, graded according to the National Cancer 
Institute—Common Terminology Criteria for Adverse 
Events, Version 5.0 (NCI-CTCAE V5.0), 
Exploratory 

To assess the possible impact of genetic 
alterations or other laboratory 
abnormalities on the efficacy of 
futibatinib 

To assess the population 
pharmacokinetics (popPK) and exposure 
response

Assessment of genetic alterations in circulating tumor DNA 
(ctDNA), tumor biopsy, and/or plasma samples, and their 
possible correlation with clinical outcome.

PK data will be pooled with data from other cohorts or other 
studies for a popPK analysis.

The relationship between popPK model derived exposure 
and response will be explored

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Table 5:Objectives and Endpoints: Cohort C
Overall Objective
The overall objective of Cohort C is to assess the clinical activity of futibatinib as monotherapy in the treatment of 
patients with MLN harboring FGFR1 rearrangements.
Primary
To evaluate complete response (CR) rate 
CR rate, defined as the proportion of patients who achieved a CR.
Secondary 

To evaluate:
o
ORR
o
CR + complete response with 
incomplete hematological recovery 
(CRi) rate 
o
Complete or partial cytogenetic 
responses (CCyR or PCyR) rate
o
Duration of CR
o
Duration of CR+CRi
o
DOR
o
Time-to-events 

To assess the safety and tolerability

ORR, defined as the proportion of patients who achieved a 
CR, CRi, or PR

CR+CRi rate, defined as the proportion of patients who 
achieved a CR or CRi 

CCyR rate, defined as the proportion of patients who 
achieved CCyR

PCyR rate, defined as the proportion of patients who achieved 
PCyR

Duration of CR defined as the time from the first 
documentation of CR to the first documentation of objective 
tumor progression or death due to any cause, whichever 
occurs first

Duration of CR+CRi defined as the time from the first 
documentation of CR/CRi to the first documentation of 
objective tumor progression or death due to any cause, 
whichever occurs first

DOR defined as the time from the first documentation of CR, 
CRi, or PR to the first documentation of objective tumor 
progression or death due to any cause, whichever occurs first 

PFS, defined as the time from first dose of study drug to the 
date of death (any cause) or disease progression, whichever 
occurs first

Relapse-free survival (RFS), defined as the time from the first 
documentation of CR to the first documentation of disease 
relapse or death due to any cause, whichever occurs first. 

Event-free survival (EFS) (leukemia presentation only), 
defined as the time from first dose of study drug to treatment 
failure, disease relapse after CR, or patient death from any 
cause. 

OS, defined as the time from the date of first dose to the death 
date. 

Safety based on reported AEs and on-study laboratory 
parameters, graded according to the NCI-CTCAE V5.0.
Exploratory

To assess the pharmacodynamic effects of 
treatment with futibatinib

To assess the association of response and 
mechanisms of resistance in tumor tissue 
biopsies and/or blood

To assess the popPK and exposure 
response

Changes in pharmacodynamic markers assessed in bone 
marrow tissue biopsies.

Exploratory association of tissue and/or blood markers with 
tumor efficacy endpoints and/or tumor resistance to 
futibatinib.

PK data will be pooled with data from other cohorts or other 
studies for a popPK analysis.

The relationship between popPK model derived exposure and 
response will be explored.

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3.
INVESTIGATIONAL PLAN
3.1.
Overview of Study Design
Study TAS-120-202 is an open-label, multinational, 3-arm, Phase 2 study evaluating the 
efficacy, safety, tolerability, PK, and pharmacodynamics of futibatinib in patients with FGFR 
aberrations. Eligible patients will be assigned to 1 of 3 treatment cohorts based on diagnosis and 
FGFR gene aberration status (Figure 1):
Figure 1:
Study Schema
Patients will receive futibatinib at an oral dose of 20 mg once a day on a continuous 28-day 
cycle. 
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, response assessments should be continued until 
disease progression is documented or until initiation of subsequent new anticancer therapy 
(whichever occurs first). 

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Patients will be followed for survival every 12 weeks (±2 weeks) until survival events (deaths) 
have been reported for at least 75% of enrolled patients in each Cohort, the patient withdraws 
consent, or the study is terminated early by the Sponsor.
Additional cohorts may be added in the future in case of new emerging data. This change will be 
implemented through a protocol amendment which will describe the rationale for the addition(s).
3.2.
Scientific Rationale for Study Design
Please see Section 1.3.
3.3.
Study Periods and Visits for Each Patient
The study periods / visits described in this section are defined for all patients. Please see the 
schedule of events for an outline of all assessments to be performed during each study period / 
visit.
For all patients, the Safety Assessment Period begins at the time informed consent has been 
documented and continues until at least 30 days after the last dose of futibatinib. After the 
30-day Safety Follow-Up Visit (see below), patients who have not started treatment with a new 
anticancer therapy will be assessed for drug-related serious adverse events (SAEs) only.
For each patient, the Study Duration is defined as the time informed consent has been 
documented to the last day of Disease Assessment Follow-up / Survival Follow-up (see below).
3.3.1.
Screening Period
The Screening Period is defined as the time informed consent has been documented to when they 
receive the first dose of futibatinib. Determination of eligibility is based on the entry criteria 
enumerated in Section 4. No protocol-specific procedures or assessments may be performed 
prior to documented consent, except for procedures that represent standard-of-care.
3.3.2.
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 first dose of futibatinib (Day 1) to the date of last dose of futibatinib. An 
end-of-treatment (EOT) visit must be performed within 7 days after the decision is made to 
discontinue futibatinib; at this visit, every effort should be made to perform the assessments 
outlined in the schedule of events. 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.
3.3.3.
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 drug through the 
30-Day Safety Follow-Up Visit, which must be performed 30 days (+7 days) following the last 
dose of study drug. If the patient starts new anticancer therapy within 30 days of the last dose of 
study drug, 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 the 
schedule of events. If the patient is unable to return to the study site, a follow-up phone call can 

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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 Follow-Up Visit (see below), patients who have not started treatment 
with a new anticancer therapy will be assessed for drug-related SAEs only.
3.3.4.
Post-Discontinuation Considerations
Patients who discontinue without documented disease progression should continue to undergo 
response assessments according to the Schedule of Events (that is, every 8 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).
3.3.5.
Survival Follow-Up
Once a patient discontinues study treatment, regardless of the reason, Survival Follow-Up will 
begin, unless the patient withdraws consent or the study is terminated early by the Sponsor. 
During this period, the patient or family should be contacted for Survival Follow-Up every 
12 weeks (±2 weeks) until survival events (deaths) have been reported for 75% of enrolled 
patients, patient withdraws consent or the study is terminated early by the Sponsor. In addition, 
all subsequent anticancer treatments will be recorded.
3.4.
Study Completion and Study Extension
The study will be considered complete when:

Survival events (deaths) have been reported for at least 75% of enrolled patients in 
either Cohort A, B, or C, whichever comes last; or

The study is halted early for any reason.
Following Study Completion, patients deriving benefit from study drug in the opinion of the 
Investigator and Sponsor may be permitted to continue treatment with futibatinib in a Study 
Extension phase. The Sponsor will inform study sites when a Study Extention phase is initiated. 
During Study Extension, patients may receive treatment until withdrawal criteria are met and 
study drug is available.  
All safety assessments are to be continued according to the Study Extension phase schedule 
(Table 3). Specifically, study extension data collection is to include, at a minimum:

Study drug administration

Study drug accountability

Serious adverse events

Non-serious AEs that are related to study drug or result in treatment discontinuation

Any cases of pregnancy or overdose

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3.5.
Patient Enrollment
Eligibility must be verified prior to patient enrollment. Patients will be enrolled via an Interactive 
Voice/Web Response System (IXRS). The patient should receive the first dose of study drug 
within 3 days following enrollment. 
3.6.
End of Trial
The end of the trial will occur when all patients (including patients in the Study Extension phase, 
if any) have discontinued treatment and undergone all protocol-mandated assessments (including 
the 30-Day Safety Follow-Up Visit).

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4.
SELECTION AND WITHDRAWAL OF PATIENTS
Results of FGFR gene aberration status should be available before the patient undergoes any 
protocol-specific procedures. 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 participation in this 
study:
1. Provide documented informed consent (refer to Section 6.3)
2. ≥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. Has recovered from the acute toxic effects of prior anticancer therapy to baseline or 
Grade 1 (except toxicities which are not clinically significant such as alopecia)
5. Known FGFR aberration status and tumor type that meet all of the criteria for one of the 
following cohorts: 
a. Cohort A
i.
Histologically confirmed, locally advanced, advanced, or metastatic solid 
tumors harboring a FGFR1-4 rearrangement determined in tumor tissue using 
next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), 
or other assays that can determine gene rearrangements in tumor tissues. 
Patients with primary brain tumor or iCCA are not eligible.
ii. Measurable disease per RECIST 1.1 
iii. Had disease progression/recurrence after standard treatment for their advanced 
or metastatic cancer 
b. Cohort B
i.
Histologically confirmed, locally advanced, advanced, or metastatic gastric or 
GEJ adenocarcinoma harboring a FGFR2 amplification. The tumor must have 
an FGFR2/CEN10 ratio of ≥5 or an FGFR2 copy number ≥10 signals per cell 
determined in tumor tissue using NGS, FISH, or other assays that can 
determine gene amplifications in tumor tissues.
ii. Measurable disease per RECIST 1.1
iii. Received at least 2 prior systemic regimens for advanced/metastatic disease
iv. Experienced disease progression/recurrence during or after the most recent 
prior systemic treatment for advanced/metastatic gastric or GEJ cancer. 
c.
Cohort C
i.
Confirmed MLN with a FGFR1 rearrangement as defined by WHO criteria 
ii. Not a candidate for hematological stem cell transplant (HSCT) or relapsed 
after HSCT and donor lymphocyte infusion, and progressed and not a 
candidate for other therapies. 
6. Has archival or fresh tumor tissue (preferably in block format) for Cohorts A and B and 
bone marrow tissue for Cohort C available to send to central laboratory.

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7. Adequate organ function as defined by the following criteria:
a. Cohorts A and B:
i.
Absolute neutrophil count (ANC) ≥1.0 × 109/L
ii. Platelet count ≥75,000/mm3 (≥75 × 109/L) 
iii. Hemoglobin ≥9.0 g/dL
iv. ALT and aspartate aminotransferase (AST) ≤ 3.0 × upper limit of normal 
(ULN); if liver function abnormalities are due to underlying liver metastasis, 
AST and ALT ≤5.0 × ULN.
v. Total bilirubin ≤1.5 × ULN, or ≤3.0 × ULN for patients with Gilbert’s 
syndrome.
vi. Creatinine clearance (CrCl) (calculated or measured value): ≥40 mL/min. For 
calculated CrCl, use the Cockcroft-Gault formula (Section 6).
vii. Phosphorus <1.5 ULN
b. Cohort C
i.
ALT and AST ≤3.0 × ULN; if liver function abnormalities are due to 
underlying liver metastasis, AST and ALT ≤5.0 × ULN.
ii. Total bilirubin ≤1.5 × ULN, or ≤3.0 × ULN for patients with Gilbert’s 
syndrome.
iii. CrCl (calculated or measured value): ≥40 mL/min. For calculated CrCl, use 
the Cockcroft-Gault formula (Section 6).
iv. Phosphorus <1.5 ULN
8. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test 
prior to administration of the first dose of futibatinib. Female patients are not considered 
to be of child-bearing potential if they are post-menopausal (no menses for 12 months 
without an alternative medical cause) or permanently sterile (hysterectomy, bilateral 
salpingectomy, or bilateral oophorectomy).
9. 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 or longer based 
on local requirements.
10. Ability to take medications orally (feeding tube is not permitted).
11. 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 participation in 
this study:
1. Currently receiving an investigational drug in a clinical trial or participating in any other 
type of medical research judged not to be scientifically or medically compatible with this 
study. If a patient is currently enrolled in a clinical trial involving non-approved use of a 
device, then agreement with the Investigator and the Sponsor’s Medical monitor is 
required to establish eligibility.

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2. 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.
3. 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.
4. Treatment with any of the following within the specified time frame prior to the first dose 
of futibatinib:
a.
Major surgery within 4 weeks (surgical incision should be fully healed)
b. Radiotherapy for extended field within 4 weeks or limited field radiotherapy within 
2 weeks
c.
A drug that has not received regulatory approval for any indication within 14 or 
21 days of treatment for a nonmyelosuppressive or myelosuppressive agent, 
respectively
5. Received strong inhibitors or inducers of CYP3A4 within 2 weeks
6. Prior treatment with an FGFR inhibitor
7. 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 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 
futibatinib administration, or may interfere with the interpretation of study results, 
and in the judgment of the Investigator would make the patient inappropriate for entry 
into this study
8. Active central nervous system (CNS) metastasis and/or carcinomatous meningitis. 
Patients with previously treated brain metastases that are clinically and radiologically 
stable (for at least 4 weeks prior to enrollment) are eligible.

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9. Known additional malignancy that is progressing or has required active treatment within 
the past 2 years. Patients with basal cell carcinoma of the skin, squamous cell carcinoma 
of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have 
undergone potentially curative therapy are not excluded.
10. Pregnant or breastfeeding.
4.3.
Screen Failure 
Screen failures are defined as patients who consent to participate in 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 respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility criteria, 
and any SAE 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 3 times. Rescreened patients should be assigned the same patient 
identification code as for the initial screening.
4.4.
Discontinuation of Treatment
A patient will be discontinued from all study drug for any of the following reasons: 
1. Disease progression 
2. 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 2 dose reductions outlined in this protocol
3. 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
4. Pregnancy
5. Termination of the study by the Sponsor 
6. At the patient’s request at any time irrespective of the reason 
Patients who withdraw consent for further treatment 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 assessments, the patient should be considered to have discontinued the 
study as described in Section 4.5.
4.5.
Withdrawal from the Study
A patient will be withdrawn from all study interventions and assessments (that is, discontinued 
from the study without follow-up) for any of the following reasons: 
1. Death
2. Lost to follow-up

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
A patient will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.

The following actions must be taken if a patient fails to return to the clinic for a 
required study visit:

The site must attempt to contact the patient and reschedule the missed visit as 
soon as possible and counsel the patient on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the patient wishes to and/or 
should continue in the study.

Before a patient is deemed lost to follow-up, the Investigator or designee must 
make every effort to regain contact with the patient (where possible, 3 telephone 
calls and, if necessary, a certified letter to the patient’s last known mailing address 
or local equivalent methods). These contact attempts should be documented in the 
patient’s medical record.

Should the patient continue to be unreachable, they will be considered to have 
withdrawn from the study.
3.  Patient withdrawal of consent to further follow-up assessments, irrespective of the 
reason.

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5.
STUDY TREATMENT
5.1.
Study Drug Administration
A study cycle is defined as 28 days. Futibatinib is supplied as 4 mg tablets and will be taken 
orally at a dose of 20 mg daily until the patient meets any of the administration discontinuation 
criteria (see Section 4.4).
Futibatinib should be administered under fasting conditions. It should be taken with a glass of 
water, on an empty stomach, at the same time each day. No food should be consumed for 2 hours 
prior and 1 hour after the dose of futibatinib, but patients may drink water during this period.
When a PK sample is collected, futibatinib should be administered on site after collection of the 
first PK sample.
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. 
5.2.
Dose and Schedule Modifications 
Stepwise dose reductions of 4 mg to 16 mg (first reduction) and 12 mg (second reduction) are 
permitted based on toxicities. If dose reduction fails to result in achieving the minimal criteria to 
resume treatment or, if toxicities occur which would necessitate reduction of the dose of 
futibatinib below 12 mg QD, the patient should be discontinued from futibatinib. 
Following a dose reduction, if a benefit/risk assessment favors an increase of futibatinib dose up 
to the initial starting dose (20 mg QD), an agreement with the Sponsor’s Medical monitor is 
required prior to the dose increase. 
If toxicities related to the dose reduction do not recover based on the criteria defined below 
within 28 days after the last dose of futibatinib, the patient will be discontinued permanently 
from treatment (Section 4.4). If resumption criteria are met within 28 days of the last dose of 
futibatinib, the patient may resume futibatinib treatment at the appropriate dose level.
5.2.1.
Dose Modifications for Nonhematologic Toxicities
Dosing modification guidelines for nonhematologic and ocular toxicities are provided in Table 6 
and Table 7, respectively.
Recommendations for hyperphosphatemia management are provided in Table 8. These are 
suggested guidelines based on emerging data from studies evaluating FGFR inhibitors and 
studies of futibatinib (Appendix B).

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Table 6:
Dose Modifications for Related Nonhematologic Toxicities
Gradea
Dose 
Interruption/Resumption
Dose Adjustment
Grade 1 or 2
Maintain treatment at the same 
dose level
None
Grade 3
Withhold treatment until 
return to baseline or Grade ≤1
Reduce by 1 dose level from the previous level.
For Grade 3 nausea, vomiting, and/or diarrhea lasting 
>72 hours despite optimal medical management require 
withhold of treatment and dose reduction by one level.
Grade 4 
Discontinue treatment 
Permanent discontinuation of futibatinib.
Grade 4 (lab 
abnormality AE)
Withhold treatment until 
return to baseline or Grade ≤1
Futibatinib 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, 
futibatinib should first be held until toxicity returns to 
baseline or Grade ≤1.
Abbreviations: AE=adverse event; ALT=alanine aminotransferase; AST=aspartate aminotransferase. 
a Interrupt futibatinib if any toxicities are intolerable, regardless of the grade (including Grade 1 and 2). If or when the toxicity 
resolves to a tolerable state, consideration can be given to resuming futibatinib at the same dose if deemed appropriate or 
reduced by one dose level if needed.

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Table 7:
Dose Modifications for Related Ocular Toxicities
Grade and Definition
Study Drug Managementa
Grade 1
If there is no evidence of ocular toxicity on ophthalmologic examination, continue 
futibatinib therapy at the same dose level.
If diagnosis from ophthalmologic examination is keratitis or retinal abnormality 
such as central serous retinopathy (CSR)/ retinal pigment epithelial detachments 
(RPED), withhold futibatinib until signs and symptoms have resolved.
If toxicity is reversible (complete resolution or stabilization and asymptomatic) in 
4 weeks according to ophthalmologic examination, resume futibatinib therapy at 
the next lower dose level after consultation with the Sponsor’s Medical monitor.
Monitor for recurrence every 1 to 2 weeks for a month and as clinically 
appropriate thereafter. If there is no recurrence then re-escalation can be 
considered in consultation with the Sponsor’s Medical monitor.
Grade 2 
Withhold futibatinib therapy.
If there is no evidence of drug-related corneal or retinal pathology on 
ophthalmologic examination, withhold futibatinib until signs and symptoms have 
resolved. Resume futibatinib therapy at the next lower dose level.
If diagnosis from ophthalmologic examination is keratitis or retinal abnormality, 
withhold futibatinib until signs and symptoms have resolved or stabilized.
If toxicity is Grade 2 and reversible (complete resolution or stabilization and 
asymptomatic) within 4 weeks according to ophthalmologic examination, resume 
futibatinib therapy at the next lower dose level after consultation with the 
Sponsor’s Medical monitor.
Monitor for recurrence every 1 to 2 weeks for a month and as clinically 
appropriate thereafter. If there is no recurrence then re-escalation can be 
considered in consultation with the Sponsor’s Medical monitor.
Grade 3 
If the toxicity is Grade 3, report as an SAE and consider permanent discontinuation 
of futibatinib. If the toxicity is Grade 3 and reversible (complete resolution or 
stabilization and asymptomatic) within 4 weeks and the patient is receiving clinical 
benefit, and the Investigator and the Sponsor’s Medical monitor agree that re-
starting drug is in the best interest of the patient, then futibatinib therapy may be 
resumed at 2 dose levels lower if appropriate. Monitor for recurrence using 
appropriate investigations every 1 to 2 weeks for a month and as clinically 
appropriate thereafter.
For cases of recurrence, consider permanent discontinuation.
Grade 4
Permanently discontinue treatment with futibatinib.
Report as an SAE and monitor resolution of the event until complete resolution, 
stabilization, or the patient is lost to follow-up or withdraws consent (whichever 
happens first).
a If a patient has been deriving benefit from treatment, and the Investigator can demonstrate that reintroduction of study drug is in 
the best interest of the patient considering the terminal nature of the disease, the drug may be reintroduced at a lower dose 
and/or intensity if the Sponsor’s Medical monitor is in agreement with this assessment. With appropriate re-consenting, the 
patient can be re-treated with a 1- or 2-dose level reduction as appropriate, along with appropriate clinical follow-up as 
designated by the Investigator. The Investigator should also have the patient re-consent, explaining that reintroduction of study 
drug could lead to increased risk of recurrence.

