Conditions: Cholangiocarcinoma
Keywords: Cholangiocarcinoma fibroblast growth factor (FGF) fibroblast growth factor receptor (FGFR) FGF/FGFR alterations
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 147
Healthy volunteers: no

Brief summary:
The purpose of this study is evaluate the efficacy of pemigatinib in subjects with advanced/metastatic or surgically unresectable cholangiocarcinoma with FGFR2 translocation who have failed at least 1 previous treatment.

Detailed description:

Arms:
arm 1: Pemigatinib in subjects with FGFR2 translocation with a documented fusion partner in central laboratory report arm 2: Pemigatinibin subjects with other FGF/FGFR alterations arm 3: Pemigatinib in subjects negative for FGF/FGFR alteration

Interventions: intervention 1: Pemigatinib
Intervention descriptions: intervention 1: Pemigatinibonce a day by mouth for 2 consecutive weeks and 1 week off therapy

Protocol document:
Prot_000.pdf: 
Official Title: 
NCT Number: 
Document Date: 
A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the 
Efficacy and Safety of Pemigatinib in Subjects With Advanced/Metastatic 
or Surgically Unresectable  Cholangiocarcinoma Including FGFR2 
Translocations Who Failed Previous Therapy - (FIGHT-202)
NCT02924376
Clinical Study Protocol Amendment 7: 02 April 2020


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Clinical Study Protocol 
INCB 54828-202 
A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate 
the Efficacy and Safety of INCB054828 in Subjects With 
Advanced/Metastatic or Surgically Unresectable 
Cholangiocarcinoma Including FGFR2 Translocations Who Failed 
Previous Therapy 
Product: 
INCB054828 
IND Number: 
 
EudraCT Number: 
2016-002422-36 
Phase of Study: 
2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Original Protocol (Version 0): 
02 JUN 2016 
Amendment (Version) 1: 
14 SEP 2016 
Amendment (Version) 2: 
05 DEC 2016 
Amendment (Version) 3: 
18 JAN 2017 
Amendment (Version) 4: 
21 MAR 2017 
Amendment (Version) 5: 
03 OCT 2017 
Amendment (Version) 6: 
15 FEB 2018 
Amendment (Version) 7: 
02 APR 2020 
This study will be performed in accordance with ethical principles that have their origin in the Declaration of 
Helsinki and conducted in adherence to the study Protocol, Good Clinical Practices as defined in Title 21 of the 
US Code of Federal Regulations Parts 11, 50, 54, 56, and 312, as well as ICH GCP consolidated guidelines (E6) and 
applicable regulatory requirements. 
The information in this document is confidential.  No part of this information may be duplicated, referenced, or 
transmitted in any form or by any means (electronic, mechanical, photocopy, recording, or otherwise) without the prior 
written consent of Incyte Corporation. 


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INVESTIGATOR'S AGREEMENT 
I have read the INCB 54828-202 Protocol Amendment 7 (Version 7 dated 02 APR 2020) and 
agree to conduct the study as outlined.  I agree to maintain the confidentiality of all information 
received or developed in connection with this Protocol. 
(Printed Name of Investigator) 
(Signature of Investigator) 
(Date) 


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SYNOPSIS 
Name of Investigational Product:  INCB054828 
Title of Study:  A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and 
Safety of INCB054828 in Subjects With Advanced/Metastatic or Surgically Unresectable  
Cholangiocarcinoma Including FGFR2 Translocations Who Failed Previous Therapy 
Protocol Number:  INCB 54828-202 
Study Phase:  2 
Indication:  Advanced/metastatic or surgically unresectable cholangiocarcinoma 
Primary Objective: 
The primary objective of this study is to evaluate the efficacy of INCB054828 in subjects with 
advanced/metastatic or surgically unresectable cholangiocarcinoma with fibroblast growth factor receptor 
(FGFR) 2 translocation who have failed at least 1 previous treatment. 
Secondary Objectives: 
• To evaluate the efficacy of INCB054828 in subjects with advanced/metastatic or surgically unresectable
cholangiocarcinoma with different molecular subgroups.
• To evaluate the safety of INCB054828 in subjects with advanced/metastatic or surgically unresectable
cholangiocarcinoma.
• To identify and evaluate covariates that may influence the pharmacokinetics of INCB054828 in this
subject population through population pharmacokinetic analysis.  Additionally, exposure-response
analyses for key efficacy and safety parameters will also be considered if sufficient data are available.
Primary Endpoint: 
The primary endpoint of this study is to determine the objective response rate (ORR) in subjects with 
FGFR2 translocations based on the central genomics laboratory results.  Objective response rate is 
defined as the proportion of subjects who achieved a complete response (CR; disappearance of all target 
lesions) or a partial response (PR; ≥30% decrease in the sum of the longest diameters of target lesions) 
based on RECIST version 1.1.  Clinical response will be determined by an independent radiological 
review committee. 
Secondary Endpoints: 
• ORR in subjects with fibroblast growth factor (FGF)/FGFR alterations other than FGFR2 translocations
(Cohort B).
• ORR in all subjects with FGF/FGFR alterations (Cohorts A and B).
• ORR in subjects negative for FGF/FGFR alterations (Cohort C [US only]).
• Progression-free survival (PFS = first dose to progressive disease [PD] or death; all cohorts).
• Duration of response (DOR = time from the date of CR or PR until PD; all cohorts).
• Disease control rate (DCR = CR + PR + stable disease; all cohorts).
• Overall survival (OS = first dose to death of any cause; all cohorts).


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• Safety and tolerability will be assessed by evaluating the frequency, duration, and severity of adverse 
events; through review of findings of physical examinations, changes in vital signs, and 
electrocardiograms; and through clinical laboratory blood and urine sample evaluations (all cohorts). 
• Population pharmacokinetics (all cohorts). 
Overall Study Design:   
This is an open-label, monotherapy study of INCB054828 in subjects with advanced/metastatic or 
surgically unresectable cholangiocarcinoma with FGFR2 translocations, with other FGF/FGFR 
alterations, or who are negative for FGF/FGFR alterations.  The study will enroll approximately 
100 subjects into Cohort A (FGFR2 translocations), 20 subjects into Cohort B (other FGF/FGFR 
alterations), and 20 subjects into Cohort C (US only; negative for FGF/FGFR alterations).  Subjects will 
receive a once daily (QD) dose of INCB054828 at 13.5 mg on a 2-week-on therapy and 1-week-off 
therapy schedule. 
Subject eligibility can be based on local genomic testing results, if available.  Confirmatory testing 
through the central genomics laboratory will be performed on all subjects. 
Genomic testing results will allow subjects to be assigned to a cohort: 
• Cohort A:  FGFR2 translocations with a documented fusion partner in central laboratory report  
• Cohort B:  other FGF/FGFR alterations 
• Cohort C (US only):  negative for FGF/FGFR alterations 
Subjects enrolled based on a local sequencing report will be assigned to a cohort based on the local 
results.  However, final cohort assignment for statistical analysis of primary and secondary endpoints will 
be done based on the central genomics testing results. 
Treatment will start on Day 1.  Subjects will undergo regular safety assessments during treatment as well 
as regular efficacy assessments.  Subjects will be allowed to continue administration in 21-day cycles 
until documented disease progression or unacceptable toxicity is reported. 
Study Population:   
Subjects with advanced/metastatic or surgically unresectable cholangiocarcinoma with FGFR2 
translocations, with other FGF/FGFR alterations, or who are negative for any FGF/FGFR alterations, who 
failed at least 1 previous treatment. 
Key Inclusion Criteria:   
• Men and women, aged 18 or older. 
• Histologically or cytologically confirmed advanced/metastatic or surgically unresectable 
cholangiocarcinoma.  Subjects will be assigned to one of 3 cohorts: 
− Cohort A:  FGFR2 translocations with a documented fusion partner in central laboratory report 
− Cohort B:  other FGF/FGFR alterations 
− Cohort C (US only):  negative for FGF/FGFR alterations 
• Radiographically measurable disease per RECIST v1.1. 
• Documentation of FGF/FGFR gene alteration status. 


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• Documented disease progression after at least 1 line of prior systemic therapy. 
• ECOG performance status of 0 to 2. 
• Life expectancy ≥ 12 weeks. 
Key Exclusion Criteria:   
• Prior receipt of a selective FGFR inhibitor. 
• History of and/or current evidence of ectopic mineralization/calcification, including but not limited to 
soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes and asymptomatic 
arterial or cartilage/tendon calcifications. 
• Current evidence of clinically significant corneal or retinal disorder confirmed by ophthalmologic 
examination. 
• Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half-lives, whichever is shorter, 
before the first dose of study drug.  Topical ketoconazole will be allowed. 
INCB054828, Dosage, and Mode of Administration:   
INCB054828 will be self-administered as a QD oral treatment on a 2-weeks-on therapy and 1-week-off 
therapy schedule.  Each dose of INCB054828 should be taken immediately upon rising or after a 2-hour 
fast; subjects will fast for an additional 1 hour after taking study drug.  Tablets will be available in 
strengths of 2 mg and 4.5 mg.  The starting dose will be 13.5 mg.  One cycle will be defined as 21 days. 
Reference Therapy, Dosage, and Mode of Administration:   
Not applicable. 
Study Schedule/Procedures:   
Subjects will have regularly scheduled study visits at the clinical site as part of a 21-day cycle.  Study 
visits are as follows: 
• Prescreening:  To obtain FGF/FGFR status, if unknown (results within approximately 2 years of 
screening are valid for this study) 
• Screening:  Day -28 through Day -1 
• Cycle 1:  Days 1, 8, and 15 
• Cycles 2+:  Day 1 
• End of treatment 
• Safety follow-up:  30 days (+ 5 days) from date of last dose 
• Follow-up for disease status and survival:  Disease status follow-up every 9 weeks for subjects who 
discontinue for reasons other than disease progression.  Survival follow-up every 12 weeks after 
discontinuation.   
Local Laboratory Tests: 
Study visits will include sample collection for hematology, chemistry, coagulation, endocrine monitoring, 
lipids, and urinalysis testing.  Additionally, HIV screening (required for subjects outside of the US) and 
hepatitis screening (serology) will be done at screening;  pregnancy testing will be done at screening, 
Day 1 of every cycle before dose administration, and EOT.  FGF/FGFR status may be determined locally. 
Central Laboratory Assessments: 
Tumor tissue will be evaluated through the central laboratory for confirmation of FGF/FGFR alteration 
status. 
Blood samples for population pharmacokinetic analysis 
 
 will be collected at various timepoints throughout the study and analyzed at the central 
laboratory or designee. 