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Table 8:
Recommendations for Hyperphosphatemia Management
Serum Phosphorus Resulta
(mg/dL and mmol/L)b 
Futibatinib Dose Interruption and Modificationc, d, e, f
Recommended Phosphate Binder for Management of Hyperphosphatemiaf
ULN < P <5.5 (mg/dL) 
ULN < P <1.78 (mmol/L)
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]. 
Reassess serum phosphate within 7 days.
5.5 ≤ P ≤7.0 (mg/dL) 
1.78 ≤ P ≤2.26 (mmol/L) 
No interruption, implement phosphate binder (monotherapy or in combination). 
Start with Sevelamer monotherapy (range from 800 mg TID to 2400 mg TID). 
Reassess serum phosphate within 7 days. 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 titration,c if phosphate level continues to increase. 
7.0 < P ≤10.0 (mg/dL) 
2.26< P ≤3.23 (mmol/L)
Dose reduce futibatinib to the next lower dose level and intensify 
phosphate-lowering therapy.
Reassess serum phosphate within 7 days and at least once a week. 
If the serum phosphorus level has resolved to ≤5.5 mg/dL/1.78 mmol/L within 
14 days after dose reduction, continue futibatinib at the reduced dose level. 
If the serum phosphorus level has not resolved to ≤5.5 mg/dL/1.78 mmol/L after 
14 days, further reduce futibatinib from the last reduced dose level (or no lower 
than 12 mg QD).
If the serum phosphorus level has not resolved to ≤5.5 mg/dL/1.78 mmol/L after 
14 days of the second dose reduction of futibatinib (or no lower than 12 mg QD), 
interrupt dosing with futibatinib until it is resolved to ≤5.5 mg/dL/1.78 mmol/L 
before resuming futibatinib at the reduced dose prior to dose interruption.
P >10.0 (mg/dL) 
P >3.23 (mmol/L) 
Interrupt futibatinib until serum phosphate has resolved to ≤5.5 mg/dL/1.78 
mmol/L, then resume futibatinib at the next lower dose level and intensify 
phosphate-lowering therapy.
Reassess serum phosphate within 7 days and at least once a week. If after 2 dose 
interruptions and 2 dose reductions the serum phosphorus level has not resolved to 
≤5.5 mg/dL/1.78 mmol/L after 14 days, permanently discontinue futibatinib. 
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 x 0.3229 (conversion factor).
c Interrupt futibatinib if any toxicities are intolerable. If or when the toxicity resolves to a tolerable state, consideration can be 
given to resuming futibatinib at the same dose if deemed appropriate or reduced by one dose level if needed.
d Serum calcium levels should be assessed at the same time.
e Futibatinib will be permanently discontinued if ectopic mineralization or calcification associated with hyperphosphatemia and 
considered clinically significant are observed.
f 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.
g Titrate the dose every 2-3 weeks until an acceptable serum phosphate level is reached.
5.2.2.
Dose Modifications for Hematologic Toxicities
Criteria for dose interruption and resumption for hematologic toxicities for patients in Cohorts A 
and B are presented in Table 9. For patients in Cohort C, dose modifications will be made at the 
Investigator’s discretion.

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Table 9:
Futibatinib Dose Interruption and Modification Criteria for Related Hematologic 
Toxicities for Patients in Cohorts A and B
CTCAE Grade (value) 
Recommended dose modification any time during a cycle of 
futibatiniba
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 with 
a single temperature of ≥38.3°C [101°F] or 
a sustained temperature of ≥38° C 
[100.4°F]) 
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
a  Interrupt futibatinib if any toxicities are intolerable, regardless of the grade (including Grade 1 and 2). If or when 
the toxicity resolves to a tolerable state, consideration can be given to resuming futibatinib at the same dose if 
deemed appropriate or reduced by one dose level if needed.

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5.2.3.
Dose Modifications in Case of Induced Drug Liver Injury (Hy’s Law)
Futibatinib will be permanently discontinued if liver function test abnormalities fulfill Hy’s Law 
criteria defined as:
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, liver metastases, or another 
drug capable of causing the observed liver injury):

Elevated aminotransferase enzymes of >3 x ULN

Alkaline phosphatase (ALP) <2 x ULN

Associated with an increase in bilirubin ≥2 x ULN
5.3.
Treatment Compliance
Each patient will be instructed to comply with the dosing regimen of futibatinib.
Compliance with all study drug administration should be documented in the patient’s source 
documents (Section 5.6.3).
5.4.
Concomitant Medications and Therapies
5.4.1.
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’s Medical monitor, it can be administered, but the patient will be 
censored for the primary endpoint analysis.
5.4.2.
Concomitant Medications and Therapies Requiring Precautions 
Supportive treatment is allowed based on available institutional or local guidelines.
Local or regional palliative cryotherapy or radiation, such as for bone pain or palliative surgery 
(non-antineoplastic intent), are permitted (provided the target lesion is not a site of measurable 
disease and is not indicative of disease progression). Study drug should be ceased a minimum of 
2 days prior to administration of palliative treatment, and may be resumed 7 days after the 
procedure or when the patient has recovered from the side effects of the procedure.
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 American Society of Clinical Oncology (ASCO) guidelines 
(Smith et al. 2015). 

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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).
5.4.3.
Drug Interactions
The following information is based on results from in vitro studies and clinical pharmacology 
studies of drug interactions in humans. Futibatinib is a substrate of CYP3A and 
moderate-to-strong inhibitors or inducers of CYP3A have potential clinical drug-drug 
interactions with futibatinib. Caution is advised if these drugs are given concomitantly (see 
Appendix C , Classification of Substrates, Inhibitors, and Inducers of CYP Enzymes and 
Transporters). 
Moderate and strong CYP3A inducers: The results of Study TAS-120-103 showed a strong 
CYP3A inducer decreased futibatinib AUC by approximately 64%. A moderate CYP3A inducer 
was predicted to decrease futibatinib AUC by approximately 48%.
Moderate and strong CYP3A inhibitors: The results of Study TAS-120-103 showed a strong 
CYP3A inhibitor increased futibatinib AUC by approximately 41%. A moderate CYP3A 
inhibitor was predicted to increase futibatinib AUC by approximately 20% to 40%.
Strong CYP3A inhibitors and inducers (see Appendix C) should be avoided or substituted with 
other concomitant therapies while receiving futibatinib, if possible. However, if concomitant use 
with a strong CYP3A inhibitor cannot be avoided, futibatinib dose reductions should be 
considered by the investigator, considering the patient's individual benefit/risk and discussed 
with the Sponsor. The patient should be closely monitored for any AEs. Please see Section 5.2 
for recommended dose modifications.
Additionally, in vitro studies have shown potential drug-drug interactions may occur with 
concomitant use of futibatinib and those drugs that are P-gp or BCRP substrates/inducers. 
Futibatinib is a potential inhibitor of P-gp and BCRP, and a substrate of P-gp and BCRP in vitro. 
Futibatinib may alter the PK of P-gp and BCRP substrates. P-gp and BCRP inhibitors may affect 
the PK of futibatinib. Caution is advised if these drugs are given concomitantly.
5.5.
Effective Contraception During Study
Female patients considered not to be of child-bearing 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 patients and partners of male patients, effective contraception is 
required during the study and for 90 days after the last dose of study drug, or longer if necessary 
based on local requirements. Effective contraception is defined as follows:

Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation:

Oral

Intravaginal

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
Transdermal

Progestogen-only hormonal contraception associated with inhibition of ovulation:

Oral

Injectable

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 
method) 
Male patients, unless sterile (vasectomy with post-procedure semen analysis), with partners who 
are WOCBP should use a male condom in combination with at least one of the effective 
contraception methods during the study and for 90 days or longer based on local requirements 
after the last dose of study drug. Donation of sperm or ova is not allowed during the study and 
for 90 days or longer based on local requirements following the last dose of study drug.
5.6.
Study Drug Materials and Management
Futibatinib will be supplied by the Sponsor. Detailed information such as the requirements for 
accountability and disposal of study drug can be found in the Pharmacy Manual, which will be 
provided separately.
5.6.1.
Description of Study Drug
Futibatinib will be provided as 4-mg tablets for oral use. Please refer to the IB for additional 
information.
5.6.2.
Packaging and Labeling
Futibatinib will be packaged and labelled according to local laws and regulations.
5.6.3.
Storage
Futibatinib tablets should be stored in accordance with the label.
5.6.4.
Accountability
The Investigator is responsible for ensuring that all study drug received at the site is inventoried 
and accounted for throughout the study. All study drugs will be stored and disposed of according 
to the Sponsor's instructions. The dispensing of study drug to the patient and the return of study 
drug from the patient must be documented in the patient’s source documents. The patient will be 
provided a diary to record when they have taken the study drug each day. Patients must be 
instructed to return all original containers, whether empty or containing study drug. 

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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.

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6.
STUDY ASSESSMENTS
The Schedule of Events (Table 1 for Cohorts A and B, Table 2 for Cohort C, and Table 3 for 
Extension Phase) summarizes the frequency and timing of all applicable study assessments, 
including allowable windows for study visits and assessments / procedures. Documented 
informed consent must be provided before any study-related procedures are performed.
Any AEs directly associated with a screening procedure should be reported as described in 
Section 9.2. 
Assessment
Details
Review of inclusion/exclusion 
criteria
See Section 4.1 and 4.2.
Eligibility must be confirmed prior to first dose of study drug. 
Demographics/medial history
Sex, age, clinical diagnosis, date and method of diagnosis, prior cancer therapy, 
relevant medical history (past and concurrent)
Baseline signs and symptoms
Signs and symptoms occurred after informed consent has been documented but 
before administration of first dose of futibatinib.
Physical examination
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.
12-lead electrocardiogram
Single, resting, semirecumbent 12-lead electrocardiogram 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 electrocardiogram data.
Hematology
Red blood cell count, hemoglobin, hematocrit, platelets, white blood cell count 
with differential, neutrophils (ANC), lymphocytes, monocytes, eosinophils, 
basophils
Serum chemistry
AST, ALT, alkaline phosphatase, total bilirubin, direct bilirubin, albumin, lactate 
dehydrogenase, inorganic phosphorus, triglyceride, total cholesterol, creatinine, 
urea or blood urea nitrogen, sodium, potassium, chloride, calcium (corrected 
value), magnesium, blood glucose, uric acid 
For a calculated creatinine clearance (CrCl) value, use the Cockcroft-Gault 
formula:
Male CrCl (mL/min) = Body wt (kg)×(140-age)[72×serum creatinine (mg/dL)]
Female CrCl (mL/min) = male CrCl×0.85
Coagulation
Prothrombin time-international normalized ratio, activated partial thromboplastin 
time, fibrinogen
Pregnancy test
Serum β human chorionic gonadotrophin (human chorionic stimulating hormone) 
test required for WOCBP
Ophthalmological examination
See Section 6.1 
PK blood sampling
See Section 7. 

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Assessment
Details
Pharmacodynamic biomarker 
blood sampling
See Section 10 
Efficacy assessments
See Section 8. 
Concomitant 
medication/concomitant 
therapy
Including all medications / therapies administered from the time informed 
consent has been documented through 30 days after administration of the last 
dose of study drug or until the start of new anticancer therapy.
AE monitoring
All AEs will be collected from the time informed consent has been documented 
until Safety Follow-Up Visit is completed after the last dose of any study drug 
(safety follow-up) or until the start of new anticancer therapy, whichever is 
earlier. See Section 9.
Abbreviations: AE=adverse event; ALT=alanine aminotransferase; ANC=absolute neutrophil count; AST=aspartate 
aminotransferase; CrCl=calculated creatinine clearance; ICF=informed consent form; QT = QT interval; QTcF = Fridericia's 
Correction Formula; RR=intra-beat; WOCBP=women of childbearing potential
6.1.
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 by an ophthalmologist or qualified delegate at 
screening and 4-6 weeks after first dose; additional on-study evaluation as needed due to 
physician judgment and/or symptoms or signs of mineral deposits.  
Each evaluation will encompass: 

External ocular examination

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)

Dilation of the pupil with direct/indirect fundoscopy per institutional guidelines and 
local clinical practice
6.2.
Laboratory Assessments 
All laboratory assessments will be performed locally. The laboratory must provide normal 
reference ranges for hematology, chemistry, and coagulation tests. If justified (eg, deterioration 
of the patient’s health conditions and/or distance from the clinical site) and allowed by the 
country and institution, laboratory tests performed by external laboratories may be used for the 
study. However, laboratory reference ranges and accreditation are required. All laboratory test 
results (internal or external) must be reviewed for clinical significance by the Investigator. 
Any clinically significant events must be followed and reported as required by the protocol 
(please see Section 9.3.1).

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6.3.
Considerations during the COVID-19 pandemic
During the COVID-19 pandemic, patients will be enrolled at the Investigator’s discretion 
considering patient’s benefit and risk and the availability of staff at the study sites. The Sponsor 
will perform a risk assessment of the study on an ongoing basis and prioritize patient safety to 
ensure:

The protection of patient safety, particularly if scheduled visits to the site are 
postponed

The uninterrupted supply of drug to patients who continue to benefit from it, while 
assuring safety, even if they are encouraged to remain at home (guidance will be 
provided to the site)

The collection of safety and efficacy data, even if patients cannot keep their 
scheduled visits to the study site.
The following considerations may be applied in accordance with individual site policies and 
guidelines from regulatory authorities (FDA 2021, EMA 2021). he Sponsor will continue to 
follow regulatory guidelines for any updates related to the COVID-19 pandemic. If planned 
on-site monitoring visits are no longer possible, the Sponsor will consider optimizing the use of 
central and/or remote monitoring programs to maintain oversight of study sites. Alternative 
approaches will be implemented to maintain patient safety and study data quality and integrity, 
such as enhanced central monitoring, telephone contact with the sites to review study procedures, 
patient status and study progress, or remote monitoring of individual enrolled patients, where 
appropriate and feasible.

If a patient is unable to sign the informed consent in person, their consent may be 
obtained electronically or remotely via phone call or video call.

If a patient is unable to attend a scheduled on-site study visit and/or complete any 
protocol-required study assessments, the Sponsor should be contacted for further 
review. 

To ensure compliance with the protocol-required laboratory tests and assessments, the 
possibility for these tests to be performed at a local qualified laboratory or facility 
will be evaluated. The results of any tests or assessments performed by a local 
laboratory or facility must be communicated to the Investigator and documented in 
the patient’s source files and the eCRF. 

If it is not possible to have assessments performed at a local facility, the patient may 
be evaluated for safety via a phone call or video call, assuring the collection and 
follow-up of adverse events is documented in the patient’s source file. All C1 
assessments need to be performed. For C2 and beyond, a patient will not receive 
additional treatment without having laboratory and ECG assessments performed at 
least once during each cycle (eg, on C1D1).

Response assessments will need to be performed, as often as the circumstances allow, 
according to the protocol. If the patient is not able to visit the study site, alternatively, 
a local qualified imaging facility can be used. 

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
The results, including the images obtained from all radiographic procedures, should 
be sent to the Investigator. The imaging facility used, the timepoints, and the 
Investigator’s review of the images should be documented in the patient’s source files 
and the eCRF.

If a patient is diagnosed with COVID-19 or develops symptoms suggesting 
COVID-19, patients will be managed according to local guidelines. Symptomatic 
COVID-19 cases will be reported as AEs or SAEs; it is at the Investigator’s discretion 
to report asymptomatic COVID-19 cases. In the case of patients diagnosed with 
COVID-19 (symptomatic or asymptomatic), patients can only continue treatment 
with futibatinib if the Investigator considers that there is an individual positive 
risk/benefit balance, and once the patient has fully recovered from the COVID-19 
infection. The Sponsor should be made aware of the Investigator’s decision.

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7.
PHARMACOKINETICS
The PK population will consist of all patients who received at least one dose of futibatinib and 
have evaluable PK data for analysis. Blood samples will be obtained from all patients at the 
timepoints listed in Table 10 and used to determine plasma futibatinib concentrations. 
In the event that a patient interrupts treatment after the pre-dose sample is collected and restarts 
the treatment at a later date, a pre-dose sample should be collected. 
Table 10:
Pharmacokinetic Blood Sample Collection
Day of Study
(Time Window)
Collection Time Point (hours) in Relation to Futibatinib Administration 
(Time Window)
Pre-dose (from -30 min to just before dose)
1 hour ±30 min post-dose
Day 15 of Cycle 1
(± 3 days)
3 hours ±30 min post-dose

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8.
EFFICACY EVALUATIONS
8.1.
Cohorts A and B
8.1.1.
Efficacy Criteria
For patients in Cohorts A and B, response assessments (including CT/MRI) will be performed by 
the Investigator/local radiologist according to RECIST 1.1 guidelines (Eisenhauer et al. 2009). 
Planned time points for all efficacy assessments are provided in the Schedule of Events.
Results of the local 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 drug 
decisions. 
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. 
Note that patients who discontinue without documented disease progression should continue to 
undergo response 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.
8.1.2.
Method of Imaging
The same method of assessment and 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 response 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 visit) 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 
or 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.

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8.1.3.
Tumor Definitions
The following definitions are outlined according to RECIST 1.1 criteria:
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.
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 response 
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. 

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
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.” 
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).
8.1.4.
Response Criteria
Efficacy evaluation will include the assessment of target and non-target responses as well as 
objective responses. Responses will be assessed as defined in the SAP.
8.1.4.1.
Target and Non-Target Response Assessments
Assessments will be based on the definitions for target and non-target lesions described in 
Table 11. 

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Table 11:
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.
8.1.4.2.
Additional Criteria to Consider When Making 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]). 

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When effusions are known to be a potential adverse effect of treatment, cytological confirmation 
of the neoplastic origin of any effusion that appears or worsens during treatment when the 
measurable tumor has met criteria for response or SD is not mandatory, but might be performed 
to differentiate between response (or SD) and PD when substantial change of effusion and or 
ascites is noted. 
If a patient is discontinued from the study before PD occurs and receives local or regional 
palliative radiotherapy during the follow-up period, the irradiation site must be omitted from the 
response assessment of the patient; however, if the site is observed to demonstrate disease 
progression, this case should be judged as PD. 
For equivocal findings of progression (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.
8.1.5.
Objective Response Assessment
Assessments will be based on the definitions provided in Table 12 and Table 13. Since this is a 
non-randomized study, all responses (CR/PR) must be confirmed.
Table 12:
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

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Table 13:
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
8.2.
Cohort C
8.2.1.
Efficacy Criteria
Efficacy will be assessed by evaluation of:

Bone marrow histomorphology changes, standard cytogenetics, and FGFR molecular 
status

Peripheral blood assessment (blood count) including potentially FGFR molecular 
status

Positron emission tomography (PET) scan for fluorodeoxyglucose (FDG) avid lesions

Imaging (CT/MRI) in case of presence of solid lesions

Clinical assessment
If the Investigator determines that a patient has developed clinical disease progression 
manifested by symptomatic deterioration, the patient may stop treatment. Every effort should be 
made to document objective disease progression even after discontinuation of treatment.
8.2.2.
Response Criteria 
For patients in Cohort C, response will be determined based on disease presentation. 
Investigators will assess response based on the following response criteria:

Treatment Response Criteria for MDS/MPN (Savona et al. 2015)

Response Evaluation Criteria in Lymphoma (RECIL 2017) (Younes et al. 2017)

International Working Group (IWG) Response Criteria for AML (Cheson et al. 2003)
A review of the response assessments will be conducted by an adjudication committee. 
8.2.3.
Response Definitions
Response will be determined based on Investigators’ assessment of imaging, bone marrow, 
peripheral blood, and extramedullary disease. Assessments will be based on the definitions 
described in Table 14.

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Table 14:
Response Definitions for Cohort C
MLN Characteristic
MLN Only
Lymphoma Presentation
Leukemia Presentation
Response Criteria
Savona 2015a
RECIL 2017b
Cheson 2003c
Complete response (CR)
Must fulfill all criteria defined for 
CR 
Must fulfill all criteria defined 
for CR 

Must fulfill all criteria defined for 
morphologic complete response

CR does not include:
o
Morphologic leukemia-free state
o
Complete response with incomplete 
hematological recovery (CRi), or 
o
Cytologic complete response (CRc)
Partial response (PR)
Must fulfill all criteria defined for 
PR
Must fulfill all criteria defined 
for PR
Must fulfill all criteria defined for partial remission  
Complete response with 
incomplete blood count 
recovery (CRi)
N/A
N/A
Must fulfill all criteria defined for CRi
Complete cytogenetic 
response (CCyR)
Resolution of previously present 
chromosomal abnormality known 
to be associated with MLN (eg. 
8p11 translocation)
Must fulfill all criteria defined 
for CCyR (Savona 2015)a 
Must fulfill all criteria defined for cytogenetic 
complete response (CRc) (Cheson 2003)c and 
CCyR (Savona 2015)a
Partial cytogenetic 
response (PCyR)
≥50% reduction of chromosomal 
abnormality known to be 
associated with MLN (eg. 8p11 
translocation)
Must fulfill all criteria defined 
for PCyR (Savona 2015)a
Must fulfill all criteria defined for PCyR 
(Savona 2015)a
PD/Relapsed disease
Must fulfill all criteria defined for 
PD/relapsed disease 
Must fulfill all criteria defined 
for PD/relapsed disease 
Must fulfill all criteria defined for PD/relapsed 
disease 
a Savona, et al. An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults. 
Blood. 2015.
b Younes, et al. International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017). Ann Oncol. 2017.
c Cheson, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and 
Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003.

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8.3.
Efficacy Endpoints
The efficacy endpoints are provided in Table 4. Definitions of each endpoint are provided in 
Section 11.5.3.1.2 . For further information, refer to the SAP.

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9.
SAFETY EVALUATIONS
9.1.
Adverse Events
An AE is defined as 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. For this study, progression of the cancer under study is not considered an AE 
unless the Investigator deems it related to study drug.
All AEs will be collected from the time informed consent has been documented through 30 days 
after the last dose of any study drug (safety follow-up) or until the start of new antitumor 
therapy, whichever is earlier. 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.
Signs and symptoms of a preexisting disease should not be considered an AE, but should rather 
be considered baseline signs and symptoms. Clinically significant worsening of preexisting signs 
and symptoms is considered an AE.
9.2.
Reporting of Adverse Events
9.2.1.
Terms of Reported Adverse Events
All AEs will be documented in the eCRF according to the eCRF Completion Guidelines. 
Documentation should include onset and resolution/stabilization dates, severity/grade, 
relationship to study drug, and outcome of the event. 
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 one or more AEs.
9.2.2.
Severity of Adverse Events
The NCI-CTCAE V5.0 will be used to grade the severity of AEs.
9.2.3.
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.

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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 at least 
one of the following conditions is true:

The event occurred prior to study drug administration.

There is no reasonable possibility that the study drug caused the event. (“No 
reasonable possibility” means there is no evidence to suggest a causal relationship 
between the study drug and the AE)

The event does not follow a reasonable temporal sequence from administration of 
study drug and could have been produced by a documented preexisting condition, 
concomitant medication, or patient’s clinical state. 
9.2.4.
Outcome of Adverse Events
Record the outcome of AEs as follows:

Resolved

Not resolved

Fatal
9.2.5.
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 

Withdrawal of consent

Death

Other (eg, transfer to another hospital)

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9.3.
Laboratory Assessments
9.3.1.
Reporting and Evaluation of Laboratory Test Results
All laboratory results must be reviewed by the Investigator. A new laboratory 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 futibatinib. 
The NCI-CTCAE V5.0 will be used to grade the severity of laboratory data.
9.3.2.
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.
9.4.
Serious Adverse Events
9.4.1.
Definitions of Serious Adverse Events
An SAE is any untoward medical occurrence that at any dose: 

Results in death

Death due to disease progression or relapse is not considered an SAE unless the 
Investigator deems it related to the study drug.

Is life-threatening 

The term "life-threatening" 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. The 
following are not considered hospitalizations for the purposes of assessing 
seriousness (however, one of the other serious criteria may apply):

Emergency room visits <24 hours

Hospitalizations for pre-planned 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).

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
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). 
9.4.2.
Reporting of Serious Adverse Events (within 24 hours)
All SAEs occurring from the time informed consent has been documented through the Safety 
Follow-up Visit (30 days after the last dose of study drug or discontinuation, whichever is 
earlier) must be reported to Sponsor’s Pharmacovigilance group or its designee immediately and 
no later than 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 serious criterion. The SAE reporting process and contact 
information are provided in supplement guidelines.
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, or results of specific investigations) on a 
follow-up SAE form.
Investigators are not obligated to actively seek SAEs after the 30-day Follow-up. However, if the 
Investigator learns of any SAE (including a death) at any time after a participant has been 
discharged from the study, and the investigator considers the event to be reasonably related to the 
study treatment or participation, the investigator must promptly notify the Sponsor.
The Investigator also must submit further information if it is required by the Sponsor or the 
director of the study site or an institutional review board (IRB)/independent ethics committee 
(IEC).
Every SAE should be followed until it has resolved, stabilized, or returned to baseline.
9.4.3.
Reporting of Deaths (within 24 hours)
All deaths (except disease progression) occurring from the time informed consent has been 
documented through the Safety Follow-up Period (30 days after the last dose of study drug or 
discontinuation, whichever is earlier) must be reported immediately and no later than 24 hours 
from the time the Investigator first becomes aware of the death. The primary cause of the death 
should be reported as the SAE term, if available, and entered on the death page of the eCRF. 
Death due to disease progression is not a reportable event unless the Investigator deems it related 
to study drug. In the latter case, the event must be reported within 24 hours from the times the 
Investigator first becomes aware of the death.
9.5.
Other Safety Information
9.5.1.
Pregnancy
If a patient becomes pregnant while in the study, the study drug must be immediately 
discontinued. Pregnancy information in a female patient (or for the female partner of a male 

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patient) should be reported to Sponsor’s Pharmacovigilance or designee via the Pregnancy Form 
as soon as possible from the time the Investigator first becomes aware of a pregnancy or its 
outcome.
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 or designee. Pregnancies must be followed to outcome by the Investigator, 
even after study completion. 
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 an SAE to the Sponsor’s Pharmacovigilance or 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.
9.5.2.
Overdose 
An overdose is the accidental or intentional use of a drug in an amount higher than the dose 
being studied. An overdose or incorrect administration of study drug is not itself an AE, but it 
may result in an AE. 
An overdose that results in an AE should be reported to Sponsor’s Pharmacovigilance or 
designee within 24 hours from the time the Investigator first becomes aware of its occurrence.

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10.
BIOMARKER EVALUATION
10.1.
Biomarker Assessments
10.1.1.
Objectives and Background
Exploratory objectives of this study are to assess the possible impact of specific genetic 
alterations or other laboratory abnormalities on the efficacy of futibatinib.  
Biomarkers will be tested using analytically validated assay at a central laboratory.
All biomarker assessments described in this section will be performed at the timepoints shown in 
the Schedule of Events; methods of sample collection and preparation will be described in a 
separate Laboratory Manual.
10.1.2.
Assessment of FGF/FGFR Aberrations in Blood
A blood sample will be collected to assess FGF/FGFR aberrations in ctDNA as described in the 
Schedule of Events and where local regulations allow. In addition to assessing ctDNA as a 
pharmacodynamic biomarker, samples or a set of samples, will be used to investigate its possible 
utility as a complimentary or an alternative to tumor tissues for the future potential companion 
diagnostic development. Samples will be collected and stored, as per the Laboratory Manual, and 
analyzed in batches.
10.1.3.
Tissue Samples
Archival or fresh tumor/bone marrow biopsy samples will be collected during screening to 
retrospectively confirm FGFR gene status at the Sponsor’s designated central laboratories or for 
the purpose of a bridging study should companion diagnostics be warranted (fine needle 
aspiration is not acceptable). Formalin-fixed, paraffin embedded (FFPE) tissue blocks are 
preferred to slides. The remaining samples may be stored at the Sponsor’s designated central 
laboratories for up to 10 years after study completion for future testing or companion diagnostic 
development if warranted.
10.2.
Sample Storage and Disposal
Samples or leftover samples will be stored for a maximum of 10 years following the completion 
of the study at central laboratories. These samples could be used to develop companion 
diagnostics and to investigate the genes or other biomarkers related to efficacy or resistance of 
futibatinib in the future. After the storage period ends, samples will be destroyed.
10.3.
Analytical Procedures
Patients will be enrolled depending on local results but tissue samples will be collected and 
stored at central location for possible confirmatory testing, molecular profiling, and/or 
companion diagnostic development if warranted by the clinical response.
Analyzing plasma ctDNA will be conducted retrospectively in batches on an adequately 
validated assays at central lab(s). 
The detailed analytical procedures will be described in the SAP for Biomarkers.

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11.
STATISTICAL CONSIDERATIONS
The statistical analysis methods will be documented in detail in the SAP.
11.1.
Estimation of Sample Size
A total of approximately 155 patients will be enrolled in the study. 
Cohort A
Approximately 100 patients with solid tumors harboring FGFR rearrangements will be enrolled 
in Cohort A. Sample size considerations are based on differentiating a null ORR of 10% with a 
target ORR of 25%. Assuming the true ORR is 25%, the study has over 90% power to reject the 
null hypothesis that the true ORR is ≤10%, considering a 2-sided alpha of 5%.
A 2-stage Simon design (Simon 1989) will be used for futility assessment, comparing a poor 
response of ≤10% vs a promising response of ≥25%, at a 5% 1-sided significance level and 
approximate 90% power. In Stage 1 (futility assessment), enrollment will include 35 patients and 
accrual will continue to Stage 2, if at least 4 (11.4%) of 35 patients respond (CR or PR).
If the Stage 1 futility boundary is exceeded, Stage 2 will be open and require at least 
25 additional patients. To further provide a more precise estimate of objective response rate and 
a better evaluation of safety profile, a total of 100 patients will be enrolled.
The entire population in Cohort A (total of 100 patients) will be analyzed as specified in the 
objectives. Table 15 summarizes the 95% exact CI for the target ORRs ranging from 17% to 
30% with a sample size of 100. At observed ORR = 17%, the lower bound of the 95% CI 
excludes 10%, which is the null hypothesis ORR rate. This translates to observing at least 
17 responders out of 100 treated patients (ORR of 17.0% with 95% CI 10.2%-25.8%).   
Table 15:
Observed ORR with Exact 95% Confidence Interval (Cohort A)
ORR
95% Exact Confidence Interval
17%
[10.2% – 25.8%]
20%
[12.7%-29.2%]
25%
[16.9%-34.7%]
30%
[21.2%-40.0%]
Cohort B
Approximately 35 patients with gastric or GEJ cancer harboring FGFR2 amplification will be 
enrolled in Cohort B. Sample size considerations are based on differentiating a historical control 
ORR of 10% or less, with a target ORR of 35%. Assuming the true ORR is 35%, the cohort has 
approximately 96% power to reject the null hypothesis that the true ORR is ≤10%, considering a 
2-sided alpha of 5%. With a sample size of 35, observing at least 8 responders will have a 95% 
CI lower bound excluding 10% ORR of 23% with 95% CI (10.4%-40.1%)(Table 16). 

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Table 16:
Observed ORR with Exact 95% Confidence Interval (Cohort B)
ORR
95% Exact Confidence Interval
23%
[10.4%-40.1%]
29%
[14.6%-46.3%]
37%
[21.5%-55.1%]
Cohort C
Approximately 20 patients with myeloid or lymphoid neoplasms harboring FGFR1 
rearrangements will be enrolled in Cohort C. Sample size considerations are based on 
differentiating a historical control CR rate of 10% or less with a target CR rate of 50%. 
Assuming the true CR rate is 50%, the cohort has over 95% power to reject the null hypothesis 
that the true CR rate is ≤10%, considering a 2-sided alpha of 5%.
Observing at least 6 responders out of 20 treated patients will have a 95% CI lower bound 
excluding 10% CR rate of 30% with 95% CI (11.9%-54.3%) (Table 17). 
Table 17:
Observed CR Rate with Exact 95% Confidence Interval (Cohort C)
CR Rate
95% Exact Confidence Interval
30%
[11.9%-54.3%]
40%
[19.1%-64.0%]
50%
[27.2%-72.8%]
11.2.
Timing of Analysis
The Sponsor will review the data at the time Cohort A has the required number of patients 
(n=35) to determine if that particular cohort should continue. Additional interim analyses may be 
performed if required for regulatory purposes. Should Cohort A continue enrollment, the primary 
analysis for Cohort A will be carried out when all patients have been followed up for at least 
6 months or have discontinued the study. For Cohort B and Cohort C, the primary analysis will 
be at the time when all patients have been followed up for at least 6 months or have discontinued 
the study in each cohort. 
11.3.
Analysis Populations
The analysis populations in the study are defined in Table 18. 

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Table 18:
Definitions of Analysis Populations
Analysis Population
Definition
All Enrolled Population
All patients who provided documented informed 
consent in this study
All Treated Population/Full Analysis Set
All enrolled patients who received at least 1 dose of 
study drug
Pharmacodynamic/Biomarker Evaluable Set
All patients in the All Treated Population who have 
evaluable pharmacodynamic/biomarker data for 
analyses
11.4.
Criteria for Handling of Patient Data
The criteria for handling of patient data are provided in the SAP.
11.5.
Statistical Analyses
This section outlines the statistical methodology to be used to summarize the study results. A 
more detailed methodology for summary and statistical analyses of the data collected in this 
study are documented in the SAP. The SAP will be prepared as a separate document by the 
Sponsor.
11.5.1.
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.
11.5.2.
Study Drug Administration 
In the All Treated Population, the following analyses will be performed by dose level:

Administration status

The total dose, total duration of administration, and the number of administration 
cycles will be summarized by all treated patients/each intervention group.

Status of administration completion

The rate of administration completion will be presented by cycle.

The presence or absence of study discontinuation and reasons for study 
discontinuation will be tabulated by cycle.

Dose intensity

Actual dose intensity and relative dose intensity in each patient will be calculated, and 
descriptive statistics will be presented.

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11.5.3.
Efficacy Analyses 
All efficacy analysis will be performed using the All Treated Population
A description of each efficacy endpoint is provided in Table 4 and Table 5. See the SAP for 
more detailed information on the efficacy analyses.
11.5.3.1.
Cohorts A and B
11.5.3.1.1. Primary Efficacy Analysis
Objective response rate is defined as the proportion of patients with objective evidence of CR or 
PR (per RECIST 1.1). The evaluation of ORR will be based on an independent central review of 
radiologic images. At the analysis stage, the best objective response will be assigned for each 
patient as the best response recorded after initiation of study drug 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.
11.5.3.1.2. Secondary Efficacy Analyses
Duration of response is a key efficacy endpoint: 

Duration of response will only be evaluated in patients with an 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 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 response assessments prior to initiation of the 
subsequent anticancer therapy.
Additional efficacy endpoints include:

Overall response rate and DCR based on Investigator assessment will be determined (per 
RECIST 1.1) as described for the primary analysis of ORR based on independent central 
review of radiologic images (Section 11.5.3.1.1).   

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 
response 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 anticancer 
therapy without a prior reported progression will be censored at the last response assessment 
prior to initiation of the subsequent anticancer therapy. 

Overall survival will be analyzed in a similar manner to PFS. In the absence of confirmation 
of death or for patients who are alive as of the OS cut-off date, survival time will be censored 
at the last known date that the patient was alive.

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11.5.3.2.
Cohort C
11.5.3.2.1. Primary Analysis
Complete response rate defined as the proportion of patients who achieved a CR will be 
calculated and the exact 2-sided CI will also be derived using the Clopper Pearson methodology.
11.5.3.2.2. Secondary Analyses
The overall response, CR+CRi (leukemia presentation only), CCyR, and PCyR rates will be 
calculated and the exact 2-sided CIs will also be derived using the Clopper-Pearson 
methodology.
Duration of CR (only in patients who achieved a CR), duration of CR+CRi (only in patients who 
achieved a CR/CRi [leukemia presentation only]), and duration of response (only in patients with 
an objective response of CR, CRi [leukemia presentation only], or PR) will be estimated using 
the Kaplan-Meier method. Patients who are alive and progression-free as of the analysis cut-off 
date will be censored at their last evaluable 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 response 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 response 
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 anticancer therapy without a prior 
reported progression will be censored at the last response assessment prior to initiation of the 
subsequent anticancer therapy.
Relapse-free survival will only be evaluated in patients with an objective response of CR and 
measured from the first date of achieving CR until the first date of relapsed disease or death from 
any cause, whichever occurs first. Patients who die without a reported disease relapse will be 
considered to have relapsed on the date of their death. Patients who did not relapse or die will be 
censored on the date of their last response assessment. Patients who started any subsequent 
anticancer therapy without a prior reported relapse will be censored at the last response 
assessment prior to initiation of the subsequent anticancer therapy.
Event-free survival will be estimated only for patients with leukemia presentation using the 
Kaplan-Meier method. EFS is defined as the time from first dose of study drug to treatment 
failure, relapse after CR (if applicable), or death from any cause, whichever occurs first. For a 
patient with none of these events before the end of study follow-up, observation of EFS is 
censored at the date of last contact prior to the analysis cut-off date. If the patient does not 
achieve a CR, EFS is defined as the point of treatment failure or death, whichever comes first. 
Treatment failure for EFS is defined as PD in this study.
Overall survival will be analyzed in a similar manner to PFS. In the absence of confirmation of 
death or for patients who are alive as of the OS cut-off date, survival time will be censored at the 
last known date that the patient was alive.

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11.5.4.
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 V5.0, 
where applicable. 
Concomitant medications will be coded according to the WHO 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 futibatinib. In addition, separate 
summaries of SAEs and Grade 3 or 4 AEs will be presented.
For all AEs that occurred between the patient providing documented informed consent 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 V5.0 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 electrocardiogram findings will be presented by patient.
11.5.5.
Pharmacokinetic Analysis
The PK data obtained in this study will be combined with data from other studies in the clinical 
development program to develop a popPK model. This model will be used to evaluate the effects 
of intrinsic and extrinsic covariates on the PK of futibatinib and to estimate measures of 
individual exposure (such as steady-state peak, trough and area under the plasma drug 
concentration-time curve). Model estimated exposures will be used for exposure-response 
analyses of selected efficacy and safety endpoints. The results of popPK and exposure-response 
analyses will be reported separately.
11.5.6.
Pharmacodynamic/Biomarker Analysis
The exploratory pharmacodynamic/biomarker endpoints are described in Section 10.
Pharmacodynamic and biomarker data will be summarized descriptively using all patients in the 
Pharmacodynamic/Biomarker Evaluable Set who have evaluable data available.

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12.
ADMINISTRATIVE CONSIDERATIONS
12.1.
Protocol Compliance
The Investigator must agree to comply with all aspects of the protocol. 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. The new Investigator must accept the 
responsibility in writing and be approved by the Sponsor and the IRB/IEC.
12.2.
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.
12.3.
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.
12.4.
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.
12.5.
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, all relevant personnel will receive electronic data capture access according to their 
roles in the study.
An eCRF should be completed for each screened and enrolled patient.
The Investigator, or assigned personnel, should verify the data and correct as necessary prior to 
approval of the eCRFs.

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12.6.
Access to Source Data/Documents
The Investigator and the site must make all study-related records available for study-related 
monitoring, audit, IRB/IEC review, and regulatory inspection.
12.6.1.
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.
12.6.2.
Access to Source Data
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 
Investigator.
12.7.
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 these data by any unauthorized third party.
12.8.
Responsibilities of Recordkeeping
12.8.1.
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 of 
Technical Requirements for Pharmaceuticals for Human Use (ICH) E6 Guidelines. In 
multinational studies, non-United States sites will be considered non-Investigational New Drug 
(IND) sites. Non-IND sites will be required to follow local regulations and ICH Guidelines.
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.

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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.
12.8.2.
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.
12.9.
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 and the site 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.
12.10.
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.
12.11.
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.
12.12.
Study Administrative Structure 
The study organization details will be maintained in a supplement.

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13.
QUALITY CONTROL AND QUALITY ASSURANCE
The Sponsor will perform quality control and quality assurance procedures in accordance with 
the Sponsor's standard operating procedures (SOPs) to ensure the quality of the clinical study.
13.1.
Quality Control
The Sponsor is responsible for controlling the quality of the clinical study according to the SOPs 
regarding study operation, monitoring, data collection and management, statistical analysis, and 
handling of safety information to verify that the study-related activities have been fulfilled.
13.2.
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 and the site 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 and the site 
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 
and the site 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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14.
ETHICS
14.1.
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.
14.2.
Documented Informed Consent
The ICF(s) must be approved by the IRB/IEC before a patient’s consent to any study-related 
activity. It must be in a language that the patient can read and understand. The ICF process 
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 documented 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) during their participation in the study (including during 
survival follow-up).
14.3.
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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15.
PUBLICATION POLICY
15.1.
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.
The Investigator(s) 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.
15.2.
Secondary Use of Data
The Sponsor maintains the right to secondary use of data in this study.
Secondary use of data describes the use of data from this study for other study/studies for 
purposes including, but not limited to, drug development and/or academic research. Secondary 
use of data also includes external offerings of study data to domestic and/or foreign 
organization(s), other companies and researcher(s), on a case by case basis.

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16.
REFERENCES
Bain BJ, Gilliland DG, Horny HP, Vardiman JW, et al. Myeloid and lymphoid neoplasms with 
eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1. Haematologica. 
2010;95:696-698.
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.
Buas MF, Vaughan TL. Epidemiology and risk factors for gastroesophageal junction tumors: 
understanding the rising incidence of this disease. Semin Radiat Oncol. 2013;23:3-9. 
Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, et al. Revised 
recommendations of the International Working Group for Diagnosis, Standardization of 
Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in 
Acute Myeloid Leukemia. J Clin Oncol. 2003;21:4642-4649.
Courjal F, Cuny M, Simony-Lafontaine J, Louason G, Speiser P, Zeillinger R, et al. Mapping of 
DNA amplifications at 15 chromosomal localizations in 1875 breast tumors: definition of 
phenotypic groups. Cancer Res. 1997;57:4360-4367. 
Deng N, Goh LK, Wang H, Das K, Tao J, Tan IB, et al. A comprehensive survey of genomic 
alterations in gastric cancer reveals systematic patterns of molecular exclusivity and 
cooccurrence among distinct therapeutic targets. Gut. 2012;61:673-684.
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.
[EMA] European Medicines Agency. Guidance on the Management of Clinical Trials during the 
COVID 19 (Coronavirus) Pandemic. Version 4. 04 February 2021.
[FDA] US Food and Drug Administration. FDA Guidance on Conduct of Clinical Trials of 
Medical Products during COVID-19 Public Health Emergency. Updated 27 January 2021.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of 
cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893-2917. 
Gallo LH, Nelson KN, Meyer AN, Donoghue DJ. Functions of fibroblast growth factor receptors 
in cancer defined by novel translocations and mutations. Cytokine Growth Factor Rev. 
2015;26:425-449. 
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.
Jackson CC, Medeiros LJ, Miranda RN. 8p11 myeloproliferative syndrome: a review. Hum 
Pathol. 2010;41:461-476.

Futibatinib (TAS-120)
Protocol -TAS-120-202 (Amendment 2)
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Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality 
rates and trends. Cancer Epidemiol Biomarkers Prev. 2010;19:1893-1907. 
Jung EJ, Jung EJ, Min SY, Kim MA, Kim WH. Fibroblast growth factor receptor 2 gene 
amplification status and its clinicopathologic significance in gastric carcinoma. Hum Pathol. 
2012;43:1559-1566. 
Kunii K, Davis L, Gorenstein J, Hatch H, Yashiro M, Di Bacco A, et al. FGFR2- amplified 
gastric cancer cell lines require FGFR2 and Erbb3 signaling for growth and survival. Cancer Res. 
2008;68:2340-2348.
Lacombe D, Burock S, Bogaerts J, Schoeffski P, Golfinopoulos V, Stupp R. The dream and 
reality of histology agnostic cancer clinical trials. Mol Oncol. 2014; 8:1057-1063. 
Liu YJ, Shen D, Yin X, Gavine P, Zhang T, Su X, et al. HER2, MET and FGFR2 oncogenic 
driver alterations define distinct molecular segments for targeted therapies in gastric carcinoma. 
Br J Cancer. 2014;110:1169-1178. 
Loriot Y, Necchi A, Hoon Park S, Garcia-Donas J, Huddart R, Burgess E, et al. Erdafitinib in 
locally advanced or metastatic urothelial carcinoma. N Engl J Med. 2019;381:338-348.
Macdonald D, Aguiar RC, Mason PJ, Goldman JM, Cross NC. A new myeloproliferative 
disorder associated with chromosomal translocations involving 8p11: a review. Leukemia. 
1995;9:1628-1630. 
Macdonald D, Reiter A, Cross NC. The 8p11 myeloproliferative syndrome: a distinct clinical 
entity caused by constitutive activation of FGFR1. Acta Haematol. 2002;107:101-107.
Meric-Bernstam F, Bahleda R, Hierro C, Sanson M, Bridgewater J, Arkenau HT, et al. 
Futibatinib, an irreversible FGFR1-4 inhibitor, in patients with advanced solid tumors harboring 
FGF/FGFR abberations: a phase I dose-expansion study. Cancer Discov. 
2021;candisc.0697.2021.
Oken MM, Creech, RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity 
and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 
1982;5:649-655.
Savona MR, Malcovati L, Komroki R, Tiu RV, Mughal TI, Orazi A, et al. An international 
consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative 
neoplasms (MDS/MPN) in adults. Blood. 2015;125:1857-1865.
Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 
1989;10:1-10.
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;33:3199-3212.
Turner N, Grose R. Fibroblast growth factor signaling: from development to cancer. Nature Rev 
Cancer. 2010;10:116-129.