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Clinical Assessments: 
Adverse event assessments, vital signs, electrocardiograms, physical examinations, ECOG performance 
status, comprehensive eye examinations, and tumor and disease response assessments will be performed 
by the investigative site.   
An objective assessment of disease status will be performed at screening.  Subsequently, disease status 
including RECIST radiological response assessment will be assessed every 2 cycles for the first 4 cycles 
and every 3 cycles thereafter.  A central radiology group will be contracted to provide centralized reading 
on all assessments.   
Estimated Duration of Participation:   
Up to 28 days are allowed for screening, followed by continuous treatment in consecutive 21-day cycles 
as long as subject is receiving benefit and has not met any criteria for study withdrawal, and 30 days 
(+5 days) for safety follow-up following the last dose of the study drug.  Subjects will be followed-up for 
overall survival following documented disease progression. 
Estimated Number of Subjects:   
Approximately 140 subjects will be enrolled (approximately 100 subjects in Cohort A, and approximately 
20 subjects into Cohort B and Cohort C [US only] each). 
Principal Coordinating Investigator:  
, MD 
Statistical Methods:   
Primary analysis will be performed on FGFR2 translocated subjects.  Approximately 100 subjects with 
documentation of FGFR2 translocation from the central genomics laboratory are planned for the final 
analysis of the primary endpoint of ORR.  With the assumed rates of 33% for the intervention, a sample 
size of approximately 100 subjects would provide > 95% probability to have a 95% confidence interval 
with lower limit of > 15% assuming 10% lost to follow-up.  Up to 20 subjects will be enrolled in Cohorts 
B and C (US only), respectively, which will provide > 80% chance of observing at least 4 responders in 
each cohort if the underlying ORR is 30%. 
The proportion of subjects with ORR and DCR will be estimated with 95% CI.  The PFS, DOR, and OS 
will be analyzed by the Kaplan-Meier method.  Descriptive statistics will be summarized for safety data. 
Futility Analysis 
For Cohort A (FGFR2 translocations), futility analysis will be performed when approximately 25 subjects 
are enrolled into the cohort and have at least 1 tumor assessment or have permanently discontinued study 
treatment.  Cohort A can be stopped for futility if 2 or less responders are observed, for which there is less 
than 10% probability of claiming ORR > 15% based on a 60 subject cohort, as initially planned before 
Amendment 5.  This rule is just a guidance and nonbinding. 
Cohorts B (other FGF/FGFR alterations) and C (US only; negative for FGF/FGFR alterations) can be 
stopped if 1 or less responders are observed within the first 10 subjects who have at least 2 cycles of data.  
This is just a guidance and nonbinding. 
Data Monitoring Committee:   
No independent Data Monitoring Committee is planned for this study.  A study committee will be 
established and will include the investigators or designees, the sponsor representatives (eg, medical 
monitor), and when appropriate ad hoc experts. 


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TABLE OF CONTENTS 
SYNOPSIS ......................................................................................................................................3 
LIST OF ABBREVIATIONS ........................................................................................................13 
1. 
INTRODUCTION ......................................................................................................15 
1.1. 
Background .................................................................................................................15 
1.1.1. 
Fibroblast Growth Factor Receptor Inhibition in Oncology .......................................15 
1.1.2. 
Cholangiocarcinoma ...................................................................................................16 
1.2. 
Study Rationale ...........................................................................................................17 
1.3. 
Potential Risks and Benefits of the Treatment Regimen ............................................18 
1.3.1. 
Potential Risks of INCB054828 Based on Preclinical Safety ....................................18 
1.3.2. 
Potential Risks of INCB054828 Based on Clinical Safety .........................................19 
1.3.2.1. 
Pharmacokinetic/Pharmacodynamic Summary ..........................................................23 
1.3.3. 
Phototoxicity ...............................................................................................................25 
2. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................25 
2.1. 
Study Objectives .........................................................................................................25 
2.1.1. 
Primary Objective .......................................................................................................25 
2.1.2. 
Secondary Objectives .................................................................................................25 
 
25 
2.2. 
Study Endpoints ..........................................................................................................25 
2.2.1. 
Primary Endpoint ........................................................................................................25 
2.2.2. 
Secondary Endpoints ..................................................................................................26 
 
26 
3. 
SUBJECT ELIGIBILITY ...........................................................................................27 
3.1. 
Subject Inclusion Criteria ...........................................................................................27 
3.2. 
Subject Exclusion Criteria ..........................................................................................28 
4. 
INVESTIGATIONAL PLAN .....................................................................................30 
4.1. 
Overall Study Design ..................................................................................................30 
4.2. 
Measures Taken to Avoid Bias ...................................................................................31 
4.3. 
Number of Subjects ....................................................................................................32 
4.3.1. 
Planned Number of Subjects ......................................................................................32 
4.3.2. 
Replacement of Subjects .............................................................................................32 
4.4. 
Duration of Treatment and Subject Participation .......................................................32 


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4.5. 
Overall Study Duration ...............................................................................................32 
4.6. 
Study Termination ......................................................................................................32 
5. 
TREATMENT ............................................................................................................33 
5.1. 
Treatment Assignment ................................................................................................33 
5.1.1. 
Subject Numbering and Treatment Assignment .........................................................33 
5.1.2. 
Randomization and Blinding ......................................................................................33 
5.2. 
Study Drug ..................................................................................................................33 
5.2.1. 
INCB054828 ...............................................................................................................33 
5.2.1.1. 
Description and Administration ..................................................................................33 
5.2.1.2. 
Supply, Packaging, and Labeling ...............................................................................33 
5.2.1.3. 
Storage ........................................................................................................................34 
5.2.1.4. 
Instruction to Subjects for Handling Study Drug (INCB054828) ..............................34 
5.3. 
Treatment Compliance ................................................................................................34 
5.4. 
Treatment Interruptions and Adjustments ..................................................................35 
5.4.1. 
Dose Modifications .....................................................................................................35 
5.4.2. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study 
Drug ............................................................................................................................35 
5.4.3. 
Management of Hyperphosphatemia ..........................................................................36 
5.4.4. 
Criteria for Permanent Discontinuation of Study Drug ..............................................37 
5.5. 
Withdrawal of Subjects From Study Treatment .........................................................37 
5.5.1. 
Withdrawal Criteria ....................................................................................................37 
5.5.2. 
Withdrawal Procedures ...............................................................................................38 
5.6. 
Withdrawal of Subjects From Study ...........................................................................38 
5.7. 
Concomitant Medications ...........................................................................................38 
5.7.1. 
Restricted Medications ...............................................................................................38 
5.7.2. 
Prohibited Medications ...............................................................................................38 
6. 
STUDY ASSESSMENTS ..........................................................................................38 
6.1. 
Prescreening and Screening ........................................................................................43 
6.2. 
Treatment ....................................................................................................................43 
6.3. 
End of Treatment ........................................................................................................43 
6.4. 
Follow-Up ...................................................................................................................44 
6.4.1. 
Safety Follow-Up ........................................................................................................44 
6.4.2. 
Disease Status Follow-Up ...........................................................................................44 


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6.4.3. 
Survival Follow-Up ....................................................................................................44 
6.5. 
End of Study ...............................................................................................................44 
6.6. 
Unscheduled Visits .....................................................................................................44 
7. 
CONDUCT OF STUDY ASSESSMENTS AND PROCEDURES ...........................45 
7.1. 
Administration of Informed Consent Form ................................................................45 
7.2. 
Interactive Response Technology Procedure ..............................................................45 
7.3. 
Demography and Medical History ..............................................................................45 
7.3.1. 
Demographics and General Medical History .............................................................45 
7.3.2. 
Disease Characteristics and Treatment History ..........................................................45 
7.4. 
Prior and Concomitant Medications and Procedures ..................................................45 
7.5. 
Safety Assessments .....................................................................................................45 
7.5.1. 
Adverse Events ...........................................................................................................45 
7.5.2. 
Physical Examinations ................................................................................................46 
7.5.2.1. 
Comprehensive Physical Examination .......................................................................46 
7.5.2.2. 
Targeted Physical Examination ..................................................................................46 
7.5.3. 
Vital Signs ..................................................................................................................46 
7.5.4. 
Electrocardiograms .....................................................................................................46 
7.5.5. 
Comprehensive Eye Examination...............................................................................47 
7.5.6. 
Laboratory Assessments .............................................................................................47 
7.5.6.1. 
Pregnancy Testing ......................................................................................................47 
7.5.6.2. 
Hepatitis Screening Tests ...........................................................................................47 
7.5.6.3. 
HIV Screening Tests ...................................................................................................47 
7.5.6.4. 
Evaluation of FGF and FGFR Genetic Alterations ....................................................47 
7.6. 
Efficacy Assessments .................................................................................................48 
7.6.1. 
Tumor Imaging ...........................................................................................................48 
7.6.2. 
Eastern Cooperative Oncology Group Performance Status ........................................48 
 
48 
7.6.4. 
Survival Follow-Up ....................................................................................................48 
7.7. 
Pharmacokinetic Assessments ....................................................................................49 
7.7.1. 
Blood Sample Collection ............................................................................................49 
 
49 
 
49 
 
49 


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49 
 
50 
8. 
SAFETY MONITORING AND REPORTING .........................................................50 
8.1. 
Adverse Events ...........................................................................................................50 
8.1.1. 
Definitions ..................................................................................................................50 
8.1.2. 
Reporting ....................................................................................................................50 
8.2. 
Laboratory Test Abnormalities ...................................................................................52 
8.3. 
Serious Adverse Events ..............................................................................................52 
8.3.1. 
Definitions ..................................................................................................................52 
8.3.2. 
Reporting ....................................................................................................................53 
8.4. 
Emergency Unblinding of Treatment Assignment .....................................................54 
8.5. 
Pregnancy ...................................................................................................................54 
8.6. 
Warnings and Precautions ..........................................................................................55 
8.7. 
Data Monitoring Committee .......................................................................................55 
8.8. 
Product Complaints ....................................................................................................55 
9. 
STATISTICS ..............................................................................................................55 
9.1. 
Study Populations .......................................................................................................55 
9.2. 
Selection of Sample Size ............................................................................................55 
9.3. 
Level of Significance ..................................................................................................56 
9.4. 
Statistical Analyses .....................................................................................................56 
9.4.1. 
Efficacy Analyses .......................................................................................................56 
9.4.1.1. 
Primary Efficacy Analyses .........................................................................................56 
9.4.1.2. 
Secondary Efficacy Analyses .....................................................................................56 
 
57 
9.4.2. 
Safety Analyses ..........................................................................................................57 
9.4.2.1. 
Adverse Events ...........................................................................................................57 
9.4.2.2. 
Clinical Laboratory Tests ...........................................................................................57 
9.4.2.3. 
Vital Signs ..................................................................................................................58 
9.4.2.4. 
Electrocardiograms .....................................................................................................58 
9.4.3. 
Pharmacokinetic Analysis ..........................................................................................58 
9.5. 
Analyses for the Data Monitoring Committee ............................................................58 
9.6. 
Futility Analysis..........................................................................................................58 


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10. 
ETHICAL CONSIDERATIONS AND ADMINISTRATIVE 
PROCEDURES ..........................................................................................................59 
10.1. 
Investigator Responsibilities .......................................................................................59 
10.2. 
Accountability, Handling, and Disposal of Study Drug .............................................60 
10.3. 
Data Management .......................................................................................................61 
10.4. 
Data Privacy and Confidentiality of Study Records ...................................................61 
10.5. 
Financial Disclosure ...................................................................................................62 
10.6. 
Publication Policy .......................................................................................................62 
11. 
REFERENCES ...........................................................................................................63 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS ...............................................................................66 
APPENDIX B. CYP3A4 INDUCERS AND INHIBITORS ......................................................67 
APPENDIX C. PHARMACOKINETIC ANALYTICAL PARAMETERS ..............................70 
APPENDIX D. FGF/FGFR ALTERATIONS ............................................................................71 
APPENDIX E. PROTOCOL AMENDMENT SUMMARY OF CHANGES ............................74 
 


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LIST OF TABLES 
Table 1: 
Subject Exposure in Study INCB 54828-101 .............................................................19 
Table 2: 
Summary of Treatment-Emergent Adverse Events Occurring in ≥ 5% of 
Subjects in Decreasing Order of Frequency for Parts 1 and 2 Combined 
(INCB054828 Monotherapy, Study INCB 54828-101) .............................................21 
Table 3: 
Guidelines for Interruption and Restarting of Study Drug .........................................35 
Table 4: 
Recommended Approach for Hyperphosphatemia Management ...............................36 
Table 5: 
Study Assessments......................................................................................................39 
Table 6: 
Laboratory Assessments .............................................................................................41 
Table 7: 
Laboratory Tests:  Required Analytes ........................................................................42 
Table 8: 
ECOG Performance Status .........................................................................................48 
Table 9: 
Criteria for Clinically Notable Vital Sign Abnormalities ...........................................58 
Table 10: Criteria for Clinically Notable Electrocardiogram Abnormalities .............................58 
 
LIST OF FIGURES 
Figure 1: 
INCB054828 Plasma Concentrations (Mean ± SE) at Steady State After 
13.5 mg QD Oral Doses of INCB054828 ...................................................................24 
Figure 2: 
Serum Phosphate Versus Exposure ............................................................................24 
Figure 3: 
Study Design ...............................................................................................................31 


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LIST OF ABBREVIATIONS 
The following abbreviations and special terms are used in this clinical study Protocol. 
Abbreviation 
Definition 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
CFR 
Code of Federal Regulations 
CNS 
central nervous system 
CR 
complete response 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
D/C 
discontinue 
DCR 
disease control rate 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
 
 
EOT 
end of treatment 
FDA 
Food and Drug Administration 
FGF 
fibroblast growth factor 
FGFR 
fibroblast growth factor receptor 
GCP 
Good Clinical Practice 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HDL 
high-density lipoprotein 
HED 
human equivalent dose 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HP 
hyperphosphatemia 
ICF 
informed consent form  
ICH 
International Conference on Harmonisation 
IEC 
independent ethics committee 
IN 
Investigator Notification 
INR 
international normalized ratio 
IRB 
institutional review board 


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Abbreviation 
Definition 
IRT 
interactive response technology 
LDL 
low-density lipoprotein 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
NCI 
National Cancer Institute 
NOAEL 
no-observed-adverse-effect level 
OCT 
optic coherence tomography   
ORR 
objective response rate 
OS 
overall survival 
PD 
progressive disease 
PFS 
progression-free survival 
PK 
pharmacokinetics 
PR 
partial response 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
QD 
once daily 
 
 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RNA 
ribonucleic acid 
RPED 
retinal pigmented epithelium detachment 
SAE 
serious adverse event 
SD 
stable disease 
SF 
screen fail 
SRD 
serous retinal detachment 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
WBC 
white blood cell 
 


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1. 
INTRODUCTION 
1.1. 
Background 
INCB054828 is an inhibitor of the fibroblast growth factor receptor (FGFR) family of receptor 
tyrosine kinases that is proposed for the treatment of cholangiocarcinoma.  Aberrant signaling 
through FGFR resulting from gene amplification or mutation, chromosomal translocation, and 
ligand-dependent activation of the receptors has been demonstrated in multiple types of human 
cancers.  Fibroblast growth factor receptor signaling contributes to the developing of 
malignancies by promoting tumor cell proliferation, survival, migration, and angiogenesis.  
Incyte is proposing to study INCB054828 for the treatment of advanced/metastatic or surgically 
unresectable cholangiocarcinoma.  Refer to the Investigator's Brochure (IB) for additional 
background information on INCB054828. 
1.1.1. 
Fibroblast Growth Factor Receptor Inhibition in Oncology 
The mammalian FGFR family is composed of 4 highly conserved receptors (FGFR1, FGFR2, 
FGFR3, and FGFR4) that have an extracellular ligand binding domain, a single transmembrane 
domain, and an intracellular tyrosine kinase domain.  Eighteen fibroblast growth factor (FGR) 
ligands, divided into canonical and hormonal FGFRs, bind to FGFRs leading to receptor 
dimerization, activation of the kinase domain, and transphosphorylation of the receptors 
(Eswarakumar et al 2005).  Subsequent signal transduction occurs through phosphorylation of 
substrate proteins such as FGFR substrate 2 that leads to activation of the 
RAS-mitogen-activated protein kinase and phosphoinositide 3-kinase–protein kinase B pathways 
and phospholipase Cγ that activates the protein kinase C pathway.  In some cellular context, 
signal transducer and activator of transcription proteins are also activated by FGFRs.  Signaling 
through the FGF-FGFR pathway is tightly controlled through feedback regulation.  
Mitogen-activated protein kinase phosphatases and Sprouty proteins are upregulated upon FGFR 
stimulation and antagonize FGF-dependent activation of extracellular signal-regulated kinases.  
In many cases, FGFR pathway activation promotes cell proliferation, survival, and migration; 
however, cellular context plays an important role, and in certain tissues, FGFR signaling results 
in growth arrest and cellular differentiation (Dailey et al 2005). 
In adults, FGF-FGFR signaling is involved in angiogenesis during wound healing.  The 
hormonal FGF ligands contribute to regulation of metabolic pathways involving lipid, glucose, 
phosphate, and vitamin D (Itoh 2010).  Genetic defects in the FGF23-signaling pathway lead to 
disordered phosphate metabolism:  loss of function mutations in FGF23 or its signaling result in 
retention of phosphate and tissue mineralizing, while gain of function mutations in the FGF23 
pathway manifests as hypophosphatemic Rickets syndrome (Farrow and White 2010). 
There is strong genetic and functional evidence that dysregulation of FGFR can lead to the 
establishment and progression of cancer.  Genetic alterations in FGFR1, FGFR2, and FGFR3 
have been described in many tumor types (Knights and Cook 2010, Turner and Grose 2010).  
These include activating mutations, translocations, and gene amplification resulting in ligand 
independent, constitutive activation of the receptors or aberrant ligand-dependent signaling 
through FGFRs.   


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Dysregulation of FGF ligands has also been reported in many human cancers.  Preclinical studies 
have shown that high levels of FGF ligands such as FGF2 promote cancer cell resistance to 
radiation, chemotherapeutics, and targeted cancer drugs (Fuks et al 1994, Pardo et al 2002, 
Terai et al 2013).  Clinically, detection of high levels of FGF2 in tumors is associated with 
poorer outcome in several tumor types including NSCLC (Donnem et al 2009, Rades et al 2012). 
A substantial body of evidence supports that genetically activated FGFR pathway sensitizes 
FGFR-altered cancer cells to knockdown or inhibition of these receptors (Kunii et al 2008, 
Qing et al 2009, Weiss et al 2010, Lamont et al 2011).  A large screen of more than 500 tumor 
cell lines with a selective FGFR inhibitor demonstrated that only a small percentage (5.9%) of all 
cells are sensitive to FGFR inhibition, and growth suppressed cell lines were highly enriched for 
FGFR alterations (Guagnano et al 2012).  These results demonstrate that FGFR inhibitors are 
active in a targeted manner against cancers with activated FGFR pathway.  An implication of 
these data is that selection based on molecular-, genetic-, or protein-based diagnostic tests for 
specific FGFR alterations in tumors may be important for identifying patients most likely to 
benefit from an FGFR inhibitor. 
Results from early clinical studies of selective FGFR inhibitors, including INCB054828 have 
shown a tolerable safety profile for the class and preliminary signs of clinical benefit in subjects 
with FGF/FGFR alterations.  An on-target pharmacologic effect of FGFR inhibition in clinical 
studies is hyperphosphatemia (HP).  In the ongoing INCB 54828-101 study,  at the 
recommended Phase 2 dose (RP2D) of 13.5 mg, 100% of subjects developed HP (> 5.5 mg/mL).  
Hyperphosphatemia has been managed with diet modifications and phosphate binders.   
INCB054828 is a potent selective inhibitor of FGFR1, FGFR2, and FGFR3 and is proposed for 
the treatment of subjects with advanced/metastatic or surgically unresectable 
cholangiocarcinoma who have FGFR2 translocation, have other FGF/FGFR alteration, or are 
negative for FGF/FGFR alterations. 
1.1.2. 
Cholangiocarcinoma 
Cholangiocarcinoma, also known as bile duct carcinoma, is found in the intra- or extrahepatic 
bile ducts.  It is the second most common primary liver cancer but only accounts for 
approximately 3% of all gastrointestinal cancers (Rizvi and Gores 2013).  First line therapy is 
typically gemcitabine and cisplatin with a response rate of 30% to 50% (Eckman et al 2011) and 
the 5-year survival rate is 11.5% (NCI 2016). 
The incidence of cholangiocarcinoma is quite rare, with 1 to 2 patients per 100,000 in regions 
like the US and the UK; however in regions like Southeast Asia, liver fluke and other parasitic 
infections give rise to a much higher incidence (113 per 100,000; Bergquist and von Seth 2015). 
Fibroblast growth factor receptor 2 translocations are the most common FGFR alteration in 
cholangiocarcinoma and associated with a more indolent disease state (Churi et al 2014, Wu et al 
2013).  These fusions are found in 13% to 15% of patients with intrahepatic cholangiocarcinoma 
(Graham et al 2014).  Intrahepatic disease accounts for 5% of all cholangiocarcinoma, with 95% 
of patients having extrahepatic disease (Blechacz and Gores 2008) however recent data indicates 
a rise in intrahepatic disease (Bergquist and von Seth 2015).  Other FGF/FGFR alterations are 
not as common but can be found in the extrahepatic cholangiocarcinoma patients (Bergquist and 
von Seth 2015). 