Futibatinib (TAS-120)
Protocol -TAS-120-202 (Amendment 2)
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Villafuerte-Gutiérrez P, López Rubio M, Herrera P, Arranz E. A case of myeloproliferative 
neoplasm with BCR-FGFR1 rearrangement: favorable outcome after haploidentical allogeneic 
transplantation. Case Rep Hematol. 2018, Article ID 5724960, 4 pages. 
Williams SV, Hurst CD, Knowles MA. Oncogenic FGFR3 gene fusions in bladder cancer. Hum 
Mol Genet. 2013;22:795-803.
Wu YM, Su F, Kalyana-Sundaram S, Khazanov N, Ateeq B, Cao X, et al. Identification of 
targetable FGFR gene fusions in diverse cancers. Cancer Discov. 2013;3:636-647.
Yoshihara K, Wang Q, Torres-Garcia W, Zheng S, Vegesna R, Kim H, Verhaak RGW. The 
landscape and therapeutic relevance of cancer-associated transcript fusions. Oncogene. 
2015;34:4845-4854. 
Younes A, Hilden P, Coiffier B, Hagenbeek A, Salles G, Wilson W, et al. International Working 
Group consensus response evaluation criteria in lymphoma (RECIL 2017). Ann Oncol. 
2017;28:1436-1447.

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APPENDIX A. ECOG PERFORMANCE
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. CLASSIFICATION OF SUBSTRATES, INHIBITORS, AND 
INDUCERS OF CYP ENZYMES AND TRANSPORTERS
The classification below is based on the FDA Drug Development and Drug Interactions | Table of Substrates, 
Inhibitors and Inducers. Content current as of 03/10/2020. https://www.fda.gov
Example of CYP3A Inhibitors
Cytochrome P450 
(CYP) Enzymes
Strong Inhibitorsa
≥ 5-fold increase in AUC
Moderate inhibitorsb
≥ 2 but < 5-fold increase in AUC
CYP3A
boceprevir, clarithromycin, cobicistat, conivaptan, 
danoprevir and ritonavir, diltiazem, elvitegravir and 
ritonavir, grapefruit juice,c indinavir and ritonavir, 
idelalisib, itraconazole, ketoconazole, lopinavir and 
ritonavir, 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
a
Strong inhibitors are drugs that increase the area under the concentration-time curve (AUC) of sensitive index substrates of a 
given metabolic pathway ≥5-fold.
b
Moderate inhibitors are drugs that increase the AUC of sensitive index substrates of a given metabolic pathway ≥2 to 
<5-fold.
c
The effect of grapefruit juice varies widely among brands and is concentration-, dose-, and preparation dependent. 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).
Example of CYP3A Inducers
Cytochrome P450 
(CYP) Enzymes
Strong Inducers
≥ 80% decrease in AUC
Moderate Inducers
50%-80% decrease in AUC
CYP3A
carbamazepine, enzalutamide, mitotane, 
phenytoin, rifampin, St. John’s worta
bosentan, efavirenz, etravirine, modafinil
a
The effect of St. John’s wort varies widely and is preparation-dependent.
Example of CYP3A Substrates
Cytochrome P450 
(CYP) Enzymes
Sensitive substratesa
Moderate sensitive substrateb
CYP3Ac
alfentanil, avanafil, budesonide, buspirone, 
conivaptan, darifenacin, darunavir, dasatinib, 
dronedarone, ebastine, eletriptan, eplerenone, 
everolimus, felodipine, ibrutinib, indinavir, 
lomitapide, lovastatin, lurasidone, maraviroc, 
midazolam, naloxegol, nisoldipine, quetiapine, 
saquinavir, sildenafil, simvastatin, sirolimus, 
tacrolimus, ticagrelor, tipranavir, tolvaptan, 
triazolam, vardenafil
alprazolam, aprepitant, atorvastatin, 
colchicine, eliglustat, pimozide, 
rilpivirine, rivaroxaban, tadalafil
a
Sensitive substrates are drugs that demonstrate an increase in AUC of ≥5-fold with strong index inhibitors of a given 
metabolic pathway in clinical drug-drug interaction studies.
b
Moderate sensitive substrates are drugs that demonstrate an increase in AUC of ≥2 to <5-fold with strong index inhibitors of 
a given metabolic pathway in clinical drug-drug interaction studies.
c
Because a number of CYP3A substrates (eg, darunavir, maraviroc) are also substrates of MDR1 (P-gp), the observed 
increase in exposure could be due to inhibition of both CYP3A and MDR1 (P-gp).

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Example of Inhibitors for P-gp and BCRP
Transporters
Gene
Inhibitor
P-gpa
ABCB1
Amiodarone, carvedilol, clarithromycin, dronedarone, 
itraconazole, lapatinib, lopinavir and ritonavir, propafenone, 
quinidine, ranolazine, ritonavir, saquinavir and ritonavir, 
telaprevir, tipranavir and ritonavir, verapamil
BCRPb
ABCG2
Curcumin, cyclosporine A, eltrombopag
a
P-gp: (1) AUC fold-increase of digoxin ≥2 with co-administration and (2) in vitro inhibitor.
b
BCRP: (1) AUC fold-increase of sulfasalazine ≥1.5 with co-administration and (2) in vitro inhibitor. Cyclosporine A and 
eltrombopag were also included, although the available DDI information was with rosuvastatin, where inhibition of both 
BCRP and OATPs may have contributed to the observed interaction.
Example of Substrates for P-gp and BCRP
Transporters
Gene
Substrate
P-gpa
ABCB1
Dabigatran, digoxin, fexofenadine
BCRPb
ABCG2
Rosuvastatin, sulfasalazine
a
P-gp: (1) AUC fold-increase ≥2 with verapamil or quinidine co-administration and (2) in vitro transport by P-gp expression 
systems, but not extensively metabolized.
b
BCRP: (1) AUC fold-increase ≥2 with pharmacogenetic alteration of ABCG2 (421C>A) and (2) in vitro transport by BCRP 
expression systems.

Taiho
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Clinical Approval
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Clinical Study Protocol
A PHASE 2 STUDY OF FUTIBATINIB IN PATIENTS
WITH SPECIFIC FGFR ABERRATIONS 
Futibatinib (TAS-120)
Protocol TAS-120-202
Issue Date: 08 November 2019 (Not implemented)
Amendment 1:  07 February 2020
IND Number: 145393
EudraCT Number: 2019-004084-49
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 (ICH), Good Clinical Practice (GCP) 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.

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PROTOCOL SYNOPSIS
Protocol Title: 
A Phase 2 Study of Futibatinib in Patients with Specific FGFR Aberrations
Rationale:
Fibroblast growth factor receptor (FGFR) signaling plays a crucial role in cancer cell proliferation, 
migration, angiogenesis, and survival. Recent studies have uncovered increasing evidence that 
deregulated FGFRs can function as driving oncogenes in certain tumor types, maintaining the malignant 
properties of cancer cells. When FGFRs are amplified, rearranged, or undergo fusion, aberrant activation 
of downstream pathways results in mitogenic, mesenchymal, and antiapoptotic responses in cells. 
Therefore, FGFRs are attractive targets for therapeutic intervention in cancer treatment.
The Phase 2 study described in this protocol will evaluate the efficacy and safety of futibatinib in patients 
with FGFR aberrations in 3 distinct cohorts. Patients will be enrolled into 1 of 3 cohorts: patients with 
advanced, metastatic, or locally-advanced solid tumors harboring FGFR rearrangements (excluding 
primary brain tumors and intrahepatic cholangiocarcinoma [iCCA]); patients with gastric or gastro-
esophageal junction (GEJ) cancer harboring FGFR2 amplification; and patients with myeloid or lymphoid 
neoplasms harboring FGFR1 rearrangements.

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Study Objectives and Endpoints:
Cohorts A and B
Primary
To evaluate the objective response rate (ORR) in 
patients with solid tumors harboring FGFR
rearrangements or gastric cancer (including GEJ 
cancer) harboring FGFR2 amplifications based on 
independent central review of radiologic images (IRC)
ORR, defined as the proportion of patients experiencing a 
best overall response of partial response (PR) or complete 
response (CR) (per Response Evaluation Criteria in Solid 
Tumors, Version 1.1 [RECIST 1.1]), based on IRC 
Secondary 

To evaluate ORR based on investigator 
assessment 

To evaluate progression-free survival (PFS), 
disease control rate (DCR), duration of response 
(DOR), and overall survival (OS)

To assess safety and tolerability

ORR, defined as the proportion of patients 
experiencing a best overall response of partial 
response of PR or CR (per RECIST 1.1), based on 
investigator assessment

DCR, defined as the proportion of patients 
experiencing a best overall response of stable disease 
(SD), PR, or CR (per RECIST 1.1), based on IRC 

DOR defined as the time from the first documentation 
of response (CR or PR per RECIST 1.1 based on 
IRC) to the first documentation of objective tumor 
progression or death due to any cause, whichever 
occurs first

PFS, defined as the time from first dose of study 
therapy to the date of death (any cause) or disease 
progression (based on IRC), whichever occurs first

OS, defined as the time from the date of first dose to 
the death date

Safety based on reported AEs and on-study laboratory 
parameters, graded according to the National Cancer 
Institute—Common Terminology Criteria for 
Adverse Events , Version 5.0 (NCI-CTCAE V5.0).
Exploratory

To assess the possible impact of genetic 
alterations or other laboratory abnormalities on the 
efficacy of futibatinib 

To assess the population pharmacokinetics 
(3opPK) and exposure response

Assessment of pharmacodynamic effects will be 
analyzed from circulating tumor DNA (ctDNA), 
tumor biopsy, and/or plasma samples.

PopPK and exposure response will be analyzed from 
blood samples collected during treatment.

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Cohort C
Overall Objective
The overall objective of Cohort C is to assess the clinical activity of futibatinib as monotherapy in the treatment of 
patients with myeloid/ lymphoid neoplasms (MLN) harboring FGFR1 rearrangements.
Primary
To evaluate complete response rate 
CR rate, defined as the proportion of patients who 
achieved a CR
Secondary 

To evaluate:
o
ORR
o
CR + complete response with incomplete 
hematological recovery (CRi) rate
o
Complete or partial cytogenetic responses 
(CCcyR or PCyR) rate
o
Duration of CR
o
Duration of CR+CRi
o
DOR
o
Time-to-events 

To assess the safety and tolerability

ORR, defined as the proportion of patients who 
achieved a CR, CRi, or PR

CR+CRi rate, defined as the proportion of patients 
who achieved a CR or CRi 

CCyR rate, defined as the proportion of patients who 
achieved CCyR

PCyR rate, defined as the proportion of patients who
achieved PCyR

Duration of CR defined as the time from the first 
documentation of CR to the first documentation of 
objective tumor progression or death due to any 
cause, whichever occurs first

Duration of CR+CRi defined as the time from the 
first documentation of CR/CRi to the first 
documentation of objective tumor progression or 
death due to any cause, whichever occurs first

DOR defined as the time from the first 
documentation of CR, CRi, or PR to the first 
documentation of objective tumor progression or 
death due to any cause, whichever occurs first

PFS, defined as the time from first dose of study 
therapy to the date of death (any cause) or disease 
progression, whichever occurs first

Relapse-free survival (RFS), defined as the time from 
the first documentation of CR to the first 
documentation of disease relapse or death due to any 
cause, whichever occurs first. 

Event-free survival (EFS) (leukemia presentation 
only), defined as the time from first dose of study 
therapy to treatment failure, disease relapse after CR, 
or patient death from any cause. 

OS, defined as the time from the date of first dose to 
the death date. 

Safety based on reported AEs and on-study 
laboratory parameters, graded according to the 
NCI-CTCAE V5.0
Exploratory

To assess the pharmacodynamic effects of 
treatment with futibatinib

To assess the association of response and 
mechanisms of resistance in tumor tissue biopsies 
and/or blood

To assess the popPK and exposure response

Changes in pharmacodynamic markers assessed in 
bone marrow tissue biopsies.

Exploratory association of tissue and/or blood 
markers with tumor efficacy endpoints and/or tumor 
resistance to futibatinib.

PopPK and exposure response will be analyzed from 
blood samples collected during treatment

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Overall Design:
Study TAS-120-202 is an open-label, multinational, 3-arm Phase 2 study evaluating the efficacy, safety, 
tolerability, pharmacokinetics (PK), and pharmacodynamics of futibatinib in patients with FGFR
aberrations. Eligible patients will be assigned to 1 of 3 treatment cohorts based on diagnosis and FGFR
gene aberration status.
Patients will receive futibatinib at an oral dose of 20 mg once a day on a continuous 28-day cycle. 
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 (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, the patient withdraws consent, or the study is terminated early by 
the Sponsor.
Additional cohorts may be added in the future in case of new emerging efficacy data. This change will be 
implemented through a protocol amendment which will describe the rationale for the addition(s).
Number of Patients: 
The study will enroll approximately 60 patients with advanced, metastatic, or locally-advanced solid 
tumor harboring FGFR rearrangements, except for primary brain tumor or iCCA); 35 patients with 
advanced, metastatic, or locally-advanced gastric or GEJ cancer harboring FGFR2 amplification; and 
20 patients with MLN harboring FGFR1 rearrangements.
Entry Criteria: 
Inclusion Criteria
1.
Provide written informed consent
2.
≥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.
Has recovered from the acute toxic effects of prior anticancer therapy to baseline or Grade 1 (except 
toxicities which are not clinically significant such as alopecia)
5.
Known FGFR aberration status and tumor type that meet all of the criteria for 1 of the following 
cohorts: 
a.
Cohort A
i.
Histologically-confirmed, locally-advanced, advanced, or metastatic solid tumors 
harboring a FGFR1-4 rearrangement determined in tumor tissue using next-generation 
sequencing (NGS), fluorescence in situ hybridization (FISH), or other assays that can 
determine gene rearrangements in tumor tissues. Patients with primary brain tumor or 
iCCA are not eligible.
ii.
Measurable disease per RECIST 1.1 

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iii.
Had disease progression/recurrence after standard treatment for their advanced or 
metastatic cancer 
b.
Cohort B
i.
Histologically-confirmed, locally-advanced, advanced, or metastatic gastric or GEJ cancer 
harboring a FGFR2 amplification. The tumor must have an FGFR2/CEN10 ratio of ≥5 or 
an FGFR2 copy number ≥10 signals per cell determined in tumor tissue using NGS, FISH, 
or other assays that can determine gene amplification in tumor tissues. 
ii.
Measurable disease per RECIST 1.1
iii.
Received at least 2 prior systemic regimens for advanced/metastatic disease
iv.
Experienced disease progression/recurrence during or after the most recent prior systemic 
treatment for advanced/metastatic gastric or GEJ cancer
c.
Cohort C
i.
Confirmed MLN with a FGFR1 rearrangement as defined by WHO criteria 
ii.
Not a candidate for hematological stem cell transplant (HSCT) or relapsed after HSCT 
and donor lymphocyte infusion, and progressed and not a candidate for other therapies
6.
Has archival or fresh tumor tissue (preferably in block format) available to send to central laboratory.
7.
Adequate organ function as defined by the following criteria:
a.
Cohorts A and B:
i.
Absolute neutrophil count (ANC) ≥ 1.0 × 109/L
ii.
Platelet count ≥ 75,000/mm3 (≥75 × 109/L) 
iii.
Hemoglobin ≥ 9.0 g/dL
iv.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 × upper limit 
of normal (ULN); if liver function abnormalities are due to underlying liver metastasis, 
AST and ALT ≤ 5.0 × ULN.
v.
Total bilirubin ≤ 1.5 × ULN, or ≤ 3.0 × ULN for patients with Gilbert’s syndrome.
vi.
Creatinine clearance (CrCl) (calculated or measured value): ≥40 mL/min. For calculated 
CrCl, use the Cockcroft-Gault formula (Section 6).
vii. Phosphorus <1.5 ULN
b.
Cohort C
i.
ALT and AST ≤3.0 × ULN; if liver function abnormalities are due to underlying liver 
metastasis, AST and ALT ≤ 5.0 × ULN.
ii.
Total bilirubin ≤ 1.5 × ULN, or ≤ 3.0 × ULN for patients with Gilbert’s syndrome.
iii.
CrCl (calculated or measured value): ≥40 mL/min.  For calculated CrCl, use the 
Cockcroft-Gault formula (Section 6).
iv.
Phosphorus <1.5 ULN
8.
Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test prior to 
administration of the first dose of futibatinib. Female patients are not considered to be of child-
bearing potential if they are post-menopausal, defined as no menses for 12 months without an 
alternative medical cause or permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral 
oophorectomy). 
9.
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 or longer based on local requirements.
10. Ability to take medications orally (feeding tube is not permitted).
11. Willing and able to comply with scheduled visits and study procedures.

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Exclusion Criteria
1.
Currently receiving an investigational drug in a clinical trial or participating in any other type of 
medical research judged not to be scientifically or medically compatible with this study. If a patient is 
currently enrolled in a clinical trial involving non-approved use of a device, then agreement with the 
investigator and Taiho Medical monitor is required to establish eligibility.
2.
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.
3.
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.
4.
Treatment with any of the following within the specified time frame prior to the first dose of 
futibatinib:
a.
Major surgery within 4 weeks (surgical incision should be fully healed)
b.
Radiotherapy for extended field within 4 weeks or limited field radiotherapy within 2 weeks
c.
A drug that has not received regulatory approval for any indication within 14 or 21 days of 
treatment for a nonmyelosuppressive or myelosuppressive agent, respectively.
5.
Received strong inhibitors and inducers of CYP3A4 within 2 weeks of first dose
6.
Prior treatment with an FGFR inhibitor
7.
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 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 futibatinib administration, or may interfere 
with the interpretation of study results, and in the judgment of the Investigator would make the 
patient inappropriate for entry into this study
8.
Active central nervous system (CNS) metastasis and/or carcinomatous meningitis. Patients with 
previously treated brain metastases that are clinically and radiologically stable (for at least 4 weeks 
prior to enrollment) are eligible.
9.
Known additional malignancy that is progressing or has required active treatment within the past 
2 years. Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or 
carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially 
curative therapy are not excluded.
10. Pregnant or breastfeeding.

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Evaluation Criteria:
Efficacy
Cohorts A and B
For patients in Cohorts A and B, 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). Primary objective and additional 
secondary objectives will be assessed by an IRC.
Results of the local 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 decisions.
Cohort C
Efficacy will be assessed based on investigators’ assessment of imaging, bone marrow, peripheral blood, 
and extramedullary disease. Depending on the presentation response will be determined based on
Treatment Response Criteria for MDS/MPN (Savona et al. 2015), Response Evaluation Criteria in 
Lymphoma (RECIL 2017) (Younes et al. 2017), and International Working Group (IWG) response 
criteria for AML (Cheson et al. 2003).
A review of the response assessments will be conducted by an adjudication committee.
Safety
The assessment of safety will be based on the incidence of treatment-emergent adverse events (TEAEs)
and on-study laboratory parameters. Grading of TEAEs will be performed using NCI-CTCAE V5.0.
Pharmacokinetics
The PK population will consist of all patients who received futibatinib and have evaluable blood samples 
for analyses. 
Pharmacodynamics
Genetic aberrations will be tested using analytically validated assay on NGS or similar technology at a 
central laboratory.
A blood sample will be collected to assess FGF/FGFR aberrations in ctDNA. In addition to assessing 
ctDNA as a pharmacodynamic biomarker, samples or a set of samples will be used to verify its utility as 
an alternative to tumor tissues for the potential companion diagnostic. Samples will be collected and 
stored, as per the laboratory manual, and analyzed in batches.
Archival or fresh tumor/bone marrow samples will be collected during screening 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 after study completion for 
future testing.

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Statistical Methods:
Determination of Sample Size
Approximately 60 patients with solid tumors harboring FGFR rearrangements will be enrolled in 
Cohort A. Sample size considerations (primary endpoint ORR) are based on a 2-stage Simon design, 
comparing a poor response of ≤10% vs a promising response of ≥25%, at a 5% 1-sided significance 
level and approximate 90% power.

In Stage 1 (futility assessment), enrollment will include 35 patients and accrual will continue 
to Stage 2, if at least 4 (11.4%) of 35 patients respond (CR or PR).