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1.2. 
Study Rationale 
Cancer has several common characteristics that can be observed across numerous tumor types.  
One common characteristic is the uncontrolled growth and survival of cells and their ability to 
become invasive throughout the body.  Fibroblast growth factor signaling produces mitogenic, 
antiapoptotic, and angiogenic responses in cells, which leads to a deregulated state.  Evidence 
from several in vitro and in vivo tumor models has established the FGFs and FGFRs as 
oncogenes and their expression has been found in numerous solid tumors or hematological 
malignancies.  Several genetic alterations have been shown to generate overexpression of the 
FGF receptor, produce a receptor that is constitutively active, or lead it to a state where there is 
reduced dependence on ligand binding for activation (Knights and Cook 2010). 
Tyrosine kinases are an especially important target in cancer therapy as they have a key role in 
growth factor signaling.  Several tyrosine kinase inhibitors have been shown to be effective 
antitumor agents and have been approved in multiple oncology indications (Arora and Scholar 
2005).  INCB054828 is a potent inhibitor of the kinase activity of FGFR1, FGFR2, and FGFR3 
and has been shown to inhibit growth in several tumor models.   
The planned study will evaluate the efficacy, safety, and tolerability of INCB054828 in subjects 
with advanced/metastatic or surgically unresectable cholangiocarcinoma with FGFR2 
translocations, FGF/FGFR alterations and without FGF/FGFR alterations.  Subjects with FGFR2 
translocations are found in approximately 15% of subjects with intrahepatic cholangiocarcinoma 
(Arai et al 2013, Ross et al 2014, Ang 2015). 
Preliminary data from the ongoing Phase 1 study INCB54828-101 has shown a tolerable safety 
profile and signs of efficacy in tumors that have FGF/FGFR genetic alterations.  In the ongoing 
Phase 1 study, more than 25 subjects have been treated at dose levels ranging from 1 to 20 mg 
once daily for 2 weeks followed by 1 week off in 21-day cycles.  The recommended Phase 2 
starting dose has been established at 13.5 mg once daily following the 2 weeks on/1 week off 
regimen.  This dose was recommended based on safety, pharmacokinetics (PK), and preliminary 
signals of clinical benefit.  One subject with FGFR2-CCDC6 cholangiocarcinoma has been 
treated with 9 mg of INCB054828 with a confirmed partial response (PR). 
In addition, a Phase 2 study of BGJ398 in subjects with FGFR-altered cholangiocarcinoma, the 
most frequently reported adverse event (AE) was HP, followed by fatigue, stomatitis, and 
alopecia.  Hyperphosphatemia was the leading dose-limiting toxicity resulting in interruptions 
and discontinuations.  The efficacy results of this compound in the ongoing Phase 2 study have 
shown an overall response rate of 18.8% among 48 subjects with FGFR2 fusions (Javle et al 
2018). 
Amendment 5 (03 OCT 2017) increases the number of subjects enrolled into Cohort A (FGFR2 
translocation) from 60 to 100 subjects.  The rationale for increasing the number of subjects 
enrolled into this cohort is to assure the most robust efficacy data to inform future development 
decisions.  As the primary analysis will be based solely on Cohort A, this amendment does not 
increase the number of subjects in Cohorts B and C.  Futility analysis will be performed as 
initially planned (before Amendment 5), when approximately 25 subjects are enrolled into 
Cohort A and have at least 1 tumor assessment or have permanently discontinued study 
treatment. 
See Section 9 for the impact on reporting of the primary endpoint. 


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1.3. 
Potential Risks and Benefits of the Treatment Regimen 
1.3.1. 
Potential Risks of INCB054828 Based on Preclinical Safety 
The most prominent findings following repeat-dose exposure to INCB054828 in both rats and 
monkeys were HP, physeal dysplasia, and soft tissue mineralization.  Mineralization was 
observed in numerous tissues including the kidney, stomach, arteries (gastric and pulmonary), 
ovaries (monkey only), and eyes (cornea; rat only).  Soft tissue mineralization was not reversible, 
while physeal and cartilage findings were reversible.  
Hyperphosphatemia, physeal dysplasia, and soft tissue mineralization have been reported in 
rodents and large animals following administration of selective FGFR inhibitors (Brown et al 
2005, Brown 2010, Wöhrle et al 2011, Yanochko et al 2013).  These observations can be 
explained by the pharmacological action of FGFR inhibition.  Fibroblast growth factor 23 (FGF 
23)–mediated signaling negatively affects renal vitamin D biosynthesis by transcriptional 
repression of CYP27B1, which catalyzes the production of the biologically active vitamin D 
metabolite 1,25(OH)2D3, and by induction of CYP24A1, which converts 1,25(OH)2D3 into a 
metabolite that is less biologically active.  Additionally, it has been published that FGF-23 
suppresses renal phosphate reabsorption by decreasing the expression of the sodium-phosphate 
cotransporters NPT2A and NPT2C in the brush-border membrane of proximal tubule epithelial 
cells (Baum et al 2005, Shimada et al 2001, Shimada et al 2004a, Shimada et al 2004b).  
Wöhrle et al (2011) demonstrated that FGFR inhibition by oral administration of PD176067 
counteracts the biologic activity of FGF-23 in the kidney, leading to HP and hypervitaminosis D. 
In rats, the mineralization was similar in distribution and morphology to that occasionally 
observed in normal animals; thus it is likely that the increased incidence of mineralization in 
various tissues at these doses represents a test article–related exacerbation of a spontaneously 
occurring condition.  While soft tissue mineralization was not reversible during 28-day recovery 
period, there was also no evidence of progression or worsening of this effect.  Soft tissue 
mineralization in monkeys was observed only at 3 mg/kg per day in the 10-day range-finding 
study and was not assessed for reversibility.  No evidence of mineralization was found at the 
doses tested in the 28-day study in monkeys. 
Moderate lens opacities (capsule, posterior) in one 0.33 mg/kg per day and one 1 mg/kg per day 
males and slight attenuation of retinal vessels in one 1 mg/kg per day female were observed in 
monkeys at the end-of-treatment (EOT) period on the 28-day Good Laboratory Practice study.  
These findings were not present during the pretest period and thus a relationship to INCB054828 
cannot be dismissed.  However, lens opacities are occasionally observed in normal cynomolgus 
monkeys of similar age and origin according to the testing facility historical control data.  
Persistence of lens opacity in 1 animal at the end of recovery period suggests that this finding is 
not reversible. 
Fully reversible mild-to-moderate elevation of alanine aminotransferase (ALT) and aspartate 
aminotransferase (AST) were noted at the EOT period in the 28-day monkey study at doses 
≥ 0.33 mg/kg per day; these changes were not associated with changes in other hepatobiliary 
parameters or microscopic changes in the liver.  These changes may be related to FGFR4 
inhibition, which is known to result in increases in liver function tests without histological 
correlates (Pai et al 2012). 


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In the 28-day study in rats, no severe toxicity was observed; the no-observed-adverse-effect level 
(NOAEL) was determined as 1.05 mg/kg per day (6.3 mg/m2 per day), the highest dose tested.  
The human equivalent dose (HED) associated with 1.05 mg/kg per day based on standard body 
surface area conversion is 10.1 mg.  In the 28-day monkey study, no severe toxicity was 
observed.  The NOAEL was considered to be 1 mg/kg per day (12 mg/m2 per day), the highest 
dose tested.  The HED associated with 1 mg/kg per day based on standard body surface area 
conversion is 19.2 mg.   
More information can be found in the IB. 
1.3.2. 
Potential Risks of INCB054828 Based on Clinical Safety 
The recommended Phase 2 dose has been selected based from the INCB 54828-101 study, which is 
the first clinical study being conducted with INCB054828.  Doses ranging from 1 mg to 20 mg 
once daily (QD) have been evaluated to date.  Pharmacokinetics and pharmacodynamics have 
been evaluated in each of these cohorts to assess the extent of target inhibition, which in turn was 
used along with the safety data to select a dose for Phase 2 studies. 
Of the 60 subjects who have been enrolled into Study INCB 54828-101 as of the data cutoff date 
(25 NOV 2016), 22 subjects have been administered INCB054828 in Part 1 (monotherapy dose 
escalation), 21 subjects in Part 2 (monotherapy dose expansion), and 17 subjects in Part 3 
(combination therapy).  The duration of treatment with INCB054828 in Part 1 and Part 2 
combined and Part 3 ranged from 1 to 49 weeks and from 2 to 27 weeks, respectively.  Subject 
exposure is presented in Table 1.  The monotherapy maximum tolerated dose has not been 
reached in Part 1.  The maximum safely administered dose was 20 mg.  One dose-limiting 
toxicity (Grade 3 stomatitis) was observed at 20 mg.  The recommended Part 2 dose has been 
determined at 13.5 mg based on pharmacodynamic and clinical effect. 
Table 1: 
Subject Exposure in Study INCB 54828-101 
Treatment 
Number of Subjects 
Minimum 
(Weeks) 
Maximum 
(Weeks) 
Total number of subjects exposed to INCB054828  
60 
1 
49 
INCB054828 monotherapy:  Part 1 
22 
1 
44 
1 mg, 2 mg, 4 mga 
3 
2 
8 
6 mg 
4 
2 
14 
9 mg 
3 
8 
44 
13.5 mg 
6 
5 
17 
20 mg 
6 
1 
20 
INCB054828 monotherapy:  Part 2 
21 
1 
49 
9 mg 
3 
17 
49 
13.5 mg 
18 
1 
26 
INCB054828 in combination:  Part 3 
17 
2 
27 
INCB054828 9 mg + pembrolizumab 
3 
4 
10 
INCB054828 13.5 mg + pembrolizumab 
5 
2 
27 
INCB054828 13.5 mg + gemcitabine + cisplatin 
4 
4 
20 
INCB054828 13.5 mg + docetaxel 
5 
6 
16 
a One subject at each dose. 


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In Parts 1 and 2 combined of Study INCB 54828-101, the most frequently reported treatment-
emergent AE (TEAE) was HP (48.8%; serum phosphate > 5.5 mg/dL), which is expected from 
inhibition of FGFR signaling and is used as a pharmacodynamic measure in the study.  
Treatment-emergent adverse events, regardless of causality, occurring in ≥ 5% of subjects are 
presented in Table 2.  Eighteen subjects (41.9%) had ≥ Grade 3 TEAEs, 7 of which were 
considered related to INCB054828 by the investigator:  fatigue and palmar-plantar 
erythrodysesthesia syndrome (9 mg dose); convulsion, fatigue, onycholysis, paronychia, and 
stomatitis (13.5 mg dose); and stomatitis and palmar-plantar erythrodysesthesia syndrome 
(20 mg dose). 
Thirteen subjects experienced 21 serious AEs (SAEs).  Serious AEs that occurred in more than 
1 subject were pneumonia (9.3%) and disease progression (4.7%).  In the 13.5 mg dose cohort, 
1 SAE of seizure was considered related to study drug by the investigator; the subject was 
hospitalized, received treatment for the seizure, the event resolved, and the subject subsequently 
died due to disease progression.  Additionally, the subject had underlying history of cardiovascular 
disease, hypertension, and orthostatic hypotension.  No other SAEs were considered related to 
study drug.  Four subjects had fatal events:  disease progression (2 subjects), pneumonia, and 
intracranial hemorrhage (1 subject each). 
Nine SAEs in 6 subjects in Part 1 and Part 2 were identified from the safety database.  In the 
9 mg dose cohort, 1 subject had SAEs of dyspnea and musculoskeletal chest pain.  In the 
13.5 mg cohort, 1 subject had 2 SAEs of pneumonia and 1 SAE of atrial fibrillation, and 
3 subjects had SAEs of systemic inflammatory response syndrome, disease progression, and 
vomiting (1 subject per event).  In the 20 mg cohort, 1 subject had an SAE of pulmonary 
embolism.  The SAE of disease progression was fatal.  None of the SAEs were considered 
related to INCB054828 by the investigator. 
One subject, receiving 4 mg of INCB054828, permanently discontinued treatment of 
INCB054828 because of a TEAE (depressed level of consciousness due to progressive disease of 
the brain). 


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Table 2: 
Summary of Treatment-Emergent Adverse Events Occurring in ≥ 5% of Subjects in Decreasing Order of 
Frequency for Parts 1 and 2 Combined (INCB054828 Monotherapy, Study INCB 54828-101) 
MedDRA Preferred Term 
INCB054828 
Total No. of Subjects (%)  
(N = 43) 
1/2/4 mg 
(N = 3) 
6 mg 
(N = 4) 
9 mg 
(N = 6) 
13.5 mg 
(N = 24) 
20 mg 
(N = 6) 
Hyperphosphatemia 
0 (0.0) 
1 (25.0) 
3 (50.0) 
13 (54.2) 
4 (66.7) 
21 (48.8) 
Fatigue 
1 (33.3) 
1 (25.0) 
4 (66.7) 
11 (45.8) 
2 (33.3) 
19 (44.2) 
Dry mouth 
0 (0.0) 
1 (25.0) 
2 (33.3) 
6 (25.0) 
2 (33.3) 
11 (25.6) 
Alopecia 
0 (0.0) 
0 (0.0) 
3 (50.0) 
5 (20.8) 
1 (16.7) 
9 (20.9) 
Diarrhea 
0 (0.0) 
1 (25.0) 
1 (16.7) 
4 (16.7) 
2 (33.3) 
8 (18.6) 
Stomatitis 
0 (0.0) 
0 (0.0) 
1 (16.7) 
3 (12.5) 
4 (66.7) 
8 (18.6) 
Anemia 
1 (33.3) 
0 (0.0) 
1 (16.7) 
4 (16.7) 
1 (16.7) 
7 (16.3) 
Decreased appetite 
0 (0.0) 
2 (50.0) 
1 (16.7) 
4 (16.7) 
0 (0.0) 
7 (16.3) 
Dehydration 
1 (33.3) 
1 (25.0) 
0 (0.0) 
4 (16.7) 
1 (16.7) 
7 (16.3) 
Dysgeusia 
1 (33.3) 
0 (0.0)) 
2 (33.3) 
2 (8.3) 
2 (33.3) 
7 (16.3) 
Vision blurred 
1 (33.3) 
1 (25.0) 
2 (33.3) 
2 (8.3) 
1 (16.7) 
7 (16.3) 
Weight decreased 
2 (66.7) 
0 (0.0) 
1 (16.7) 
2 (8.3) 
1 (16.7) 
6 (14.0) 
Constipation 
0 (0.0) 
0 (0.0) 
0 (0.0) 
5 (20.8) 
0 (0.0) 
5 (11.6) 
Cough 
1 (33.3) 
0 (0.0) 
0 (0.0) 
3 (12.5) 
1 (16.7) 
5 (11.6) 
Epistaxis 
0 (0.0) 
0 (0.0) 
1 (16.7) 
3 (12.5) 
1 (16.7) 
5 (11.6) 
Nausea 
1 (33.3) 
1 (25.0) 
1 (16.7) 
2 (8.3) 
0 (0.0) 
5 (11.6) 
Pain in extremity 
0 (0.0) 
1 (25.0) 
2 (33.3) 
1 (4.2) 
1 (16.7) 
5 (11.6) 
Abdominal pain 
0 (0.0) 
0 (0.0) 
1 (16.7) 
3 (12.5) 
0 (0.0) 
4 (9.3) 
Aspartate aminotransferase increased 
1 (33.3) 
0 (0.0) 
0 (0.0) 
3 (12.5) 
0 (0.0) 
4 (9.3) 
Back pain 
1 (33.3) 
0 (0.0) 
2 (33.3) 
1 (4.2) 
0 (0.0) 
4 (9.3) 
Dry eye 
0 (0.0) 
0 (0.0) 
0 (0.0) 
3 (12.5) 
1 (16.7) 
4 (9.3) 
Dyspnea 
0 (0.0) 
1 (25.0) 
0 (0.0) 
1 (4.2) 
2 (33.3) 
4 (9.3) 
Hyponatremia 
0 (0.0) 
0 (0.0) 
1 (16.7) 
2 (8.3) 
1 (16.7) 
4 (9.3) 
Hypophosphatemia 
0 (0.0) 
0 (0.0) 
1 (16.7) 
2 (8.3) 
1 (16.7) 
4 (9.3) 
Musculoskeletal pain 
0 (0.0) 
1 (25.0) 
1 (16.7) 
2 (8.3) 
0 (0.0) 
4 (9.3) 
Pneumonia 
0 (0.0) 
0 (0.0) 
2 (33.3) 
1 (4.2) 
1 (16.7) 
4 (9.3) 
Vomiting 
1 (33.3) 
0 (0.0) 
1 (16.7) 
2 (8.3) 
0 (0.0) 
4 (9.3) 


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Table 2: 
Summary of Treatment-Emergent Adverse Events Occurring in ≥ 5% of Subjects in Decreasing Order of 
Frequency for Parts 1 and 2 Combined (INCB054828 Monotherapy, Study INCB 54828-101) (Continued) 
MedDRA Preferred Term 
INCB054828 
Total No. of Subjects (%)  
(N = 43) 
1/2/4 mg 
(N = 3) 
6 mg 
(N = 4) 
9 mg 
(N = 6) 
13.5 mg 
(N = 24) 
20 mg 
(N = 6) 
Alanine aminotransferase increased 
1 (33.3) 
0 (0.0) 
0 (0.0) 
2 (8.3) 
0 (0.0) 
3 (7.0) 
Ascites 
0 (0.0) 
0 (0.0) 
0 (0.0) 
2 (8.3) 
1 (16.7) 
3 (7.0) 
Dyspepsia 
0 (0.0) 
0 (0.0) 
1 (16.7) 
2 (8.3) 
0 (0.0) 
3 (7.0) 
Hypercalcemia 
1 (33.3) 
0 (0.0) 
0 (0.0) 
2 (8.3) 
0 (0.0) 
3 (7.0) 
Hypoesthesia 
0 (0.0) 
1 (25.0) 
1 (16.7) 
0 (0.0) 
1 (16.7) 
3 (7.0) 
Hypoalbuminemia 
0 (0.0) 
0 (0.0) 
0 (0.0) 
3 (12.5) 
0 (0.0) 
3 (7.0) 
Hypokalemia 
1 (33.3) 
1 (25.0) 
1 (16.7) 
0 (0.0) 
0 (0.0) 
3 (7.0) 
Pain 
0 (0.0) 
1 (25.0) 
0 (0.0) 
1 (4.2) 
1 (16.7) 
3 (7.0) 
Paronychia 
0 (0.0) 
0 (0.0) 
0 (0.0) 
2 (8.3) 
1 (16.7) 
3 (7.0) 
Upper respiratory tract infection 
1 (33.3) 
0 (0.0) 
0 (0.0) 
1 (4.2) 
1 (16.7) 
3 (7.0) 
Vitamin D deficiency 
0 (0.0) 
0 (0.0) 
1 (16.7) 
2 (8.3) 
0 (0.0) 
3 (7.0) 
Wheezing 
0 (0.0) 
1 (25.0) 
0 (0.0) 
1 (4.2) 
1 (16.7) 
3 (7.0) 
Note:  Subjects were counted once under each MedDRA preferred term.  Adverse events are ordered by the descending frequency in total column. 
Note:  Treatment-emergent adverse events are any AEs either reported for the first time or worsening of a pre-existing event after first dose of study medication. 
 