In Stage 2, if the Stage 1 futility boundary is exceeded, an additional 25 patients will be 
enrolled, for a total of at least 60 patients. With a total of 60 patients, if the observed ORR is 
30%, the 95% exact confidence interval (CI) is (18.9%, 43.2%).
Approximately 35 patients with gastric or GEJ cancer harboring FGFR2 amplification will be enrolled in 
Cohort B. Sample size considerations are based on differentiating a historical control ORR of 10% or less, 
with a target ORR of 35%. Assuming the true ORR is 35%, the cohort has approximately 96% power to 
reject the null hypothesis that the true ORR is ≤10%, considering a 2-sided alpha of 5%. With a sample 
size of 35, observing at least 8 responders will have a 95% CI lower bound excluding 10% (ORR of 23% 
with 95% CI [10.4% - 40.1%]).
Approximately 20 patients with MLN harboring FGFR1 rearrangements will be enrolled in Cohort C. 
Sample size considerations are based on differentiating a historical control CR rate of 10% or less with a 
target CR rate of 50%. Assuming the true CR rate is 50%, the cohort has over 95% power to reject the 
null hypothesis that the true CR rate is ≤10%, considering a 2-sided alpha of 5%. Observing at least 
6 responders out of 20 treated patients will have a 95% CI lower bound excluding 10% (CR rate of 30% 
with 95% CI (11.9% - 54.3%).
Interim Analysis
The Sponsor will review the data at the time Cohort A has the required number of patients to determine if 
the cohort should continue.
Efficacy Analyses
Cohorts A and B
Primary Efficacy Analysis
Objective response rate is defined as the proportion of patients with objective evidence of CR or PR. The 
primary evaluation of ORR will be based on an independent central review of radiologic images. 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.
Secondary Efficacy Analyses
Overall response rate based on investigator assessment will be determined as decribed above for the 
primary analysis of ORR based on independent central review of radiologic images. 
Disease control rate will be analyzed using the same methodology as ORR.

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Duration of response will only be evaluated in patients with an 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 in a similar manner to PFS. In the absence of confirmation of death or 
for patients who are alive as of the OS cut-off date, survival time will be censored at the last known date 
that the patient was alive.
Cohort C
Primary Analysis
Complete response rate defined as the proportion of patients who achieved a CR will be calculated and 
the exact 2-sided CI will also be derived using the Clopper Pearson methodology.
Secondary Analyses
The overall response, CR+CRi (leukemia presentation only), CCyR, and PCyR rates will be calculated 
and the exact 2-sided CIs will also be derived using the Clopper-Pearson methodology.
Duration of CR (only in patients who achieved a CR), duration of CR+CRi (only in patients who 
achieved a CR/CRi [leukemia presentation only]), and duration of response (only in patients with an 
objective response of CR, CRi [leukemia presentation only], or PR) will be estimated using the Kaplan-
Meier method. 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.
Relapse-free survival will only be evaluated in patients with an objective response of CR and measured 
from the first date of achieving CR until the first date of relapsed disease or death from any cause, 
whichever occurs first. Patients who die without a reported disease relapse will be considered to have 
relapsed on the date of their death. Patients who did not relapse or die will be censored on the date of their 
last tumor assessment. Patients who started any subsequent anti-cancer therapy without a prior reported 
relapse will be censored at the last tumor assessment prior to initiation of the subsequent anti-cancer 
therapy.

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Event-free survival will be estimated only for patients with leukemia presentation using the Kaplan-Meier 
method. EFS is defined as the time from first dose of study therapy to treatment failure, relapse after CR
(if applicable), or death from any cause, whichever occurs first. For a patient with none of these events 
before the end of study follow-up, observation of EFS is censored at the date of last contact prior to the 
analysis cut-off date. If the patient does not achieve a CR, EFS is defined as the point of treatment failure 
or death, whichever comes first. Treatment failure for EFS is defined as PD in this study.
Overall survival will be analyzed in a similar manner to PFS. In the absence of confirmation of death or 
for patients who are alive as of the OS cut-off date, survival time will be censored at the last known date 
that the patient was alive.
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 V5.0, 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 futibatinib. 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 V5.0
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 
electrocardiogram findings will be presented by patient.
Pharmacodynamic and Pharmacokinetic Analyses
Pharmacodynamic and biomarker data will be summarized descriptively using all patients in the 
PD/Biomarker Evaluable Set who have evaluable data available.
PK analyses will be described in a separate Statistical Analysis Plan.

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Study Schema

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Schedule of Events
Evaluations on D1 of a cycle should be performed within 24 hours prior to dosing, unless 
otherwise noted. Procedures already performed during the screening period within 72 hours prior 
to dosing do not need to be repeated on C1D1. The End of Treatment (EOT) visit must be 
performed within 7 days after a 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). Required assessments for patients in Cohorts A and B are 
presented in Table 1 and for Cohort C in Table 2. Required assessments during the extension 
phase are presented in Table 3 for all cohorts.

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Table 3:
Schedule of Events – Study Extension Phase: All Cohorts
Treatment Period
At Least Every 3 Cycles
Safety Follow-up
30 (+7) Days After last Dose
Notes
Physical examination
X
X
Within 24 hours prior to dosing on D1
Vital signs
X
X
Heart rate, blood pressure, body temperature, and respiration rate.
Weight
X
X
Ophthalmological examination
(X)
X
As needed due to local requirements, physician judgment, and/or 
symptoms or signs of mineral deposits.
ECOG performance status
X
X
Within 24 hours prior to dosing on D1
12-Lead electrocardiogram 
X
X
Hematology and coagulation
X
X
Within 24 hours prior to dosing on D1
Chemistry (serum or plasma)
X
X
Within 24 hours prior to dosing on D1
Pregnancy test
X
More frequently if required by local regulations. 
Prior & concomitant 
medications, AE assessments
(X)
X
Collect from the time main informed consent is signed through 30 days 
after administration of the last dose of study therapy or until the start of 
new anticancer therapy, whichever is earlier.  
Tumor assessments/imaging
(X)
All Cohorts: CT/MRI scans at baseline and the end of every 2 cycles 
±7 days), or as clinically indicated, until radiologic PD or initiation of new 
anticancer therapy (whichever comes first).
Cohort C only: bone marrow, PET, and other tumor assessments as 
clinically indicated.

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TABLE OF CONTENTS
PROTOCOL SYNOPSIS ................................................................................................................2
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS................................................26
1.
INTRODUCTION......................................................................................................29
1.1.
Disease Background ...................................................................................................29
1.2.
Futibatinib (TAS-120) ................................................................................................30
1.2.1.
Clinical Overview.......................................................................................................30
1.3.
Summary of Study Rationale......................................................................................31
2.
OBJECTIVES AND ENDPOINTS............................................................................32
3.
INVESTIGATIONAL PLAN.....................................................................................34
3.1.
Overview of Study Design..........................................................................................34
3.2.
Scientific Rationale for Study Design ........................................................................35
3.3.
Study Periods and Visits for Each Patient ..................................................................35
3.3.1.
Screening Period.........................................................................................................35
3.3.2.
Treatment Period and End of Treatment Visit............................................................35
3.3.3.
Safety Follow-Up Period and 30-Day Safety Follow-Up Visit..................................35
3.3.4.
Post-Discontinuation Considerations..........................................................................36
3.3.5.
Survival Follow-up .....................................................................................................36
3.4.
Study Completion and Study Extension.....................................................................36
3.5.
Patient Enrollment ......................................................................................................36
4.
SELECTION AND WITHDRAWAL OF PATIENTS..............................................37
4.1.
Inclusion Criteria ........................................................................................................37
4.2.
Exclusion Criteria.......................................................................................................38
4.3.
Screen Failure .............................................................................................................40
4.4.
Discontinuation of Treatment.....................................................................................40
4.5.
Withdrawal from the Study ........................................................................................40
5.
STUDY TREATMENT..............................................................................................42
5.1.
Study Drug Administration.........................................................................................42
5.2.
Dose and Schedule Modifications ..............................................................................42
5.2.1.
Dose Modifications for Nonhematologic Toxicities ..................................................42
5.2.2.
Dose Modifications for Hematologic Toxicities ........................................................46
5.2.3.
Dose Modifications in Case of Induced Drug Liver Injury (Hy’s Law) ....................47

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5.3.
Treatment Compliance................................................................................................47
5.4.
Concomitant Medications and Therapies ...................................................................47
5.4.1.
Prohibited Medications and Therapies .......................................................................47
5.4.2.
Concomitant Medications and Therapies Requiring Precautions...............................47
5.4.3.
Drug Interactions ........................................................................................................48
5.5.
Effective Contraception During Study .......................................................................48
5.6.
Study Drug Materials and Management.....................................................................49
5.6.1.
Description of Study Drug..........................................................................................49
5.6.2.
Packaging and Labeling..............................................................................................49
5.6.3.
Storage ........................................................................................................................49
5.6.4.
Accountability.............................................................................................................49
6.
STUDY ASSESSMENTS ..........................................................................................50
6.1.
Ophthalmological Examination..................................................................................51
6.2.
Laboratory Assessments .............................................................................................51
7.
PHARMACOKINETICS ...........................................................................................52
8.
EFFICACY EVALUATIONS....................................................................................53
8.1.
Cohorts A and B .........................................................................................................53
8.1.1.
Efficacy Criteria..........................................................................................................53
8.1.2.
Method of Imaging .....................................................................................................53
8.1.3.
Tumor Definitions ......................................................................................................54
8.1.4.
Response Criteria........................................................................................................55
8.1.4.1.
Target and Non-Target Response Assessments..........................................................55
8.1.4.2.
Additional Criteria to Consider When Making Tumor Response Assessments.........56
8.1.5.
Objective Response Assessment.................................................................................57
8.2.
Cohort C......................................................................................................................58
8.2.1.
Efficacy Criteria..........................................................................................................58
8.2.2.
Response Criteria........................................................................................................58
8.2.3.
Response Definitions..................................................................................................58
8.3.
Efficacy Endpoints......................................................................................................60
9.
SAFETY EVALUATIONS........................................................................................61
9.1.
Adverse Events ...........................................................................................................61
9.2.
Reporting of Adverse Events......................................................................................61
9.2.1.
Terms of Reported Adverse Events............................................................................61

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9.2.2.
Severity of Adverse Events ........................................................................................61
9.2.3.
Causal Relationship with Study Drug.........................................................................61
9.2.4.
Outcome of Adverse Events.......................................................................................62
9.2.5.
Follow-up of Adverse Events .....................................................................................62
9.3.
Laboratory Assessments .............................................................................................63
9.3.1.
Reporting and Evaluation of Laboratory Test Results ...............................................63
9.3.2.
Repeat Testing ............................................................................................................63
9.4.
Serious Adverse Events..............................................................................................63
9.4.1.
Definitions of Serious Adverse Events.......................................................................63
9.4.2.
Reporting of Serious Adverse Events (within 24 hours)............................................64
9.4.3.
Reporting of Deaths (within 24 hours).......................................................................64
9.5.
Other Safety Information............................................................................................64
9.5.1.
Pregnancy ...................................................................................................................64
9.5.2.
Overdose.....................................................................................................................65
10.
BIOMARKER EVALUATION .................................................................................66
10.1.
Biomarker Assessments..............................................................................................66
10.1.1.
Objectives and Background........................................................................................66
10.1.2.
Assessment of FGF/FGFR Aberrations in Blood ......................................................66
10.1.3.
Tissue Samples ...........................................................................................................66
10.2.
Sample Storage and Disposal .....................................................................................66
10.3.
Analytical Procedures.................................................................................................66
11.
STATISTICAL CONSIDERATIONS .......................................................................67
11.1.
Estimation of Sample Size..........................................................................................67
11.2.
Planned Interim Analysis............................................................................................68
11.3.
Analysis Populations ..................................................................................................68
11.4.
Criteria for Handling of Patient Data..........................................................................68
11.5.
Statistical Analyses.....................................................................................................68
11.5.1.
Demographic and Baseline Characteristics ................................................................68
11.5.2.
Study Drug Administration.........................................................................................69
11.5.3.
Efficacy Analyses .......................................................................................................69
11.5.3.1.
Cohorts A and B .........................................................................................................69
11.5.3.2.
Cohort C......................................................................................................................70
11.5.4.
Safety Analyses ..........................................................................................................71

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11.5.5.
Pharmacokinetic Analysis ..........................................................................................71
11.5.6.
Pharmacodynamic/Biomarker Analysis .....................................................................72
12.
ADMINISTRATIVE CONSIDERATIONS ..............................................................73
12.1.
Protocol Compliance ..................................................................................................73
12.2.
Protocol Deviations ....................................................................................................73
12.3.
Protocol Amendments ................................................................................................73
12.4.
Study Termination ......................................................................................................73
12.5.
Case Report Forms .....................................................................................................73
12.6.
Access to Source Data/Documents.............................................................................73
12.6.1.
Source Data/Documents .............................................................................................74
12.6.2.
Access to Source Data ................................................................................................74
12.7.
Data Handling.............................................................................................................74
12.8.
Responsibilities of Recordkeeping .............................................................................74
12.8.1.
Investigator and Study Site.........................................................................................74
12.8.2.
Sponsor .......................................................................................................................75
12.9.
Monitoring..................................................................................................................75
12.10.
Financial Disclosure ...................................................................................................75
12.11.
Compensation for Health Injury.................................................................................75
12.12.
Study Administrative Structure ..................................................................................75
13.
QUALITY CONTROL AND QUALITY ASSURANCE .........................................76
13.1.
Quality Control ...........................................................................................................76
13.2.
Quality Assurance.......................................................................................................76
14.
ETHICS ......................................................................................................................77
14.1.
Ethical Conduct of the Study......................................................................................77
14.2.
Written Informed Consent..........................................................................................77
14.3.
Institutional Review Board/Independent Ethics Committee ......................................77
15.
PUBLICATION POLICY ..........................................................................................78
15.1.
Publication Policy.......................................................................................................78
15.2.
Secondary Use of Data ...............................................................................................78
16.
REFERENCES ...........................................................................................................79
APPENDIX A.
ECOG PERFORMANCE..................................................................................82
APPENDIX B.
DIETARY GUIDELINES FOR TREATMENT OF 
HYPERPHOSPHATEMIA ........................................................................................83

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APPENDIX C.
CLASSIFICATION OF SUBSTRATES, INHIBITORS, AND 
INDUCERS OF CYP ENZYMES AND TRANSPORTERS ....................................84

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LIST OF TABLES
Table 1: 
Schedule of Events (Cohorts A and B).......................................................................14
Table 2: 
Schedule of Events (Cohort C)...................................................................................16
Table 3:
Schedule of Events – Study Extension Phase: All Cohorts........................................19
Table 4:
Objectives and Endpoints (Cohorts A and B).............................................................32
Table 5:
Objectives and Endpoints: Cohort C ..........................................................................33
Table 6:
Dose Modifications for Related Nonhematologic Toxicities....................................43
Table 7:
Dose Modifications for Related Ocular Toxicities....................................................44
Table 8:
Recommendations for Hyperphosphatemia Management..........................................45
Table 9:
Futibatinib Dose Interruption and Modification Criteria for Related 
Hematologic Toxicities for Patients in Cohorts A and B ...........................................46
Table 10:
Pharmacokinetic Blood Sample Collection................................................................52
Table 11:
Target and Non-target Lesions ...................................................................................56
Table 12:
Time Point Response for Patients with Target (±Non-target) Disease.......................57
Table 13:
Time Point Response for Patients with Only Non-target Disease..............................57
Table 14:
Response Definitions for Cohort C.............................................................................59
Table 15:
Efficacy Endpoints......................................................................................................60
Table 16:
Observed ORR with Exact 95% Confidence Interval (Cohort A)..............................67
Table 17:
Observed ORR with Exact 95% Confidence Interval (Cohort B)..............................67
Table 18:
Observed CR Rate with Exact 95% Confidence Interval (Cohort C) ........................68
Table 19
Definitions of Analysis Populations..........................................................................68
LIST OF FIGURES
Figure 1:
Study Schema .............................................................................................................34

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Abbreviation
Definition
AE
Adverse event
ANC
Absolute neutrophil count
ALT
Alanine aminotransferase
ASCO
American Society of Clinical Oncology
AST
Aspartate aminotransferase
BCR
Breakpoint cluster region (gene)
BCRP
Breast cancer resistance protein
CCA
Cholangiocarcinoma
CI
Confidence interval
CR
Complete response
CCyR
Complete cytogenetic response
CrCl
Creatinine clearance
CRi
Complete response with incomplete hematological recovery
CT
Computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
ctDNA
Circulatng tumor DNA
CYP
Cytochrome P450
DCR
Disease control rate
DOR
Duration of response
ECOG
Eastern Cooperative Oncology Group
eCRF
Electronic case report form

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Abbreviation
Definition
EFS
Event-free survival
EOT
End of treatment/end of therapy
FGFR
Fibroblast growth factor receptor
FISH
Fluorescence in situ hybridization
GEJ
Gastro-esophageal junction
GCP
Good Clinical Practice
HSCT
Hematological stem cell transplant
iCCA
Intrahepatic cholangiocarcinoma
ICF
Informed consent form
ICH
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use
IEC
Independent Ethics Committee
IND
Investigational New Drug
IRB
Institutional Review Board
IRC
Independent Central Review Committee
MLN
myeloid/lymphoid neoplasms
MRI
Magnetic resonance imaging
NCI
National Cancer Institute
NGS
Next generation sequencing
ORR
Objective response rate
OS
Overall survival
PCyR
Partial cytogenetic response
PD
Progressive disease

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Abbreviation
Definition
PFS
Progression free survival
P-gp
P-glycoprotein
PK
Pharmacokinetic(s)
popPK
Population pharmacokinetics
PR
Partial response
RECIL
Response Evaluation Criteria in Lymphoma
RECIST 1.1
Response Evaluation Criteria in Solid Tumors, Version 1.1
RFS
Relapse-free survival
QD
Once daily
QTcF
QT interval corrected for heart rate using Fridericia’s formula
SAE
Serious adverse event
SAP
Statistical analysis plan
SD
Stable disease
SOP
Standard operating procedure
TEAE
Treatment-emergent adverse event
TOI
Taiho Oncology, Inc.
ULN
Upper limit of normal
WHO
World Health Organization
WOCBP
Women of childbearing potential

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1.
INTRODUCTION
Futibatinib is a novel and selective small molecule irreversible, covalent inhibitor of fibroblast 
growth factor receptor (FGFR) 1–4 that is currently being tested in patient with different cancers. 
Evolving knowledge of the molecular and genetic basis of cancer has led to refinements in the 
categorization of malignancies based on molecular markers. This, in turn, has led to changes in 
trial design, specifically tumor agnostic trials that enroll patients with the same genetic 
alterations but not the same histologic or anatomic tumor type. These trials are important because 
they provide insight into the importance of a genomic alteration across various histologic tumor 
types and allow for the development of more targeted therapies (Lacombe et al 2014).
1.1.
Disease Background
FGFR signaling plays a crucial role in cancer cell proliferation, migration, angiogenesis, and 
survival. Recent studies have uncovered increasing evidence that deregulated FGFRs can 
function as driving oncogenes in certain tumor types, maintaining the malignant properties of 
cancer cells (Turner & Grose 2010). When FGFRs are amplified, rearranged, or undergo fusion, 
aberrant activation of downstream pathways results in mitogenic, mesenchymal, and 
antiapoptotic responses in cells. Therefore, FGFRs are attractive targets for therapeutic 
intervention in cancer (Turner & Grose 2010).
FGFR aberrations were found in 7.1% of cancers, with the majority being gene amplifications
(66%), followed by mutations (26%) and rearrangements (8%) (Helsten et al. 2016).
Although they are rare, FGFR2 fusions with multiple partners have been uncovered in many 
types of cancer, including cholangiocarcinoma (CCA), lung cancer, thyroid cancer, breast 
cancer, and prostate cancer (Wu et al. 2013; Gallo et al. 2015; Yoshihara et al. 2015). Of all the 
FGFRs, FGFR2 shows the broadest range of fusion partners. Fusion genes have also been 
reported in bladder cancer and urothelial carcinoma (Williams et al. 2013; Loriot et al. 2019). It 
is clear that FGFR fusions are emerging as a new class of targetable fusions in solid tumors.
Amplification of FGFR2 has been described in 4-10% of gastric cancer, particularly of the 
aggressive diffuse subtype (Deng et al. 2012; Kunii et al. 2008; Jung et al. 2012; Liu et al. 2014). 
Each year, approximately 990,000 people are diagnosed with gastric cancer worldwide, and 
about 738,000 people die from this disease (Ferlay et al. 2010), making gastric cancer the fourth
most common cancer and the second most common cause of cancer death (Jemal et al. 2010). 
While the incidence of gastric cancer has been decreasing, the incidence of gastro-esophageal 
junction (GEJ) cancer doubled in Western countries from the 1970s to the 1990s, with rates 
stabilizing today (Buas & Vaughan, 2013).
In vitro, FGFR2-amplified gastric cancer cell lines have been shown to be selectively sensitive to 
the inhibitory effects of FGFR tyrosine kinase inhibitors (Kunii et al. 2008).
Myeloid and lymphoid neoplasms with abnormalities of the FGFR1 gene have been recognized 
as a distinct disease group in the 2008 World Health Organization (WHO) classification of 
hematopoietic neoplasms (Bain et al. 2008). These myeloproliferative neoplasms are 
characterized by eosinophilia, lymphadenopathy, and a high incidence of T-cell non-Hodgkin 
lymphoma with progression to acute myeloid leukemia (MacDonald et al. 1995). They occur 
over a wide age range of 3 to 84 years, with a median of 44 years, and with a very slight male 

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predominance (male to female ratio of 1.2:1) (Jackson et al. 2010). This is a very rare disease, 
with fewer than 100 patients reported around the world (MacDonald et al. 2002; 
Jackson et al. 2010). There is a marked absence of curative treatments for these patients. Of the 
4 FGFRs, FGFR2 and FGFR3 have been identified as having comparatively more frequent gene 
rearrangements (Courjal et al. 1997). However, although hematopoietic neoplasms with FGFR1 
rearrangements are uncommon entities, they are extremely aggressive and resistant to standard 
treatments. One of the most frequently observed cytogenetic abnormalities is t(8;22) 
(p11.2;q11.2). The t(8;22) abnormality results in an in-frame fusion of FGFR1 on 8p11 and the 
breakpoint cluster region (BCR) gene on 22q11. The resultant fusion proteins activate tyrosine 
kinases, which may result in the development of hematologic malignancies 
(Villafuerte-Gutiérrez et al. 2018).
This Phase 2 clinical trial will investigate the efficacy, safety, tolerability, pharmacokinetics 
(PK), and pharmacodynamics of futibatinib in patients with tumors harboring specific FGFR 
aberrations. Patients will be enrolled into one of 3 cohorts: patients with solid tumors harboring
FGFR rearrangements (excluding primary brain tumors and intrahepatic CCA [iCCA]); patients 
with gastric or GEJ cancer harboring FGFR2 amplification; and patients with myeloid or 
lymphoid neoplasms (MLN) harboring FGFR1 rearrangement.
1.2.
Futibatinib (TAS-120)
1.2.1.
Clinical Overview
As of 5 September 2019, a total of 460 subjects (41 healthy volunteers and 419 patients) have 
been treated with futibatinib across 4 clinical trials. 