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In Part 3 of Study INCB 54828-101, the most frequently reported TEAE was HP (58.8%; serum 
phosphate > 5.5 mg/dL).  Other TEAEs, regardless of causality, occurring in 2 or more subjects 
are presented in the IB (version 3, Table 17).  Eight subjects (47.1%) had ≥ Grade 3 TEAEs, 
3 of which were considered related to INCB054828 by the investigator:  neutropenia in the 
docetaxel + INCB054828 13.5 mg cohort (Grade 4), ALT increased in the gemcitabine + 
cisplatin + INCB054828 13.5 mg cohort (Grade 3), and platelet count decreased in the 
gemcitabine + cisplatin + INCB054828 9 mg cohort (Grade 3). 
Seven subjects had 13 SAEs.  In the gemcitabine + cisplatin + INCB054828 cohorts, the SAEs 
were constipation and febrile neutropenia (INCB054828 9 mg) and disease progression, 
esophageal candidiasis, dehydration, and acute renal failure (INCB054828 13.5 mg).  In the 
docetaxel + INCB054828 13.5 mg cohort, the SAEs were anemia, tumor hemorrhage, and 
abdominal pain.  In the pembrolizumab + INCB054828 cohort, the SAEs were completed suicide 
(INCB054828 9 mg), and gastrointestinal hemorrhage, and hypotension (INCB054828 13.5 mg 
each subject).  No SAEs occurred in more than 1 subject, and no SAEs were considered related 
to INCB054828 by the investigator.  Two subjects had fatal events in Part 3:  completed suicide 
(pembrolizumab + INCB054828 9 mg) and disease progression (gemcitabine + cisplatin + 
INCB054828 13.5 mg). 
In Part 3, 3 SAEs in 3 subjects were identified from the safety database.  In the docetaxel + 
INCB054828 13.5 mg cohort, 1 subject had an SAE of enterocolitis, and another subject had an 
SAE of pulmonary embolism.  One subject in the pembrolizumab + INCB054828 cohort had an 
SAE of femur fracture.  None of the SAEs were considered related to INCB054828 by the 
investigator. 
One subject permanently discontinued treatment of INCB054828 in the gemcitabine + cisplatin 
+ INCB054828 13.5 mg cohort because of TEAEs (disease progression and acute renal failure). 
1.3.2.1. 
Pharmacokinetic/Pharmacodynamic Summary 
INCB054828 exhibited linear PK over the dose range evaluated, with rapid oral absorption and a 
biphasic elimination, with a terminal half-life range of 10.9 to 31.4 hours.  The projected average 
inhibition of FGFR2 based on PK and in vitro potency of INCB054828 ranged from 41% at 
1 mg to 97% at 20 mg.  Consistent with this projection, the observed inhibition of pFGFR2 in 
KATOIII cells spiked to ex vivo whole blood samples collected from subjects at trough was 82% 
after the 13.5 mg QD dose and 64% after the 9 mg QD dose.  The steady-state plasma 
concentrations of INCB054828 after 13.5 mg QD dose that exceeded in vivo IC50 over a 24-hour 
dosing period is showed in Figure 1.  The magnitude and frequency of HP was also dose-
dependent.  In the 9 mg cohort, 1 of 3 subjects developed HP in Part 1; 3 additional subjects were 
enrolled at 9 mg in Part 2.  Of a total of 6 subjects administered 9 mg, 4 experienced HP; in the 
13.5 mg cohort, all 6 subjects developed HP, which was managed with a low-phosphate diet and 
introduction of phosphate binders.  Further, the increase in serum phosphorus observed after 
treatment with INCB054828 was exposure-dependent (see Figure 2). 


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Figure 1: 
INCB054828 Plasma Concentrations (Mean ± SE) at Steady State After 
13.5 mg QD Oral Doses of INCB054828 
 
Figure 2: 
Serum Phosphate Versus Exposure 
 
Therefore, based on a manageable safety profile and a favorable PK/PD profile, the targeted 
starting dose for this Phase 2 is 13.5 mg.  This dose will be tested in 2 additional Phase 2 studies 
in subjects with bladder cancer (INCB 54828-201) and myeloproliferative neoplasms 
(INCB 54828-203). 
Subjects will be monitored on an ongoing basis throughout this study as per the schedules of 
assessments (Table 5 and Table 6). 


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1.3.3. 
Phototoxicity 
INCB054828 did not demonstrate phototoxic potential in preclinical studies (refer to the IB for 
more information).  As a result, no subject precautions are required to protect from 
sun/ultraviolet light. 
2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1. 
Study Objectives 
2.1.1. 
Primary Objective 
The primary objective of this study is to evaluate the efficacy of INCB054828 in subjects with 
advanced/metastatic or surgically unresectable cholangiocarcinoma with FGFR2 translocation 
who have failed at least 1 previous treatment. 
2.1.2. 
Secondary Objectives 
The secondary objectives are: 
• To evaluate the efficacy of INCB054828 in subjects with advanced/metastatic or 
surgically unresectable cholangiocarcinoma with different molecular subgroups.   
• To evaluate the safety of INCB054828 in subjects with advanced/metastatic or 
surgically unresectable cholangiocarcinoma. 
• To identify and evaluate covariates that may influence the PK of INCB054828 in this 
subject population through population PK analysis.  Additionally, exposure-response 
analyses for key efficacy and safety parameters will also be considered if sufficient 
data are available. 
2.2. 
Study Endpoints 
The genomic testing results from the central laboratory will be used to determine cohort 
allocation for primary and secondary endpoint analyses. 
2.2.1. 
Primary Endpoint 
The primary endpoint of this study is to determine the objective response rate (ORR) in subjects 
with FGFR2 translocations based on the central genomics laboratory results.  Objective response 
rate is defined as the proportion of subjects who achieved a complete response (CR; 
disappearance of all target lesions) or a PR (≥ 30% decrease in the sum of the longest diameters 


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of target lesions) based on RECIST v1.1.  Clinical response will be determined by an 
independent radiological review committee. 
2.2.2. 
Secondary Endpoints 
The secondary endpoints for this study include: 
• ORR in subjects with FGF/FGFR alterations other than FGFR2 translocations 
(Cohort B). 
• ORR in all subjects with FGF/FGFR alterations (Cohorts A and B). 
• ORR in subjects negative for FGF/FGFR alterations (Cohort C [US only]). 
• Progression-free survival (PFS = first dose to progressive disease [PD] or death; all 
cohorts). 
• Duration of response (DOR = time from the date of CR or PR until PD; all cohorts). 
• Disease control rate (DCR = CR + PR + stable disease [SD]; all cohorts). 
• Overall survival (OS = first dose to death of any cause; all cohorts). 
• Safety and tolerability will be assessed by evaluating the frequency, duration, and 
severity of AEs; through review of findings of physical examinations, changes in vital 
signs, and electrocardiograms (ECGs); and through clinical laboratory blood and 
urine sample evaluations (all cohorts). 
• Population PK (all cohorts). 


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3. 
SUBJECT ELIGIBILITY 
Deviations from eligibility criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability, and/or subject safety.  Therefore, 
adherence to the criteria as specified in the Protocol is essential. 
3.1. 
Subject Inclusion Criteria 
A subject who meets all of the following criteria may be included in the study: 
1. Men and women, aged 18 or older. 
2. Histologically or cytologically confirmed advanced/metastatic or surgically unresectable 
cholangiocarcinoma.  Subjects will be assigned to 1 of 3 cohorts: 
a. Cohort A:  FGFR2 translocations with a documented fusion partner in central 
laboratory report 
b. Cohort B:  other FGF/FGFR alterations. 
c. Cohort C (US only):  negative for FGF/FGFR alterations. 
3. Radiographically measurable disease per RECIST v1.1. 
4. Documentation of FGF/FGFR gene alteration status (see Appendix D). 
5. Documented disease progression after at least 1 line of prior systemic therapy. 
6. Archival tumor specimen (formalin fixed paraffin-embedded [FFPE] tumor block or 
approximately 15 slides) or willingness to undergo a pretreatment tumor biopsy to 
provide a tumor block or unstained slides.  Archival tumor biopsies are acceptable and 
should be no more than 2 years old (preferably < 1 year old and, if possible, collected 
since the completion of the last treatment); subjects with a sequencing report from the 
central genomic laboratory within approximately 2 years of screening are exempt from 
the need for tumor biopsy, but a tumor sample should be provided to the sponsor if 
available. 
7. Life expectancy ≥ 12 weeks. 
8. ECOG performance status 0 to 2 (see Table 8). 
9. Willingness to avoid pregnancy or fathering children based on the criteria below: 
a. Woman of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or 
bilateral oophorectomy OR ≥ 12 months of amenorrhea). 
b. Woman of childbearing potential who has a negative pregnancy test at screening and 
before the first dose on Day 1 and who agrees to take appropriate precautions to avoid 
pregnancy (with at least 99% certainty) from screening through safety follow-up.  
Permitted methods that are at least 99% effective in preventing pregnancy (see 
Appendix A) should be communicated to the subject and their understanding 
confirmed.  A follow-up pregnancy test will be performed at EOT visit. 
c. Man who agrees to take appropriate precautions to avoid fathering children (with at 
least 99% certainty) from screening through 90 days after last day of treatment 
(1 sperm cycle).  Permitted methods that are at least 99% effective in preventing 
pregnancy (see Appendix A) should be communicated to the subject and their 
understanding confirmed. 


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3.2. 
Subject Exclusion Criteria 
A subject who meets any of the following criteria will be excluded from the study: 
1. Prior receipt of selective FGFR inhibitor. 
2. Treatment with other investigational study drug for any indication for any reason, or 
receipt of anticancer medications within 28 days before first dose of study drug.  Subjects 
must have recovered (Grade ≤ 1 or at pretreatment baseline) from AEs from previously 
administered therapies. 
3. Untreated brain or central nervous system (CNS) metastases or brain/CNS metastases 
that have progressed (eg, evidence of new or enlarging brain metastasis or new 
neurological symptoms attributable to brain/CNS metastases).  Subjects with previously 
treated and clinically stable brain/CNS metastases and who are off all corticosteroids for 
≥ 4 weeks are eligible. 
4. Have a known additional malignancy that is progressing or requires active treatment.  
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, 
carcinoma in situ of the cervix, or other noninvasive or indolent malignancy that has 
undergone potentially curative therapy. 
5. Are pregnant or lactating. 
6. Have abnormal laboratory parameters: 
a. Total bilirubin ≥ 1.5 × upper limit of normal (ULN; ≥ 2.5 × ULN if Gilbert syndrome 
or disease involving liver). 
b. AST and ALT > 2.5 × ULN (AST and ALT > 5 × ULN in the presence of liver 
metastases). 
c. Creatinine clearance ≤ 30 mL/min based on Cockroft-Gault. 
d. Serum phosphate > institutional ULN. 
e. Serum calcium outside of the institutional normal range or serum albumin-correct 
calcium outside of the institutional normal range when serum albumin is outside of 
the institutional normal range. 
f. Potassium levels < institutional lower limit of normal; supplementation can be used to 
correct potassium level during the screening.  
7. Known history of human immunodeficiency virus (HIV) infection or positivity on 
immunoassay confirmed per local standards (NOTE:  HIV screening test is optional for 
US subjects, but subjects with known history of HIV infection will be excluded). 
8. Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. 
9. Has a history or presence of an abnormal ECG that in the investigator's opinion is 
clinically meaningful.  Subjects with a screening QTcF interval > 450 milliseconds are 
excluded. 
10. History of clinically significant or uncontrolled cardiac disease including unstable angina, 
acute myocardial infarction, New York Heart Association Class III or IV congestive heart 
failure, or arrhythmia requiring therapy.  Subjects with a pacemaker and well-controlled 
rhythm for at least 1 month prior to first dose will be allowed. 