Study 10059010 is an ongoing, Phase 1 study being conducted in Japan to evaluate the 
PK, safety, and preliminary efficacy of futibatinib in patients with advanced solid tumors
administered futibatinib three times a week (doses 8 to 240 mg) or daily (QD, doses 8 to 
120 mg). The most frequently reported treatment-emergent AEs (>20% of all patients at 
all dose levels) were hyperphosphatemia, decreased appetite, diarrhea, constipation, 
nausea, stomatitis, and vomiting. Adverse events were mainly Grade 1 or 2.

Study TAS-120-101 is an ongoing, 3-part global study to evaluate the PK, safety, and 
efficacy of futibatinib administered 3 times a week (doses 8 to 200 mg) or QD (doses 4 to 
24 mg): 
o
Phase 1 Dose Escalation (completed with a total of 86 patients receiving either 
daily or 3-times-per-week dosing)
o
Phase 1 Dose Expansion, which includes additional cohorts in CCA, gliomas, 
urothelial carcinoma, and basket cohorts with FGF/FGFR aberrations
o
Phase 2 study initiated in April 2018, evaluating futibatinib at a QD dose of 
20 mg, in patients with iCCA harboring FGFR2 gene rearrangements 
o
The most frequently reported treatment-emergent AEs (>20%) in patients 
administered futibatinib 20 mg QD (recommended Phase 2 dose) were 
hyperphosphatemia, diarrhea, constipation, nausea, dry mouth, increased ALT, 
increased AST, and fatigue.

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
Study 10059020, a Phase 1, PK, and bioequivalence study in healthy adult males. This 
completed study compared two futibatinib formulations and found them to be 
biologically equivalent. 

Study TAS-120-102, a food effect study in healthy adult subjects. This completed study 
evaluated the effect of food on the PK of futibatinib under fasting or fed conditions and 
demonstrated that PK was affected by the consumption of a high-fat, high-calorie meal.
Efficacy has been observed in different tumor types:

Solid tumors harboring FGFR rearrangements, including iCCA, head and neck, 
unknown primary, and gastric cancer

Gastric cancer with FGFR2 amplification

MPN with FGFR1 rearrangement

Other solid tumors with different FGFR aberrations
Refer to the Investigator’s Brochure for more detailed background information on futibatinib.
1.3.
Summary of Study Rationale
Based on available preclinical and clinical data to date, the Sponsor concludes that the benefit-
risk assessment results of futibatinib support the continued enrollment and treatment of patients 
in clinical trials and supports further investigation of futibatinib in tumors with FGFR 
aberrations.
The Phase 2 study described in this protocol will evaluate the efficacy and safety of futibatinib in 
patients with FGFR aberrations in 3 distinct cohorts.
Based on prior safety and efficacy experience in the broad Phase I dose escalation and expansion 
study a dose of 20 mg QD of futibatinib has been selected for use in this Phase 2 trial. The drug 
is administered continuously without interruption. Treatment cycles of 28 days will be used to 
define the protocol specified interval for tumor measurement and other interventions.

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2.
OBJECTIVES AND ENDPOINTS
The objectives and endpoints of this study are shown in Table 4 and Table 5. 
Table 4:Objectives and Endpoints (Cohorts A and B)
Primary
To evaluate the objective response rate (ORR) 
in patients with solid tumors harboring FGFR
rearrangements or gastric cancer (including 
GEJ cancer) harboring FGFR2 amplifications 
based on independent central review of 
radiologic images (IRC)
ORR, defined as the proportion of patients experiencing a best 
overall response of partial response (PR) or complete response 
(CR) (per Response Evaluation Criteria in Solid Tumors, 
Version 1.1 [RECIST 1.1]), based on IRC
Secondary 

To evaluate ORR based on investigator 
assessment

To evaluate progression-free survival 
(PFS), disease control rate (DCR), 
duration of response (DOR), and overall 
survival (OS)

To assess safety and tolerability

ORR, defined as the proportion of patients experiencing a 
best overall response of partial response of PR or CR (per 
RECIST 1.1), based on investigator assessment

DCR, defined as the proportion of patients experiencing a 
best overall response of stable disease (SD), PR, or CR (per 
RECIST 1.1), based on IRC 

DOR defined as the time from the first documentation of 
response (CR or PR per RECIST 1.1 based on IRC) to the 
first documentation of objective tumor progression or death 
due to any cause, whichever occurs first

PFS, defined as the time from first dose of study therapy to 
the date of death (any cause) or disease progression (based 
on IRC), whichever occurs first

OS, defined as the time from the date of first dose to the 
death date

Safety based on reported AEs and on-study laboratory
parameters, graded according to the National Cancer 
Institute—Common Terminology Criteria for Adverse 
Events, Version 5.0 (NCI-CTCAE V5.0), 
Exploratory 

To assess the possible impact of genetic 
alterations or other laboratory 
abnormalities on the efficacy of 
futibatinib 

To assess the population 
pharmacokinetics (popPK) and exposure 
response

Assessment of pharmacodynamic effects will be analyzed 
from circulating tumor DNA (ctDNA), tumor biopsy, and/or 
plasma samples.

PopPK and exposure response will be analyzed from blood 
samples collected during treatment.

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Table 5:Objectives and Endpoints: Cohort C
Overall Objective
The overall objective of Cohort C is to assess the clinical activity of futibatinib as monotherapy in the treatment of 
patients with MLN harboring FGFR1 rearrangements.
Primary
To evaluate complete response (CR) rate 
CR rate, defined as the proportion of patients who achieved a CR.
Secondary 

To evaluate:
o
ORR
o
CR + complete response with 
incomplete hematological recovery 
(CRi) rate 
o
Complete or partial cytogenetic 
responses (CCyR or PCyR) rate
o
Duration of CR
o
Duration of CR+CRi
o
DOR
o
Time-to-events 

To assess the safety and tolerability

ORR, defined as the proportion of patients who achieved a 
CR, CRi, or PR

CR+CRi rate, defined as the proportion of patients who 
achieved a CR or CRi 

CCyR rate, defined as the proportion of patients who 
achieved CCyR

PCyR rate, defined as the proportion of patients who achieved 
PCyR

Duration of CR defined as the time from the first 
documentation of CR to the first documentation of objective 
tumor progression or death due to any cause, whichever 
occurs first

Duration of CR+CRi defined as the time from the first 
documentation of CR/CRi to the first documentation of 
objective tumor progression or death due to any cause, 
whichever occurs first

DOR defined as the time from the first documentation of CR, 
CRi, or PR to the first documentation of objective tumor 
progression or death due to any cause, whichever occurs first 

PFS, defined as the time from first dose of study therapy to 
the date of death (any cause) or disease progression, 
whichever occurs first

Relapse-free survival (RFS), defined as the time from the first 
documentation of CR to the first documentation of disease 
relapse or death due to any cause, whichever occurs first. 

Event-free survival (EFS) (leukemia presentation only), 
defined as the time from first dose of study therapy to 
treatment failure, disease relapse after CR, or patient death 
from any cause. 

OS, defined as the time from the date of first dose to the death 
date. 

Safety based on reported AEs and on-study laboratory 
parameters, graded according to the NCI-CTCAE V5.0.
Exploratory

To assess the pharmacodynamic effects of 
treatment with futibatinib

To assess the association of response and 
mechanisms of resistance in tumor tissue 
biopsies and/or blood

To assess the popPK and exposure 
response

Changes in pharmacodynamic markers assessed in bone 
marrow tissue biopsies.

Exploratory association of tissue and/or blood markers with 
tumor efficacy endpoints and/or tumor resistance to 
futibatinib.

PopPK and exposure response will be analyzed from blood 
samples collected during treatment

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3.
INVESTIGATIONAL PLAN
3.1.
Overview of Study Design
Study TAS-120-202 is an open-label, multinational, 3-arm Phase 2 study evaluating the efficacy, 
safety, tolerability, PK, and pharmacodynamics of futibatinib in patients with FGFR aberrations. 
Eligible patients will be assigned to 1 of 3 treatment cohorts based on diagnosis and FGFR gene 
aberration status (Figure 1):
Figure 1:
Study Schema
Patients will receive futibatinib at an oral dose of 20 mg once a day on a continuous 28-day 
cycle.
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 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, the patient withdraws consent, or the study is 
terminated early by the Sponsor.

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Additional cohorts may be added in the future in case of new emerging data. This change will be 
implemented through a protocol amendment which will describe the rationale for the addition(s).
3.2.
Scientific Rationale for Study Design
Please see Section 1.3.
3.3.
Study Periods and Visits for Each Patient
The study periods / visits described in this section are defined for all patients. Please see the 
schedule of events for an outline of all assessments to be performed during each study period / 
visit.
For all patients, the Safety Assessment Period begins at the time the informed consent form 
(ICF) is signed and continues until at least 30 days after the last dose of futibatinib. After the 
30-day Safety Follow-Up Visit (see below), patients who have not started treatment with a new 
anti-cancer therapy will be assessed for drug-related serious adverse events (SAEs) only.
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).
3.3.1.
Screening Period
The Screening Period is defined as the time from when the patient signs the ICF to when they 
receive the first dose of futibatinib. Determination of eligibility is based on the entry criteria 
enumerated in Section 4. No protocol-specific procedures or assessments may be performed 
prior to completion of the ICF, except for procedures that represent standard-of-care.
3.3.2.
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 first dose of futibatinib (Day 1) to the date of last dose of futibatinib. An 
end-of-treatment (EOT) visit must be performed within 7 days after the decision is made to 
discontinue futibatinib; at this visit, every effort should be made to perform the assessments 
outlined in the schedule of events. 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.
3.3.3.
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 (+7 days) following the last 
dose of study therapy. If the patient starts new anticancer therapy within 30 days of the last dose 
of study therapy, 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 the 
schedule of events. 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 Follow-Up Visit (see below), patients who have not started treatment 
with a new anti-cancer therapy will be assessed for drug-related serious adverse events (SAEs)
only.

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3.3.4.
Post-Discontinuation Considerations
Patients who discontinue without documented disease progression should continue to undergo 
tumor assessments according to the Schedule of Events (that is, every 8 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).
3.3.5.
Survival Follow-up
Once a patient discontinues study treatment, regardless of the reason, survival follow-up will 
begin, unless the patient withdraws consent or the study is terminated early by the Sponsor.
During this period, the patient or family should be contacted for survival follow-up every 
12 weeks (±2 weeks) until survival events (deaths) have been reported for 75% of enrolled 
patients, patient withdraws consent or the study is terminated early by the Sponsor. In addition, 
all subsequent anticancer treatments will be recorded.
3.4.
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.
Following Study Completion, patients deriving benefit from study therapy in the opinion of the 
Investigator and Sponsor may be permitted to continue treatment with futibatinib in a Study 
Extension phase. During Study Extension, patients may receive treatment until withdrawal 
criteria are met and study drug is available.  
During this period, all safety assessments are to be continued according to the schedule in 
(Table 3). Specifically, study extension data collection is to include, at a minimum:

Study drug administration;

Study drug accountability;

Serious adverse events;

Non-serious AEs that are related to study treatment or result in treatment 
discontinuation; and

Any cases of pregnancy or overdose.
3.5.
Patient Enrollment
Eligibility must be verified prior to patient enrollment. Patients will be enrolled via an Interactive 
Voice/Web Response System (IXRS). The patient should receive the first dose of study therapy 
within 3 days following enrollment.

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4.
SELECTION AND WITHDRAWAL OF PATIENTS
Results of FGFR gene aberration status should be available before the patient undergoes any 
protocol-specific procedures. 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 participation in this 
study:
1. Provide written informed consent
2. ≥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. Has recovered from the acute toxic effects of prior anticancer therapy to baseline or 
Grade 1 (except toxicities which are not clinically significant such as alopecia)
5. Known FGFR aberration status and tumor type that meet all of the criteria for 1 of the 
following cohorts:
a. Cohort A
i.
Histologically-confirmed, locally-advanced, advanced, or metastatic solid tumors
harboring a FGFR1-4 rearrangement determined in tumor tissue using next-
generation sequencing (NGS), fluorescence in situ hybridization (FISH), or other 
assays that can determine gene rearrangements in tumor tissues. Patients with primary 
brain tumor or intrahepatic cholangiocarcinoma are not eligible.
ii. Measurable disease per RECIST 1.1
iii. Had disease progression/recurrence after standard treatment for their advanced or 
metastatic cancer 
b. Cohort B
i.
Histologically-confirmed, locally-advanced, advanced, or metastatic gastric or GEJ 
cancer harboring a FGFR2 amplification. The tumor must have an FGFR2/CEN10
ratio of ≥5 or an FGFR2 copy number ≥10 signals per cell determined in tumor tissue 
using NGS, FISH, or other assays that can determine gene amplifications in tumor 
tissues.
ii. Measurable disease per RECIST 1.1
iii. Received at least 2 prior systemic regimens for advanced/metastatic disease
iv. Experienced disease progression/recurrence during or after the most recent prior 
systemic treatment for advanced/metastatic gastric or GEJ cancer
c.
Cohort C
i.
Confirmed MLN with a FGFR1 rearrangement as defined by WHO criteria 
ii. Not a candidate for hematological stem cell transplant (HSCT) or relapsed after 
HSCT and donor lymphocyte infusion, and progressed and not a candidate for other 
therapies. 
6. Has archival or fresh tumor tissue (preferably in block format) available to send to central 
laboratory.
7. Adequate organ function as defined by the following criteria:

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a. Cohorts A and B:
i.
Absolute neutrophil count (ANC) ≥ 1.0 × 109/L
ii. Platelet count ≥ 75,000/mm3 (≥ 75 × 109/L) 
iii. Hemoglobin ≥9.0 g/dL
iv. ALT and aspartate aminotransferase (AST) ≤3.0 × upper limit of normal (ULN); if 
liver function abnormalities are due to underlying liver metastasis, AST and ALT 
≤5.0 × ULN.
v. Total bilirubin ≤ 1.5 × ULN, or ≤ 3.0 × ULN for patients with Gilbert’s syndrome.
vi. Creatinine clearance (CrCl) (calculated or measured value): ≥40 mL/min.  For 
calculated CrCl, use the Cockcroft-Gault formula (Section 6).
vii. Phosphorus < 1.5 ULN
b. Cohort C
i.
ALT and AST ≤3.0 × ULN; if liver function abnormalities are due to underlying 
liver metastasis, AST and ALT ≤5.0 × ULN.
ii. Total bilirubin ≤ 1.5 × ULN, or ≤ 3.0 × ULN for patients with Gilbert’s syndrome.
iii. CrCl (calculated or measured value): ≥40 mL/min. For calculated CrCl, use the 
Cockcroft-Gault formula (Section 6).
iv. Phosphorus <1.5 ULN
8. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test 
prior to administration of the first dose of futibatinib. Female patients are not considered 
to be of child-bearing potential if they are post-menopausal (no menses for 12 months 
without an alternative medical cause) or permanently sterile (hysterectomy, bilateral 
salpingectomy, or bilateral oophorectomy).
9. 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 or longer based 
on local requirements.
10. Ability to take medications orally (feeding tube is not permitted).
11. 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 participation in 
this study:
1. Currently receiving an investigational drug in a clinical trial or participating in any other 
type of medical research judged not to be scientifically or medically compatible with this 
study. If a patient is currently enrolled in a clinical trial involving non-approved use of a 
device, then agreement with the investigator and Taiho Medical monitor is required to 
establish eligibility.
2. 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.

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c.
Retinal or corneal disorder confirmed by retinal/corneal examination and considered 
clinically significant in the opinion of the Investigator.
3. 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.
4. Treatment with any of the following within the specified time frame prior to the first dose 
of futibatinib:
a.
Major surgery within 4 weeks (surgical incision should be fully healed)
b. Radiotherapy for extended field within 4 weeks or limited field radiotherapy within 
2 weeks
c.
A drug that has not received regulatory approval for any indication within 14 or 
21 days of treatment for a nonmyelosuppressive or myelosuppressive agent, 
respectively
5. Received strong inhibitors and inducers of CYP3A4 within 2 weeks
6. Prior treatment with an FGFR inhibitor
7. 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 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 
futibatinib administration, or may interfere with the interpretation of study results, 
and in the judgment of the Investigator would make the patient inappropriate for entry 
into this study
8. Active central nervous system (CNS) metastasis and/or carcinomatous meningitis. 
Patients with previously treated brain metastases that are clinically and radiologically 
stable (for at least 4 weeks prior to enrollment) are eligible.
9. Known additional malignancy that is progressing or has required active treatment within 
the past 2 years. Patients with basal cell carcinoma of the skin, squamous cell carcinoma 
of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have 
undergone potentially curative therapy are not excluded.
10. Pregnant or breastfeeding.

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4.3.
Screen Failure 
Screen failures are defined as patients who consent to participate in 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 respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility criteria, 
and any SAE 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 3 times. Rescreened patients should be assigned the same subject 
identification code as for the initial screening.
4.4.
Discontinuation of Treatment
A patient will be discontinued from all study therapy for any of the following reasons: 
1. Disease progression
2. 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 2 dose reductions outlined in this protocol
3. 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
4. Pregnancy
5. Termination of the study by the Sponsor, or
6. At the patient’s request at any time irrespective of the reason. 
Patients who withdraw consent for further treatment 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 assessments, the patient should be considered to have discontinued the
study as described in Section 4.5.
4.5.
Withdrawal from the Study
A patient will be withdrawn from all study interventions and assessments (that is, discontinued 
from the study without follow-up) for any of the following reasons: 
1. Death
2. Lost to follow-up

A participant will be considered lost to follow-up if he or she repeatedly fails to 
return for scheduled visits and is unable to be contacted by the study site.

The following actions must be taken if a patient fails to return to the clinic for a 
required study visit:

The site must attempt to contact the patient and reschedule the missed visit as 
soon as possible and counsel the patient on the importance of maintaining the 

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assigned visit schedule and ascertain whether or not the patient wishes to and/or 
should continue in the study.

Before a patient is deemed lost to follow up, the Investigator or designee must 
make every effort to regain contact with the patient (where possible, 3 telephone 
calls and, if necessary, a certified letter to the patient’s last known mailing address 
or local equivalent methods). These contact attempts should be documented in the 
patient’s medical record.

Should the patient continue to be unreachable, he/she will be considered to have 
withdrawn from the study.
3.
Patient withdrawal of consent to further follow-up assessments, irrespective of the 
reason.

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5.
STUDY TREATMENT
5.1.
Study Drug Administration
A study cycle is defined as 28 days. Futibatinib is supplied as 4 mg tablets and will be taken 
orally at a dose of 20 mg daily until the patient meets any of the administration discontinuation 
criteria (see Section 4.4).
Futibatinib should be administered under fasting conditions. It should be taken with a glass of 
water, on an empty stomach, at the same time each day. No food should be consumed for 2 hours 
prior and 1 hour after the dose of futibatinib, but patients may drink water during this period.
When a PK sample is collected, futibatinib should be administered on site after collection of the 
first PK sample.
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.
5.2.
Dose and Schedule Modifications 
Stepwise dose reductions of 4 mg to 16 mg (first reduction) and 12 mg (second reduction) are 
permitted based on toxicities. If dose reduction fails to result in achieving the minimal criteria to 
resume treatment or, if toxicities occur which would necessitate reduction of the dose of 
futibatinib below 12 mg QD, the patient should be discontinued from futibatinib. 
Following a dose reduction, if a benefit/risk assessment favors an increase of futibatinib dose up 
to the initial starting dose (20 mg QD), an agreement with the Sponsor’s medical monitor is 
required prior to the dose increase. 
If toxicities related to the dose reduction do not recover based on the criteria defined below
within 28 days after the last dose of futibatinib, the patient will be discontinued permanently 
from treatment (Section 4.4). If resumption criteria are met within 28 days of the last dose of 
futibatinib, the patient may resume futibatinib treatment at the appropriate dose level.
5.2.1.
Dose Modifications for Nonhematologic Toxicities
Dosing modification guidelines for nonhematologic and ocular toxicities are provided in Table 6
and Table 7, respectively.
Recommendations for hyperphosphatemia management are provided in Table 8. These are 
suggested guidelines based on emerging data from studies evaluating FGFR inhibitors and 
studies of futibatinib.

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Table 6:
Dose Modifications for Related Nonhematologic Toxicities
Gradea
Dose 
Interruption/Resumption
Dose Adjustment
Grade 1 or 2
Maintain treatment at the same 
dose level
None
Grade 3
Withhold treatment until 
return to baseline or Grade ≤1
Reduce by 1 dose level from the previous level.
For Grade 3 nausea, vomiting, and/or diarrhea lasting 
>72 hours despite optimal medical management require 
withhold of treatment and dose reduction by one level,
Grade 4 
Discontinue treatment 
Permanent discontinuation of futibatinib.
Grade 4 (lab 
abnormality AE)
Withhold treatment until 
return to baseline or Grade ≤1
Futibatinib 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, 
futibatinib should first be held until toxicity returns to 
baseline or Grade ≤1.
Abbreviations: AE=adverse event; ALT=alanine aminotransferase; AST=aspartate aminotransferase. 
a Interrupt futibatinib if any toxicities are intolerable, regardless of the grade (including Grade 1 and 2). If or when 
the toxicity resolves to a tolerable state, consideration can be given to resuming futibatinib at the same dose if 
deemed appropriate or reduced by one dose level if needed.