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11. Have undergone major surgical procedure other than for diagnosis within 28 days before 
Cycle 1 Day 1. 
12. Inadequate recovery from toxicity and/or complications from a major surgery before 
starting therapy. 
13. Pregnant or nursing women or subjects expecting to conceive or father children within 
the projected duration of the study, starting with the screening visit through completion of 
safety follow-up visit (90 days from date of last dose for male subjects). 
14. Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, 
immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor 
embolization). 
15. Received prior radiation therapy administered within 4 weeks of first dose of study drug.  
Subjects must have recovered from all radiation-related toxicities, not require 
corticosteroids, and not have had radiation pneumonitis.  A 2-week washout is permitted 
for palliative radiation to non-CNS disease. 
16. History and/or current evidence of ectopic mineralization/calcification, including but not 
limited to soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph 
nodes and asymptomatic arterial or cartilage/tendon calcification. 
17. Current evidence of clinically significant corneal or retinal disorder confirmed by 
ophthalmologic examination. 
18. Current use of prohibited medication as described in Section 5.7.2. 
19. Use of any potent CYP3A4 inhibitors or inducers (Appendix B) within 14 days or 
5 half-lives (whichever is shorter) before the first dose of study drug.  Topical 
ketoconazole will be allowed. 
20. Known hypersensitivity or severe reaction to INCB054828 or excipients of INCB054828 
study drug (refer to the IB). 
21. Inability or unlikeliness to comply with the dose schedule and study evaluations, in the 
opinion of the investigator. 
22. Inability to comprehend or unwilling to sign the informed consent form (ICF). 
23. Unable or unwilling to swallow INCB054828 or significant GI disorder(s) that could 
interfere with the absorption, metabolism, or excretion. 
24. Any condition that would in the investigator's judgment interfere with full participation in 
the study, including administration of study medication and attending required study 
visits; pose a significant risk to the subject; or interfere with interpretation of study data. 
25. Subjects with history of hypovitaminosis D requiring supraphysiologic doses to replenish 
the deficiency.  Subjects receiving vitamin D food supplements are allowed. 


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4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design 
This is an open-label, monotherapy study of INCB054828 in subjects with advanced/metastatic 
or surgically unresectable cholangiocarcinoma with FGFR2 translocations, with other 
FGF/FGFR alterations, or who are negative for FGF/FGFR alterations.  The study will enroll 
approximately 140 subjects total:  100 subjects with FGFR2 translocations (Cohort A), 
20 subjects with other FGF/FGFR alterations (Cohort B), and 20 subjects with no FGF/FGFR 
alterations (Cohort C [US only]). 
Subjects will receive a once daily dose (QD) of INCB054828 at 13.5 mg on a 2-week-on therapy 
and 1-week-off therapy schedule.  Full study drug administration information can be found in 
Section 5.2. 
Subject eligibility can be based on local genomic testing results, if available.  Confirmatory 
testing through the central genomics laboratory will be performed on all subjects. 
Previous therapies may include chemotherapeutic agents, immunotherapies, with or without 
radiotherapy.  Subjects receiving radiotherapy to target lesion(s) must show progression of target 
lesion before entry into the study. 
Genomic testing results will allow subjects to be assigned to a cohort: 
• Cohort A:  FGFR2 translocations with a documented fusion partner in central 
laboratory report 
• Cohort B:  other FGF/FGFR alterations 
• Cohort C (US only):  negative for FGF/FGFR alterations 
Subjects enrolled based on a local sequencing report will be assigned to a cohort based on the 
local results.  However, final cohort assignment for statistical analysis of primary and secondary 
endpoints will be done based on the central genomics testing results. 
Treatment will start on Cycle 1 Day 1.  Subjects will undergo regular safety assessments during 
treatment as well as regular efficacy assessments.  Subjects will be allowed to continue 
administration in 21-day cycles until documented disease progression or unacceptable toxicity is 
reported.  See Figure 3 for the study design. 


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Figure 3: 
Study Design 
Advanced/metastatic/non-resectable 
cholangiocarcinoma
 FGF/FGFR status
FGFR2 translocation
Cohort A
Treatment (21-day cycle; 2-wks 
on/1 wk off)
Disease 
Assessment after 
Cycle 2
PD
SD, PR, CR
D/C tx; safety 
and survival 
follow up
Continue tx; 
assess per 
protocol
FGF/FGFR Negative
Cohort C (US subjects only)
Screen
Discontinue
Pass
SF
Other FGF/FGFR 
alterations
Cohort B
 
D/C = discontinue; SF = screen fail. 
4.2. 
Measures Taken to Avoid Bias 
This is an open-label study; no comparisons will be made between subjects or against historical 
controls.  Measurements of safety and efficacy are objective measurements, and only 
comparisons to pretreatment conditions will be made. 


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4.3. 
Number of Subjects 
4.3.1. 
Planned Number of Subjects 
Approximately 140 subjects (total) are planned for enrollment.  This may vary due to outcome of 
futility analysis. 
4.3.2. 
Replacement of Subjects 
Not applicable. 
4.4. 
Duration of Treatment and Subject Participation 
After signing the ICF, screening assessments may be completed over a period of up to 28 days.  
Each subject enrolled in the study may continue to receive study treatment in continuous 21-day 
cycles.  At the point when the subject discontinues study drug (INCB054828), the treatment 
period will end and the subject will enter the follow-up period (see Section 6.4).  Study 
participation is expected to average approximately 6 months per individual subject. 
4.5. 
Overall Study Duration 
The study begins when the first subject signs the ICF.  The end of the study will occur when all 
subjects have discontinued study drug and have completed applicable follow-up assessments. 
If there have been ≤ 2 subjects on study for more than 8 months, then a database lock of the 
study may occur to allow the analysis of the study data.  Any remaining subjects may continue to 
receive study treatment per Protocol.  The remaining subjects are considered to be on study until 
a discontinuation criterion is met and written notification is provided to the sponsor. 
4.6. 
Study Termination 
The investigator retains the right to terminate study participation at any time, according to the 
terms specified in the study contract.  The investigator is to notify the institutional review board 
(IRB)/independent ethics committee (IEC) in writing of the study's completion or early 
termination, send a copy of the notification to the sponsor or sponsor's designee, and retain 
1 copy for the site study regulatory file. 
The sponsor may terminate the study electively, if required by regulatory decision, or upon 
advice of the study committee.  If the study is terminated prematurely, the sponsor will notify the 
investigators, the IRBs and IECs, and regulatory bodies of the decision and reason for 
termination of the study. 


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5. 
TREATMENT 
5.1. 
Treatment Assignment 
5.1.1. 
Subject Numbering and Treatment Assignment 
The interactive response technology (IRT) will be contacted at the beginning of screening to 
obtain a subject number.  All subject numbers will be 6 digits; the first 3 digits will be the site 
number, and the last 3 digits will be the subject's number.  This subject number will be 
maintained throughout the study and will not be reassigned.  Subjects who withdraw consent or 
discontinue from the study after being assigned a subject number will retain their initial number. 
Site staff will contact the IRT after screening is completed to enroll the subject and to allocate 
the subject to treatment assignment and obtain the initial study drug assignment.  The 
investigator or designee will select the appropriate number of bottles of study drug from their 
stock that correspond to the dose provided by the IRT and dispense the study drug to the subject.  
All subsequent dispensing of study drug should follow this process.  Refer to the IRT manual for 
detailed information. 
If a subject is mistakenly given a bottle of study drug that is not the bottle assigned by the IRT, 
the IRT help desk must be notified immediately.  The reason for the misallocation of the study 
drug must be documented by the study site and reported to the IRB/IEC. 
For subjects who signed an ICF but are not allocated and for subjects who are allocated but were 
not treated, refer to the electronic case report form (eCRF) Completion Guidelines for instruction 
on which eCRFs to complete. 
All subjects will receive the same treatment assignment (13.5 mg QD) regardless of cohort 
assignment. 
5.1.2. 
Randomization and Blinding 
Not applicable, since this is an open-label, single-group study. 
5.2. 
Study Drug 
5.2.1. 
INCB054828 
5.2.1.1. 
Description and Administration 
INCB054828 will be self-administered as a QD oral treatment on a 21-day cycle.  Subjects will 
take study drug for 2 weeks continuously (14 days) followed by a 1-week (7 days) break.  The 
starting dose will be 13.5 mg.  Each dose of study drug should be taken immediately upon rising 
or after a 2-hour fast.  Subject should plan to fast for 1 additional hour after taking study drug. 
5.2.1.2. 
Supply, Packaging, and Labeling 
Study drug will be supplied as 2 mg and 4.5 mg tablets.  All tablet excipients comply with the 
requirements of the applicable compendial monographs (Ph Eur, USP-NF; refer to the IB).  


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INCB054828 tablets will be packaged in high-density polyethylene bottles.  No preparation is 
required. 
All Incyte investigational product labels will be in the local language and will comply with the 
legal requirements of each country. 
5.2.1.3. 
Storage 
Bottles of tablets should be stored at room temperature, 15°C to 30°C (59°F to 86°F). 
5.2.1.4. 
Instruction to Subjects for Handling Study Drug (INCB054828) 
The subject must be instructed in the handling of study drug as follows: 
• To store the study drug at room temperature. 
• To only remove from the study drug bottle the number of tablets needed at the time of 
administration. 
• Not to remove doses in advance of the next scheduled administration. 
• Tablets cannot be split or crushed 
• To make every effort to take doses on schedule. 
• To report any missed doses. 
• To take study drug immediately upon rising or after a 2-hour fast with a glass of 
water; the subject should refrain from eating 1 hour after taking study drug. 
• If the subject vomits after taking study drug, the subject should not take another dose 
that day. 
• To keep study drug in a safe place and out of reach of children. 
• To bring all used and unused study drug kits to the site at each visit. 
• If a dose of INCB054828 is missed by more than 4 hours, that dose should be skipped 
and the next scheduled dose should be administered at the usual time. 
5.3. 
Treatment Compliance 
Compliance with all study-related treatments should be emphasized to the subject by the site 
personnel, and appropriate steps should be taken to optimize compliance during the study.  
Compliance with INCB054828 will be calculated by the sponsor based on the drug 
accountability documented by the site staff and monitored by the sponsor/designee (tablet 
counts).  Subjects will be instructed to bring the study drug with them to the study visits in order 
for site personnel to conduct tablet counts to assess study drug accountability.  The drug 
accountability documentation will be used by the sponsor to calculate treatment compliance. 