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Table 7:
Dose Modifications for Related Ocular Toxicities
Grade and Definition
Study Drug Managementa
Grade 1
If there is no evidence of ocular toxicity on ophthalmologic examination, continue 
futibatinib therapy at the same dose level.
If diagnosis from ophthalmologic examination is keratitis or retinal abnormality 
such as central serous retinopathy (CSR)/ retinal pigment epithelial detachments 
(RPED), withhold futibatinib until signs and symptoms have resolved.
If toxicity is reversible (complete resolution or stabilization and asymptomatic) in 
4 weeks according to ophthalmologic examination, resume futibatinib therapy at 
the next lower dose level after consultation with the medical monitor.
Monitor for recurrence every 1 to 2 weeks for a month and as clinically 
appropriate thereafter. If there is no recurrence then re-escalation can be 
considered in consultation with the medical monitor.
Grade 2 
Withhold futibatinib therapy.
If there is no evidence of drug-related corneal or retinal pathology on 
ophthalmologic examination, withhold futibatinib until signs and symptoms have 
resolved. Resume futibatinib therapy at the next lower dose level.
If diagnosis from ophthalmologic examination is keratitis or retinal abnormality, 
withhold futibatinib until signs and symptoms have resolved or stabilized.
If toxicity is Grade 2 and reversible (complete resolution or stabilization and 
asymptomatic) within 4 weeks according to ophthalmologic examination, resume 
futibatinib therapy at the next lower dose level after consultation with the medical 
monitor.
Monitor for recurrence every 1 to 2 weeks for a month and as clinically 
appropriate thereafter. If there is no recurrence then re-escalation can be 
considered in consultation with the medical monitor.
Grade 3 
If the toxicity is Grade 3, report as a serious adverse event and permanently 
discontinue futibatinib. If, however, the toxicity is Grade 3 and reversible 
(complete resolution or stabilization and asymptomatic) within 4 weeks and the 
subject is having clinical benefit, and the investigator and the sponsor’s medical 
monitor agree that re-starting drug is in the best interest of the patient, then 
futibatinib therapy may be resumed at 2 dose levels lower if appropriate. Monitor 
for recurrence using appropriate investigations every 1 to 2 weeks for a month and 
as clinically appropriate thereafter.
For cases of recurrence consider permanent discontinuation.
Grade 4
Permanently discontinue treatment with futibatinib.
Report as a serious adverse event and monitor resolution of the event until 
complete resolution, stabilization, or the patient is lost to follow-up or withdraws 
consent (which ever happens first).
a If a patient has been deriving benefit from treatment, and the investigator can demonstrate that re-introduction of study drug is 
in the best interest of the patient considering the terminal nature of the disease, the drug may be re-introduced at a lower dose 
and/or intensity if the Medical Monitor is in agreement with this assessment. With appropriate re-consenting, the patient can be 
retreated with a 1- or 2-dose level reduction as appropriate, along with appropriate clinical follow-up as designated by the 
investigator. The investigator should also have the patient re-consent, explaining that re-introduction of study drug could lead to 
increased risk of recurrence.

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Table 8:
Recommendations for Hyperphosphatemia Management
Serum Phosphorus 
Resulta
(mg/dL and mmol/L)b
Gradec
Futibatinib Dose Interruption and Modificationd, e, f
Recommended Phosphate Binder for Management of 
Hyperphosphatemiag
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]. 
Re-assess serum phosphate within 7 days.
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. 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 titration,h if phosphate 
level continues to increase. 
7.0 < P ≤10.0 (mg/dL) 
2.26< P ≤3.23 (mmol/L)
Grade 3 
Dose reduce futibatinib to the next lower dose level and intensify 
phosphate lowering therapy.
Re-assess serum phosphate within 7 days and at least once a week. 
If the serum phosphorus level has resolved to ≤ Grade 2 within 14 days 
after dose reduction, continue futibatinib at the reduced dose level. 
If the serum phosphorus level has not resolved to ≤Grade 2 after 14 days, 
further reduce futibatinib 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 futibatinib (or no lower than 12 mg QD), 
interrupt dosing with futibatinib until it is resolved to ≤Grade 2 before 
resuming futibatinib at the reduced dose prior to dose interruption.
P >10.0 (mg/dL) 
P >3.23 (mmol/L) 
Grade 4 
Interrupt futibatinib until it’s resolved to ≤ Grade 2, then resume 
futibatinib at the next lower dose level and intensify phosphate lowering 
therapy.
Re-assess serum phosphate within 7 days and at least once a week. If after 
2 dose interruptions and 2 dose reductions the serum phosphorus level has 
not resolved to ≤ Grade 2 after 14 days, permanently discontinue 
futibatinib.
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 x 0.3229 (conversion factor)
c This grading for the range of serum phosphorus levels will be used for the protocol.
d Interrupt futibatinib if any toxicities are intolerable, regardless of the grade (including Grade 1 and 2). If or when the toxicity 
resolves to a tolerable state, consideration can be given to resuming futibatinib at the same dose if deemed appropriate or 
reduced by one dose level if needed.
e Serum calcium levels should be assessed at the same time.
f Futibatinib will be permanently discontinued if ectopic mineralization or calcification associated with hyperphosphatemia and
considered clinically significant are observed
g 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
h Titrate the dose every 2-3 weeks until an acceptable serum phosphate level is reached.

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5.2.2.
Dose Modifications for Hematologic Toxicities
Criteria for dose interruption and resumption for hematologic toxicities for patients in Cohorts A 
and B are presented in Table 9. For patients in Cohort C, dose modifications will be made at the 
Investigator’s discretion.
Table 9:
Futibatinib Dose Interruption and Modification Criteria for Related Hematologic 
Toxicities for Patients in Cohorts A and B
CTCAE Grade (value) 
Recommended dose modification any time during a cycle of 
futibatiniba
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 with 
a single temperature of ≥ 38.3°C [101° F] 
or a sustained temperature of  ≥38° C 
[100.4° F]) 
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.
a  Interrupt futibatinib if any toxicities are intolerable, regardless of the grade (including Grade 1 and 2). If or when 
the toxicity resolves to a tolerable state, consideration can be given to resuming futibatinib at the same dose if 
deemed appropriate or reduced by one dose level if needed.

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5.2.3.
Dose Modifications in Case of Induced Drug Liver Injury (Hy’s Law)
Futibatinib will be permanently discontinued if liver function test abnormalities fulfill Hy’s Law 
criteria defined as:
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; liver metastases; or another 
drug capable of causing the observed liver injury):

Elevated aminotransferase enzymes of >3 x ULN

Alkaline phosphatase (ALP) <2 x ULN

Associated with an increase in bilirubin ≥2 x ULN
5.3.
Treatment Compliance
Each patient will be instructed to comply with the dosing regimen of futibatinib.
Compliance to all study medication administration should be documented in the patient’s source 
documents (Section 5.6.3).
5.4.
Concomitant Medications and Therapies
5.4.1.
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 Medical Monitor, it can be administered, but the patient will be censored for the 
primary endpoint analysis.
5.4.2.
Concomitant Medications and Therapies Requiring Precautions 
Supportive treatment is allowed based on available institutional or local guidelines.
Local or regional palliative cryotherapy or radiation, such as for bone pain or palliative surgery 
(non-anti-neoplastic intent), are permitted (provided the target lesion is not a site of measurable 
disease and is not indicative of disease progression).  Study therapy should be ceased a minimum 
of 2 days prior to administration of palliative treatment, and may be resumed 7 days after the 
procedure or when the patient has recovered from the side effects of the procedure.
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 American Society of Clinical Oncology (ASCO) guidelines 
(Smith et al. 2015). 

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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).
5.4.3.
Drug Interactions
The following information is based on results from in vitro studies and preliminary results from 
clinical pharmacology studies of drug interactions studies. Caution is advised if these drugs are 
given concomitantly (see Appendix C, 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 
futibatinib. The preliminary clinical pharmacology results suggested that strong CYP3A inhibitor 
increase futibatinib exposure and that a strong CYP3A inducer decrease the exposure. CYP3A 
inhibitors and inducers may alter the concentration and activity of futibatinib.
CYP3A substrates: Futibatinib is a potential time-dependent inhibitor of CYP3A. However, 
preliminary clinical pharmacology result suggested that futibatinib had no significant effect on 
exposure of sensitive CYP3A substrate.
P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) inhibitors: Futibatinib is a 
potential inhibitor of P-gp and BCRP. Futibatinib may alter the PK and activity of P-gp and 
BCRP substrates. 
P-gp and BCRP substrates: Futibatinib is a substrate of P-gp and BCRP. P-gp and BCRP 
inhibitors may alter the concentration and activity of futibatinib.
5.5.
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 study medication, 
or longer if necessary based on local requirements. Effective contraception is defined as follows:

Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation:

Oral

Intravaginal

Transdermal

Progestogen-only hormonal contraception associated with inhibition of ovulation:

Oral

Injectable

Implantable

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
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 
method) 
Male patients, unless sterile (vasectomy with post-procedure semen analysis), with partners who 
are WOCBP should use a male condom in combination with at least one of the effective 
contraception methods during the study and for 90 days or longer based on local requirements
after the last dose of study medication. Donation of sperm or ova is not allowed during the study 
and for 90 days or longer based on local requirements following the last dose of study drug.
5.6.
Study Drug Materials and Management
Futibatinib will be supplied by the Sponsor. Detailed information such as the requirements for 
accountability and disposal of study drug can be found in the Pharmacy Manual, which will be 
provided separately.
5.6.1.
Description of Study Drug
Futibatinib will be provided as 4-mg tablets for oral use. Please refer to the Investigator’s 
Brochure for additional information.
5.6.2.
Packaging and Labeling
Futibatinib will be packaged and labelled according to local laws and regulations.
5.6.3.
Storage
Futibatinib tablets should be stored in accordance with the label.
5.6.4.
Accountability
The Investigator is responsible for ensuring that all study drug received at the site is inventoried 
and accounted for throughout the study. All study drugs will be stored and disposed of according 
to the Sponsor's instructions. The dispensing of study drug to the patient and the return of study 
drug from the patient must be documented in the patient’s source documents. Patients must be 
instructed to return all original containers, whether empty or containing study drug. 
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.

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6.
STUDY ASSESSMENTS
The Schedule of Events (Table 1 for Cohorts A and B, Table 2 for Cohort C, and Table 3 for 
Extension Phase) 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.
Any AEs directly associated with a screening procedure should be reported as described in 
Section 9.2.
Assessment
Details
Review of inclusion/exclusion 
criteria
See Section 4.1 and 4.2.
Eligibility must be confirmed prior to first dose of study therapy.
Demographics/medial history
Sex, age, clinical diagnosis, date and method of diagnosis, prior cancer therapy, 
relevant medical history (past and concurrent).
Baseline signs and symptoms
Signs and symptoms occurred after signing of ICF but before administration of 
first dose of futibatinib.
Physical examination
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.
12-lead electrocardiogram
Single, resting, semirecumbent 12-lead electrocardiogram 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 electrocardiogram data.
Hematology
Red blood cell count, hemoglobin, hematocrit, platelets, white blood cell count 
with differential, neutrophils (ANC), lymphocytes, monocytes, eosinophils, 
basophils
Serum chemistry
AST, ALT, alkaline phosphatase, total bilirubin, direct bilirubin, albumin, lactate 
dehydrogenase, inorganic phosphorus, triglyceride, total cholesterol, creatinine, 
urea or blood urea nitrogen, bicarbonate, sodium, potassium, chloride, calcium 
(corrected value), magnesium, blood glucose, uric acid 
For a calculated creatinine clearance (CrCl) value, use the Cockcroft-Gault 
formula:
Male CrCl (mL/min) = Body wt (kg)×(140-age)[72×serum creatinine (mg/dL)]
Female CrCl (mL/min) = male CrCl×0.85
Coagulation
Prothrombin time-international normalized ratio, activated partial thromboplastin 
time, fibrinogen
Pregnancy test
Serum β human chorionic gonadotrophin (human chorionic stimulating 
hormone) test required for WOCBP
Ophthalmological examination
See Section 6.1
PK blood sampling
See Section 7.

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Assessment
Details
Pharmacodynamic biomarker
blood sampling
See Section 10
Efficacy assessments
See Section 8.
Concomitant 
medication/concomitant therapy
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.
AE monitoring
All AEs will be collected from the time the ICF is signed through 30 days after 
the last dose of any study therapy (safety follow-up) or until the start of new 
antitumor therapy, whichever is earlier.  See Section 9.
Abbreviations: AE=adverse event; ALT=alanine aminotransferase; ANC=absolute neutrophil count; AST=aspartate 
aminotransferase; CrCl=calculated creatinine clearance; ICF=informed consent form; QT = QT interval; QTcF = Fridericia's 
Correction Formula; RR=intra-beat; WOCBP=women of childbearing potential
6.1.
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 by an ophthalmologist or qualified delegate at 
screening and 4-6 weeks after first dose; additional on-study evaluation as needed due to 
physician judgment and/or symptoms or signs of mineral deposits.  
Each evaluation will encompass: 

External ocular examination

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)

Dilation of the pupil with direct/indirect fundoscopy per institutional guidelines and 
local clinical practice
6.2.
Laboratory Assessments
All laboratory assessments will be performed locally. The laboratory must provide normal 
reference ranges for hematology, chemistry, and coagulation tests. If justified (eg, deterioration 
of the patient’s health conditions and/or distance from the clinical site) and allowed by the 
country and institution, laboratory tests performed by external laboratories may be used for the 
study. However, laboratory reference ranges and accreditation are required. All laboratory test 
results (internal or external) must be reviewed for clinical significance by the Investigator. 
Any clinically significant events must be followed and reported as required by the protocol 
(please see Section 9.3.1).

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7.
PHARMACOKINETICS
The PK population will consist of all patients who received futibatinib and have evaluable blood 
samples for analysis. Blood samples will be obtained from all patients at the timepoints listed in 
Table 10 and used to determine plasma futibatinib concentrations. 
In the event that a patient interrupts treatment after the pre-dose sample is collected and restarts 
the treatment at a later date, a pre-dose sample should be collected.
Table 10:
Pharmacokinetic Blood Sample Collection
Day of Study
(Time Window)
Collection Time Point (hours) in Relation to Futibatinib Administration 
(Time Window)
Day 15 of Cycle 1
(± 3 days)
Pre-dose (from -30 min to just before dose)
1 hour±30 min post-dose
3 hours±30 min post-dose

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8.
EFFICACY EVALUATIONS
8.1.
Cohorts A and B
8.1.1.
Efficacy Criteria
For patients in Cohorts A and B, 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). Primary objective and additional 
secondary objectives will be assessed by an IRC.
Results of the local 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 decisions. 
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. 
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.
8.1.2.
Method of Imaging
The same method of assessment and 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.

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8.1.3.
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.
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:

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
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.” 
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 electronic case report form (eCRF) (eg, multiple enlarged pelvic 
lymph nodes or multiple liver metastases).
8.1.4.
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).
8.1.4.1.
Target and Non-Target Response Assessments
Assessments will be based on the definitions for target and non-target lesions described in
Table 11.

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Table 11:
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.
8.1.4.2.
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 is noted. 

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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.
8.1.5.
Objective Response Assessment
Assessments will be based on the definitions provided in Table 12 and Table 13. Since this is a 
non-randomized study, all responses (CR/PR) must be confirmed.
Table 12:
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 13:
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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8.2.
Cohort C
8.2.1.
Efficacy Criteria
Efficacy will be assessed by evaluation of:

bone marrow histomorphology changes, standard cytogenetics, and FGFR molecular 
status

peripheral blood assessment (blood count) including potentially FGFR molecular status

PET scan for fluorodeoxyglucose (FDG) avid lesions

imaging (CT/MRI) in case of presence of solid lesions

clinical assessment
If the Investigator determines that a patient has developed clinical disease progression 
manifested by symptomatic deterioration, the patient may stop treatment. Every effort should be 
made to document objective disease progression even after discontinuation of treatment.
8.2.2.
Response Criteria 
For patients in Cohort C, response will be determined based on disease presentation. 
Investigators will assess response based on the following response criteria:

Treatment Response Criteria for MDS/MPN (Savona et al. 2015)

Response Evaluation Criteria in Lymphoma (RECIL 2017) (Younes et al. 2017)

International Working Group (IWG) Response Criteria for AML (Cheson et al. 2003)
A review of the response assessments will be conducted by an adjudication committee.
8.2.3.
Response Definitions
Response will be determined based on investigators’ assessment of imaging, bone marrow, 
peripheral blood, and extramedullary disease. Assessments will be based on the definitions 
described in Table 14.

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Table 14:
Response Definitions for Cohort C
MLN Characteristic
MLN Only
Lymphoma Presentation
Leukemia Presentation
Response Criteria
Savona 2015a
RECIL 2017b
Cheson 2003c
Complete response (CR)
Must fulfill all criteria defined for 
CR 
Must fulfill all criteria defined 
for CR 

Must fulfill all criteria defined for 
morphologic complete response

CR does not include:
o
morphologic leukemia-free state
o
complete response with incomplete 
hematological recovery (CRi), or 
o
cytologic complete response (CRc)
Partial response (PR)
Must fulfill all criteria defined for 
PR
Must fulfill all criteria defined 
for PR
Must fulfill all criteria defined for partial remission  
Complete response with 
incomplete blood count 
recovery (CRi)
N/A
N/A
Must fulfill all criteria defined for CRi
Complete cytogenetic 
response (CCyR)
Resolution of previously present 
chromosomal abnormality known 
to be associated with MLN (eg. 
8p11 translocation)
Must fulfill all criteria defined 
for CCyR (Savona 2015)a
Must fulfill all criteria defined for cytogenetic 
complete response (CRc) (Cheson 2003)c and 
CCyR (Savona 2015)a
Partial cytogenetic 
response (PCyR)
≥50% reduction of chromosomal 
abnormality known to be 
associated with MLN (eg. 8p11 
translocation)
Must fulfill all criteria defined 
for PCyR (Savona 2015)a
Must fulfill all criteria defined for PCyR 
(Savona 2015)a
PD/Relapsed disease
Must fulfill all criteria defined for 
PD/relapsed disease 
Must fulfill all criteria defined 
for PD/relapsed disease 
Must fulfill all criteria defined for PD/relapsed 
disease 
a Savona, et al. An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults. 
Blood. 2015.
b Younes, et al. International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017). Ann Oncol. 2017.
c Cheson, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and 
Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003.

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9.
SAFETY EVALUATIONS
9.1.
Adverse Events
An AE is defined as 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. For this study, progression of the cancer under study is not considered an adverse 
event.
All AEs will be collected from the time the ICF is signed through 30 days after the last dose of 
any study therapy (safety follow-up) or until the start of new antitumor therapy, whichever is 
earlier. For all AEs that occur between signing ICF, there is no need to record those that are 
unrelated unless it is mandatory by local regulations. 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.
Signs and symptoms of a pre existing disease should not be considered an AE, but should rather 
be considered baseline signs and symptoms. Clinically significant worsening of pre existing 
signs and symptoms is considered an AE.
9.2.
Reporting of Adverse Events
9.2.1.
Terms of Reported Adverse Events
All AEs will be documented in the eCRF according to the eCRF Completion Guidelines. 
Documentation should include onset and resolution/stabilization dates, severity/grade, 
relationship to study drug, and outcome of the event. 
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 one or more AEs.
9.2.2.
Severity of Adverse Events
The NCI-CTCAE V5.0 will be used to grade the severity of AEs.
9.2.3.
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.

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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 at least 
one of the following conditions is true:

The event occurred prior to study drug administration.

There is no reasonable possibility that the study drug caused the event. (“no 
reasonable possibility” means there is no evidence to suggest a causal relationship 
between the study drug and the AE)

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. 
9.2.4.
Outcome of Adverse Events
Record the outcome of AEs as follows:

Resolved

Not resolved

Fatal
9.2.5.
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

Withdrawal of consent

Death

Other (eg, transfer to another hospital)

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9.3.
Laboratory Assessments
9.3.1.
Reporting and Evaluation of Laboratory Test Results
All laboratory results must be reviewed by the Investigator. A new laboratory 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 futibatinib. 
The NCI-CTCAE V5.0 will be used to grade the severity of laboratory data.
9.3.2.
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.
9.4.
Serious Adverse Events
9.4.1.
Definitions of Serious Adverse Events
An SAE is any untoward medical occurrence that at any dose: 

Results in death

Death due to disease progression or relapse is not considered an SAE unless the 
investigator deems it possibly related to the study drug

Is life-threatening

The term "life-threatening" 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. 

The following are not considered hospitalizations for the purposes of assessing 
seriousness (however, one of the other serious criteria may apply):

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).

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
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). 
9.4.2.
Reporting of Serious Adverse Events (within 24 hours)
All SAEs occurring from the time the ICF is signed through the Safety Follow-up Period 
(30 days after the last dose of study treatment or discontinuation of the Safety Follow-up Period, 
whichever is earlier) must be reported to 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 serious criterion. The SAE reporting process and contact 
information are provided in supplement guidelines.
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 SAE form.
The Investigator also must submit further information if it is required by the Sponsor or the 
director of the study site or an institutional review board (IRB)/independent ethics committee 
(IEC).
Every SAE should be followed until it has resolved, stabilized, or returned to baseline.
9.4.3.
Reporting of Deaths (within 24 hours)
All deaths (except disease progression) occurring from the time the ICF is signed through the 
Safety Follow-up Period (30 days after the last dose of study treatment or discontinuation, 
whichever is earlier) must be reported within 24 hours from the time the Investigator first 
becomes aware of the death. The primary cause of the death should be reported as the SAE term, 
if available, and entered on the death page of the eCRF.
9.5.
Other Safety Information
9.5.1.
Pregnancy
If a patient becomes pregnant while in the study, the study treatment must be immediately 
discontinued. Pregnancy information in a female patient (or for the female partner of a male 
patient) should be reported to Sponsor’s Pharmacovigilance or designee via th Pregnancy Form 
as soon as possible from the time the Investigator first becomes aware of a pregnancy or its 
outcome.
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 or designee. Pregnancies must be followed to outcome by the Investigator, 
even after study completion. 

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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 an SAE to the Sponsor’s Pharmacovigilance or 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.
9.5.2.
Overdose
An overdose is the accidental or intentional use of a drug in an amount higher than the dose 
being studied. An overdose or incorrect administration of study treatment is not itself an AE, but 
it may result in an AE. 
An overdose that results in an AE should be reported to Sponsor’s Pharmacovigilance or 
designee within 24 hours from the time the Investigator first becomes aware of its occurrence.

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10.
BIOMARKER EVALUATION
10.1.
Biomarker Assessments
10.1.1.
Objectives and Background
Exploratory objectives of this study are to assess the possible impact of specific genetic 
alterations or other laboratory abnormalities on the efficacy of futibatinib.
Biomarkers will be tested using analytically validated assay at a central laboratory.
All biomarker assessments described in this section will be performed at the timepoints shown in 
the Schedule of Events; methods of sample collection and preparation will be described in a 
separate Laboratory Manual.
10.1.2.
Assessment of FGF/FGFR Aberrations in Blood
A blood sample will be collected to assess FGF/FGFR aberrations in ctDNA as described in the 
Schedule of Events and where local regulations allow. In addition to assessing ctDNA as a 
pharmacodynamic biomarker, samples or a set of samples, will be used to investigate its possible 
utility as a complimentary or an alternative to tumor tissues for the future potential companion 
diagnostic development. Samples will be collected and stored, as per the Laboratory Manual, and 
analyzed in batches.
10.1.3.
Tissue Samples
Archival or fresh tumor/bone marrow biopsy samples will be collected during screening to 
retrospectively confirm FGFR gene status at the Sponsor’s designated central laboratories or for 
the purpose of a bridging study should companion diagnostics be warranted (fine needle
aspiration is not acceptable). Formalin-fixed, paraffin embedded (FFPE) tissue blocks are 
preferred to slides.  The remaining samples may be stored at the Sponsor’s designated central 
laboratories for up to 10 years after study completion for future testing or companion diagnostic
development if warranted.
10.2.
Sample Storage and Disposal
Samples or leftover samples will be stored for a maximum of 10 years following the completion 
of the study at central laboratories. These samples could be used to develop companion 
diagnostics and to investigate the genes or other biomarkers related to efficacy or resistance of 
futibatinib in the future. After the storage period ends, samples will be destroyed.
10.3.
Analytical Procedures
Patients will be enrolled depending on local results but tissue samples will be collected and 
stored at central location for possible confirmatory testing, molecular profiling and/or companion 
diagnostic development if warranted by the clinical response.
Analyzing plasma ctDNA will be conducted retrospectively in batches on an adequately 
validated assays at central lab(s). 
The detailed analytical procedures will be described in the SAP for Biomarkers.

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11.
STATISTICAL CONSIDERATIONS
The statistical analysis methods will be documented in detail in the SAP.
11.1.
Estimation of Sample Size
A total of approximately 115 patients will be enrolled in the study. 
Approximately 60 patients with solid tumors harboring FGFR rearrangements will be enrolled in 
Cohort A. Sample size considerations (primary endpoint ORR) are based on a 2-stage Simon 
design (Simon 1989), comparing a poor response of ≤10% vs a promising response of ≥25%, at 
a 5% 1-sided significance level and approximate 90% power.

In Stage 1 (futility assessment), enrollment will include 35 patients and accrual will 
continue to Stage 2, if at least 4 (11.4%) of 35 patients respond (CR or PR).

In Stage 2, if the Stage 1 futility boundary is exceeded, an additional 25 patients will be
enrolled, for a total of approximately 60 patients. With a total of 60 patients, if the 
observed ORR is 30%, the 95% exact confidence interval (CI) is (18.9%, 43.2%).
Table 16:
Observed ORR with Exact 95% Confidence Interval (Cohort A)
ORR
95% Exact Confidence Interval
20%
[10.8% - 32.3%]
25%
[14.7% - 37.9%]
30%
[18.9% - 43.2%]
Approximately 35 patients with gastric or GEJ cancer harboring FGFR2 amplification will be 
enrolled in Cohort B.  Sample size considerations are based on differentiating a historical control 
ORR of 10% or less, with a target ORR of 35%. Assuming the true ORR is 35%, the cohort has 
approximately 96% power to reject the null hypothesis that the true ORR is ≤10%, considering a 
2-sided alpha of 5%. With a sample size of 35, observing at least 8 responders will have a 95% 
CI lower bound excluding 10% (ORR of 23% with 95% CI (10.4% - 40.1%). 
Table 17:
Observed ORR with Exact 95% Confidence Interval (Cohort B)
ORR
95% Exact Confidence Interval
23%
[10.4% - 40.1%]
29%
[14.6% - 46.3%]
37%
[21.5% - 55.1%]
Approximately 20 patients with myeloid or lymphoid neoplasms harboring FGFR1
rearrangements will be enrolled in Cohort C. Sample size considerations are based on 
differentiating a historical control CR rate of 10% or less with a target CR rate of 50%. 

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Assuming the true CR rate is 50%, the cohort has over 95% power to reject the null hypothesis 
that the true CR rate is ≤10%, considering a 2-sided alpha of 5%.
Observing at least 6 responders out of 20 treated patients will have a 95% CI lower bound 
excluding 10% (CR rate of 30% with 95% CI (11.9% - 54.3%). 
Table 18:
Observed CR Rate with Exact 95% Confidence Interval (Cohort C)
CR Rate
95% Exact Confidence Interval
30%
[11.9% - 54.3%]
40%
[19.1% - 64.0%]
50%
[27.2% - 72.8%]
11.2.
Planned Interim Analysis
The Sponsor will review the data at the time Cohort A has the required number of patients to 
determine if that particular cohort should continue. 
11.3.
Analysis Populations
The analysis populations in the study are defined in Table 19.
Table 19
Definitions of Analysis Populations
Analysis Population
Definition
All Enrolled Population:
All patients who signed the ICF in this study
All Treated Population/Full Analysis Set:
All enrolled patients who received at least 1 dose of 
study drug
Pharmacodynamic/Biomarker Evaluable Set:
All patients in the All Treated Population who have 
evaluable pharmacodynamic/biomarker data for 
analyses
11.4.
Criteria for Handling of Patient Data
The criteria for handling of patient data are provided in the SAP.
11.5.
Statistical Analyses
11.5.1.
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.

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11.5.2.
Study Drug Administration
In the All Treated Population, the following analyses will be performed by dose level:

Administration status

The total dose, total duration of administration and the number of administration 
cycles will be summarized by all treated patients/each intervention group.

Status of administration completion

The rate of administration completion will be presented by cycle.

The presence or absence of study discontinuation and reasons for study 
discontinuation will be tabulated by cycle.

Dose intensity

Actual dose intensity and relative dose intensity in each patient will be calculated, and 
descriptive statistics will be presented.
11.5.3.
Efficacy Analyses 
All efficacy analysis will be performed using the All Treated Population
A description of each efficacy endpoint is provided in Table 15. See the SAP for more detailed 
information on the efficacy analyses.
11.5.3.1.
Cohorts A and B
11.5.3.1.1. Primary Efficacy Analysis
Objective response rate is defined as the proportion of patients with objective evidence of CR or 
PR. The evaluation of ORR will be based on an independent central review of radiologic images. 
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.
11.5.3.1.2. Secondary Efficacy Analyses
Overall response rate based on investigator assessment will be determined as decribed above for 
the primary analysis of ORR based on independent central review of radiologic images 
(Section 11.5.3.1.1 ).
Disease control rate will be analyzed using the same methodology as ORR 
Duration of response will only be evaluated in patients with an 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.  

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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 in a similar manner to PFS. In the absence of confirmation of 
death or for patients who are alive as of the OS cut-off date, survival time will be censored at the 
last known date that the patient was alive.
11.5.3.2.
Cohort C
11.5.3.2.1. Primary Analysis
Complete response rate defined as the proportion of patients who achieved a CR will be 
calculated and the exact 2-sided CI will also be derived using the Clopper Pearson methodology.
11.5.3.2.2. Secondary Analyses
The overall response, CR+CRi (leukemia presentation only), CCyR, and PCyR rates will be 
calculated and the exact 2-sided CIs will also be derived using the Clopper-Pearson 
methodology.
Duration of CR (only in patients who achieved a CR), duration of CR+CRi (only in patients who 
achieved a CR/CRi [leukemia presentation only]), and duration of response (only in patients with 
an objective response of CR, CRi [leukemia presentation only], or PR) will be estimated using 
the Kaplan-Meier method. 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.
Relapse-free survival will only be evaluated in patients with an objective response of CR and 
measured from the first date of achieving CR until the first date of relapsed disease or death from 
any cause, whichever occurs first. Patients who die without a reported disease relapse will be 
considered to have relapsed on the date of their death. Patients who did not relapse or die will be 
censored on the date of their last tumor assessment. Patients who started any subsequent anti-
cancer therapy without a prior reported relapse will be censored at the last tumor assessment 
prior to initiation of the subsequent anti-cancer therapy.

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Event-free survival will be estimated only for patients with leukemia presentation using the 
Kaplan-Meier method. EFS is defined as the time from first dose of study therapy to treatment 
failure, relapse after CR (if applicable), or death from any cause, whichever occurs first. For a 
patient with none of these events before the end of study follow-up, observation of EFS is 
censored at the date of last contact prior to the analysis cut-off date. If the patient does not 
achieve a CR, EFS is defined as the point of treatment failure or death, whichever comes first. 
Treatment failure for EFS is defined as PD in this study.
Overall survival will be analyzed in a similar manner to PFS. In the absence of confirmation of 
death or for patients who are alive as of the OS cut-off date, survival time will be censored at the 
last known date that the patient was alive.
11.5.4.
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 V5.0, 
where applicable. 
Concomitant medications will be coded according to the WHO 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 futibatinib. 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 V5.0 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 electrocardiogram findings will be presented by patient.
11.5.5.
Pharmacokinetic Analysis
The concentration vs time data obtained in this study will be combined with data from other 
studies in the clinical development program to develop a Pop PK model. This model will be used 
to evaluate the effects of intrinsic and extrinsic covariates on the PK of futibatinib and to 
estimate measures of individual exposure (such as steady-state peak, trough and area under the 
plasma drug concentration-time curve). Model estimated exposures will be used for exposure-
response analyses of selected efficacy and safety endpoints. The results of Pop PK and exposure 
response analyses will be reported separately.

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11.5.6.
Pharmacodynamic/Biomarker Analysis
The exploratory pharmacodynamic/biomarker endpoints are described in Section 10.
Pharmacodynamic and biomarker data will be summarized descriptively using all patients in the 
Pharmacodynamic/Biomarker Evaluable Set who have evaluable data available.

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12.
ADMINISTRATIVE CONSIDERATIONS
12.1.
Protocol Compliance
The Investigator must agree to comply with all aspects of the protocol.  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. The new Investigator must accept the 
responsibility in writing and be approved by the Sponsor and the IRB/IEC.
12.2.
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.
12.3.
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.
12.4.
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.
12.5.
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, all relevant personnel will receive electronic data capture access according to their 
roles in the study.
An eCRF should be completed for each screened and enrolled patient.
The Investigator, or assigned personnel, should verify the data and correct as necessary prior to 
approval of the eCRFs.
12.6.
Access to Source Data/Documents
The Investigator and the site must make all study-related records available for study-related 
monitoring, audit, IRB/IEC review, and regulatory inspection.

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12.6.1.
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.
12.6.2.
Access to Source Data
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 
Investigator.
12.7.
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.
12.8.
Responsibilities of Recordkeeping
12.8.1.
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 of 
Technical Requirements for Pharmaceuticals for Human Use (ICH) E6 Guidelines. In 
multinational trials, non-United States sites will be considered non-Investigational New Drug 
(IND) sites. Non-IND sites will be required to follow local regulations and ICH Guidelines.
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.

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12.8.2.
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.
12.9.
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 and the site 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.
12.10.
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.
12.11.
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.
12.12.
Study Administrative Structure 
The study organization details will be maintained in a supplement.

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13.
QUALITY CONTROL AND QUALITY ASSURANCE
The Sponsor will perform quality control and quality assurance procedures in accordance with 
the Sponsor's standard operating procedures (SOPs) to ensure the quality of the clinical study.
13.1.
Quality Control
The Sponsor is responsible for controlling the quality of the clinical study according to the SOPs 
regarding study operation, monitoring, data collection and management, statistical analysis, and 
handling of safety information to verify that the study-related activities have been fulfilled.
13.2.
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 and the site 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 and the site 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 
and the site 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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14.
ETHICS
14.1.
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.
14.2.
Written Informed Consent
The ICF(s) must be approved by the IRB/IEC before patient’s sign consent for any study-related 
activity. It must be in a language that the patient can read and understand. The ICF process 
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) during their participation in the study (including during
survival follow-up).
14.3.
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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15.
PUBLICATION POLICY
15.1.
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.
The Investigator(s) 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.
15.2.
Secondary Use of Data
The Sponsor maintains the right to secondary use of data in this study.
Secondary use of data describes the use of data from this study for other study/studies for 
purposes including, but not limited to, drug development and/or academic research. Secondary 
use of data also includes external offerings of study data to domestic and/or foreign 
organization(s), other companies and researcher(s), on a case by case basis.

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16.
REFERENCES
Bain BJ, Gilliland DG, Horny HP, Vardiman JW, et al. Myeloid and lymphoid neoplasms with 
eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1. Haematologica. 2010; 
95:696-698.
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.
Buas MF, Vaughan TL. Epidemiology and risk factors for gastroesophageal junction tumors: 
understanding the rising incidence of this disease. Semin Radiat Oncol. 2013;23:3-9. 
Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, et al. Revised 
recommendations of the International Working Group for Diagnosis, Standardization of 
Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in 
Acute Myeloid Leukemia.  J Clin Oncol. 2003; 21(24):4642-4649.
Courjal F, Cuny M, Simony-Lafontaine J, Louason G, Speiser P, Zeillinger R, et al. Mapping of 
DNA amplifications at 15 chromosomal localizations in 1875 breast tumors: definition of 
phenotypic groups. Cancer Res. 1997;57(19):4360–4367. 
Deng N, Goh LK, Wang H,  Das K, Tao J, Tan IB,  et al. A comprehensive survey of genomic 
alterations in gastric cancer reveals systematic patterns of molecular exclusivity and 
cooccurrence among distinct therapeutic targets. Gut. 2012; 61:673–684.
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.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of 
cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–2917. 
Gallo LH, Nelson KN, Meyer AN, Donoghue DJ. Functions of fibroblast growth factor receptors 
in cancer defined by novel translocations and mutations. Cytokine Growth Factor Rev. 2015; 
26:425–449. 
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(1):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.
Jackson CC, Medeiros LJ, Miranda RN. 8p11 myeloproliferative syndrome: a review. Hum 
Pathol. 2010;41:461-476.
Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality 
rates and trends. Cancer Epidemiol Biomarkers Prev. 2010;19:1893–907. 
Jung EJ, Jung EJ, Min SY, Kim MA, Kim WH. Fibroblast growth factor receptor 2 gene 
amplification status and its clinicopathologic significance in gastric carcinoma. Hum Pathol.
2012;43:1559–1566. 

Futibatinib (TAS-120)
Protocol -TAS-120-202
Confidential - Proprietary Information
80
Kunii K, Davis L, Gorenstein J,  Hatch H, Yashiro M, Di Bacco A,  et al. FGFR2- amplified 
gastric cancer cell lines require FGFR2 and Erbb3 signaling for growth and survival. Cancer 
Res. 2008;68:2340–2348.
Lacombe D, Burock S, Bogaerts J, Schoeffski P, Golfinopoulos V, Stupp R. The dream and 
reality of histology agnostic cancer clinical trials. Mol Oncol. 2014; 8(6):1057–1063.
Liu YJ, Shen D, Yin X, Gavine P, Zhang T, Su X, et al. HER2, MET and FGFR2 oncogenic 
driver alterations define distinct molecular segments for targeted therapies in gastric carcinoma. 
Br J Cancer. 2014;110:1169–1178. 
Loriot Y, Necchi A, Hoon Park S, Garcia-Donas J, Huddart R, Burgess E, et al. Erdafitinib in 
locally advanced or metastatic urothelial carcinoma. N Engl J Med. 2019; 381:338-348.
Macdonald D, Aguiar RC, Mason PJ,  Goldman JM, Cross NC. A new myeloproliferative 
disorder associated with chromosomal translocations involving 8p11: a review. Leukemia.
1995;9:1628-1630. 
Macdonald D, Reiter A, Cross NC. The 8p11 myeloproliferative syndrome: a distinct clinical 
entity caused by constitutive activation of FGFR1. Acta Haematol. 2002;107(2):101-107.
Oken MM, Creech, RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity 
and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649-
655.
Savona MR, Malcovati L, Komroki R, Tiu RV, Mughal TI, Orazi A, et al. An international 
consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative 
neoplasms (MDS/MPN) in adults. Blood. 2015;125(12):1857-1865.
Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989;10:1-
10.
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, Grose R. Fibroblast growth factor signaling: from development to cancer. Nature Rev 
Cancer. 2010;10:116–129.
Villafuerte-Gutiérrez P, López Rubio M, Herrera P, Arranz E. A case of myeloproliferative 
neoplasm with BCR-FGFR1 rearrangement: favorable outcome after haploidentical allogeneic 
transplantation. Case Rep Hematol. 2018, Article ID 5724960, 4 pages. 
Williams SV, Hurst CD, Knowles MA. Oncogenic FGFR3 gene fusions in bladder cancer. Hum 
Mol Genet. 2013;22:795–803.
Wu YM, Su F, Kalyana-Sundaram S, Khazanov N, Ateeq B, Cao X, et al. Identification of 
targetable FGFR gene fusions in diverse cancers. Cancer Discov. 2013;3(6):636-647.
Yoshihara K, Wang Q, Torres-Garcia W, Zheng S, Vegesna R, Kim H, Verhaak RGW. The 
landscape and therapeutic relevance of cancer-associated transcript fusions. Oncogene. 2015; 
34:4845–54. 

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Younes A, Hilden P, Coiffier B, Hagenbeek A, Salles G, Wilson W, et al. International Working 
Group consensus response evaluation criteria in lymphoma (RECIL 2017).  Ann Oncol. 
2017;28(7):1436-1447.

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APPENDIX A. ECOG Performance
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. CLASSIFICATION OF SUBSTRATES, INHIBITORS, AND 
INDUCERS OF CYP ENZYMES AND TRANSPORTERS
The classification below is based on the FDA Draft Guidance for Industry, Clinical Drug Interaction Studies —
Study Design, Data Analysis, and Clinical Implications, October 2017. 
(http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM292362.pdf)
Example of CYP3A Inhibitors
Cytochrome P450 
(CYP) Enzymes
Strong Inhibitorsa
≥5-fold increase in AUC
Moderate inhibitorsb
≥ 2 but < 5-fold increase in AUC
CYP3A
boceprevir, clarithromycin, cobicistat, conivaptan, 
danoprevir and ritonavir, diltiazem, elvitegravir and 
ritonavir, grapefruit juice,c  indinavir and ritonavir, 
idelalisib, itraconazole, ketoconazole, lopinavir and 
ritonavir, 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
a
Strong inhibitors are drugs that increase  the area under the concentration-time curve (AUC) of sensitive index substrates of a 
given metabolic pathway ≥5-fold.
b
Moderate inhibitors are drugs that increase the AUC of sensitive index substrates of a given metabolic pathway ≥2 to 
<5-fold.
c
The effect of grapefruit juice varies widely among brands and is concentration-, dose-, and preparation dependent. 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).
Example of CYP3A Inducers
Cytochrome P450 
(CYP) Enzymes
Strong Inducers
≥ 80% decrease in AUC
Moderate Inducers
50-80% decrease in AUC
CYP3A
carbamazepine, enzalutamide, mitotane, 
phenytoin, rifampin, St. John’s worta
bosentan, efavirenz, etravirine, modafinil
a
The effect of St. John’s wort varies widely and is preparation-dependent.
Example of Inhibitors for P-gp and BCRP
Transporters
Gene
Inhibitor
P-gpa
ABCB1
Amiodarone, carvedilol, clarithromycin, dronedarone, 
itraconazole, lapatinib, lopinavir and ritonavir, propafenone, 
quinidine, ranolazine, ritonavir, saquinavir and ritonavir, 
telaprevir, tipranavir and ritonavir, verapamil
BCRPb
ABCG2
Curcumin, cyclosporine A, eltrombopag
a
P-gp: (1) AUC fold-increase of digoxin ≥2 with co-administration and (2) in vitro inhibitor.
b
BCRP: (1) AUC fold-increase of sulfasalazine ≥1.5 with co-administration and (2) in vitro inhibitor. Cyclosporine A and 
eltrombopag were also included, although the available DDI information was with rosuvastatin, where inhibition of both 
BCRP and OATPs may have contributed to the observed interaction.
Example of Substrates for P-gp and BCRP
Transporters
Gene
Substrate
P-gpa
ABCB1
Dabigatran, digoxin, fexofenadine
BCRPb
ABCG2
Rosuvastatin, sulfasalazine
a
P-gp: (1) AUC fold-increase ≥2 with verapamil or quinidine co-administration and (2) in vitro transport by P-gp expression 
systems, but not extensively metabolized.
b
BCRP: (1) AUC fold-increase ≥2 with pharmacogenetic alteration of ABCG2 (421C>A) and (2) in vitro transport by BCRP 
expression systems.

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