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5.4. 
Treatment Interruptions and Adjustments 
5.4.1. 
Dose Modifications 
Dose interruptions and modifications may occur for individual study subjects.  The occurrence of 
toxicities (related or unrelated to study drug) will guide decisions for treatment interruptions and 
discontinuation for individual subjects.  
5.4.2. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study Drug 
Treatment with INCB054828 may be delayed up to 14 days to allow for resolution of toxicity 
(Table 3).  Subjects may resume treatment if no medical condition or other circumstance exists 
that, in the opinion of the investigator, would make the subject unsuitable for further 
participation in the study.  The treating investigator should contact the sponsor to discuss the 
case of any subject whose treatment has been delayed for more than 14 days before restarting 
treatment with INCB054828. 
Table 3: 
Guidelines for Interruption and Restarting of Study Drug 
ADVERSE EVENT 
ACTION TAKEN 
Chemistry 
• AST and/or ALT is > 5.0 × ULN. 
Note:  In subjects with liver 
metastasis-related elevations at baseline, 
contact sponsor to discuss clinical 
management and possible dose reductions. 
Step 1:  Interrupt study drug up to 2 weeks (14 days) until 
the toxicity has resolved to ≤ Grade 1 except by approval of 
the medical monitor. 
Step 2:  Restart study drug at same dose.  If assessed as 
related to study drug, restart study drug at next lower dose; 
monitor as clinically indicated. 
Other toxicities, including SRD/RPED 
• Any Grade 1 or Grade 2 toxicity. 
Continue study drug treatment and treat the toxicity; monitor 
as clinically indicated. 
• Any Grade 3 toxicity, if clinically 
significant and not manageable by 
supportive care. 
Step 1:  Interrupt study drug up to 2 weeks (14 days), until 
toxicity resolves to ≤ Grade 1. 
Step 2:  Restart study drug at same dose.  If assessed as 
related to study drug, restart study drug at next lower dose; 
monitor as clinically indicated. 
• Any recurrent Grade 3 toxicity after 
2 dose reductions. 
Discontinue study drug administration and follow-up per 
Protocol.  (Exceptions require approval of sponsor.) 
• Any other Grade 4 toxicity. 
Discontinue study drug administration and follow-up per 
Protocol. 
For subjects who present with possible or confirmed serous retinal detachment/retinal pigmented 
epithelium detachment (SRD/RPED) based on optic coherence tomography (OCT), the 
guidelines in Table 3 should be followed.  It is recommended to discuss the findings with the 
Incyte medical monitor before making changes to the subject's treatment. 


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Per CTCAE v4.03, there is a grading for retinal detachment; however, this refers to 
rhegmatogenous retinal detachment (when a hole occurs in the retina) or exudative detachment 
(fluid accumulation due to inflammatory diseases).  There is no exact CTCAE grading term for 
SRD/RPED secondary to FGFR inhibition (there is no hole in the macula, just fluid 
accumulation or detachment of retinal pigmented epithelium).  Therefore, grading should be 
based on the CTCAE term "retinopathy." 
Due to the fact subjects may enter the study with extensive pretreatment toxicities, the dose 
reduction rules are provided as guidelines (see Table 3). 
For dose adjustments, the sponsor recommends a maximum of 2 dose level reductions:  subjects 
administered 13.5 mg can decrease to 9 mg, and if additional dose reduction is required, subjects 
can decrease to 6 mg.  Dose reductions below 6 mg are not allowed.  The frequency of 
administration remains the same (once daily) and as well as the schedule (2 weeks on treatment 
followed by 1 week off treatment). 
Adverse events that have a clear alternative explanation or transient (≤ 72 hours) abnormal 
laboratory values without associated clinically significant signs or symptoms may be exempt 
from dose-reduction rules. 
5.4.3. 
Management of Hyperphosphatemia 
Hyperphosphatemia is an expected on-target pharmacologic effect of FGFR inhibition.  
Hyperphosphatemia should be managed with diet modifications, phosphate binders and diuretics, 
or a dose reduction per the recommendations in Table 4. 
Table 4: 
Recommended Approach for Hyperphosphatemia Management  
Serum Phosphate 
Level 
Supportive Care 
Guidance for 
Interruption/Discontinuation  
of INCB054828 
Guidance for 
Restarting 
INCB054828 
> 5.5 mg/dL and  
≤ 7 mg/dL 
Initiate a low-phosphate diet  
No action. 
Not applicable. 
> 7 mg/dL and 
≤ 10 mg/dL  
Initiate/continue a low-
phosphate diet and initiate 
phosphate-binding therapy once 
serum phosphate level is 
> 7 mg/dL.  Monitor serum 
phosphate at least twice a week 
and adjust the dose of binders as 
needed; continue to monitor 
serum phosphate at least twice a 
week until return to ≤ 7 mg/dL. 
If serum phosphate level 
continues to be > 7 mg/dL and 
≤ 10 mg/dL with concomitant 
phosphate-binding therapy for 
2 weeks, or if there is recurrence 
of serum phosphate level in this 
range, interrupt INCB054828 for 
up to 2 weeks (not including the 
planned dose interruption per 
treatment cycle). 
Restart at the same 
dose when serum 
phosphate is 
≤ 7 mg/dL.  If serum 
phosphate level 
recurs at > 7 mg/dL, 
restart study drug 
with dose reduction. 
> 10 mg/dL 
Continue to maintain a 
low-phosphate diet, adjust 
phosphate-binding therapy, and 
start/continue phosphaturic 
agent.  Continue to monitor 
serum phosphate at least twice a 
week until return to ≤ 7 mg/dL. 
If serum phosphate level is 
> 10 mg/dL for 1 week following 
phosphate-binding therapy and 
low phosphate diet, interrupt 
study drug.  If there is recurrence 
of serum phosphate level in this 
range following 2 dose 
reductions, permanently 
discontinue INCB054828. 
Restart study drug at 
reduced dose with 
phosphate binders 
when serum 
phosphate is 
≤ 7 mg/dL. 


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5.4.4. 
Criteria for Permanent Discontinuation of Study Drug 
The occurrence of unacceptable toxicity not caused by the underlying malignancy will be 
presumed to be related to study drug treatment and will require that the study drug be 
permanently discontinued.  Unacceptable toxicity is defined as follows: 
• Occurrence of an AE that is related to treatment with the study drug that, in the 
judgment of the investigator or the sponsor's medical monitor, compromises the 
subject's ability to continue study-specific procedures or is considered to not be in the 
subject's best interest. 
• An AE requiring more than 2 dose reductions. 
• Persistent AE requiring a delay of therapy for more than 21 days unless a greater 
delay has been approved by the sponsor. 
• Increase in QT/QTcF to > 500 milliseconds or to > 60 milliseconds over baseline.  In 
case of a QTc > 500 milliseconds, the subject must be hospitalized and a continuous 
ECG monitoring must be set up until the measure of the QTc interval decreases below 
500 milliseconds and until acceptable in the opinion of a local cardiologist. 
5.5. 
Withdrawal of Subjects From Study Treatment 
5.5.1. 
Withdrawal Criteria 
Subjects must be withdrawn from study treatment for the following reasons: 
• The subject becomes pregnant. 
• Consent is withdrawn.  Note  Subjects may choose to discontinue study treatment and 
remain in the study to be followed for progression and survival. 
• Further treatment would be injurious to the subject's health or well-being, in the 
investigator's medical judgment.  Subject would still be followed for progression and 
survival. 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority, IRB, or IEC. 
• Unacceptable toxicity has occurred. 
• Disease progression has been reported. 
• Other antineoplastic treatment is initiated. 
A subject may be discontinued from study treatment as follows: 
• If, during the course of the study, a subject is found not to have met eligibility criteria 
but is receiving clinical benefit as per the investigator, the medical monitor, in 
collaboration with the investigator, will determine whether the subject should be 
withdrawn from the study.  This includes cases where the local genomic testing result 
is positive for an FGF/FGFR alteration but the central genomic testing is not. 
• If a subject is noncompliant with study procedures or study drug administration in the 
investigator's opinion, the sponsor should be consulted for instruction on handling the 
subject. 


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5.5.2. 
Withdrawal Procedures 
In the event that the decision is made to permanently discontinue the study drug, the subject will 
be withdrawn from the study and the end-of-treatment visit should be conducted.  Reasonable 
efforts should be made to have the subject return for a follow-up visit.  These visits are described 
in Section 6.  The last date of the last dose of study drug and the reason for subject withdrawal 
will be recorded in the eCRF. 
5.6. 
Withdrawal of Subjects From Study 
If the subject discontinues study treatment and actively withdraws consent for collection of 
follow-up data (safety follow-up or disease assessment), then no additional data collection 
should occur; however, subjects will have the option of withdrawing consent for study treatment 
but continuing in the follow-up period of the study for safety/efficacy assessments. 
5.7. 
Concomitant Medications 
5.7.1. 
Restricted Medications 
The use of mild or moderate CYP3A4 inhibitors and OCT2 substrates, such as metformin, 
should involve careful monitoring in relation to safety. 
Calcium-based phosphate binding medications should not be used due to a concern for soft tissue 
mineralization. 
5.7.2. 
Prohibited Medications 
The following medications and measures are prohibited: 
• The concomitant administration of potent CYP3A4 inhibitors and inducers and 
moderate CYP3A4 inducers.  Based on the low overall bioavailability of topical 
ketoconazole, there are no restrictions on topical ketoconazole.  See Appendix B for a 
list of potent CYP3A4 inhibitors and inducers. 
• Any concomitant use of a selective FGFR inhibitor (other than the study drug) 
• Investigational study drug for any indication. 
• Use of any anticancer medications other than the study medication. 
6. 
STUDY ASSESSMENTS 
All study assessments will be performed as indicated in the schedule of assessments (Table 5), 
and all laboratory assessments will be performed as indicated in Table 6. 
Table 7 presents a summary of clinical laboratory analytes to be assessed.  The order of 
assessments is suggested by the order of mention within the schedule.  See Section 7 for 
instructions on each assessment.  Further details of study procedures and assessments can be 
found in the study reference manual. 


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Table 5: 
Study Assessments 
Procedure 
Protocol 
Section 
Pre-
screening 
Screening 
Treatment 
EOT 
Follow-Up 
Notes 
Cycle 1 
Cycle 2+ 
Days 
-28 to -1 
Day 1 
Day 8  
(± 3 
days) 
Day 15  
(± 3 
days) 
Day 1  
(± 3 
days) 
Safety 
Disease 
Status 
Survival 
EOT + 30 
(+5) days 
Every 
9 weeks 
Every 
12 weeks 
 Genomic testing 
7.1  
X 
X* 
 
 
 
 
 
 
 
 
* May be done during 
prescreening or during 
screening. 
Informed consent 
7.1  
X 
X 
 
 
 
 
 
 
 
 
 
Eye examination 
(includes slit lamp, 
visual acuity, 
fundoscopy with 
digital imaging, 
and OCT 
7.5.5  
 
X 
 
 
 
X* 
X 
 
 
 
* Eye examination to be 
performed every 3 cycles 
(± 14 days) starting with 
Cycle 3 and/or as 
clinically indicated. 
Review inclusion 
and exclusion 
criteria 
3 
 
X 
X 
 
 
 
 
 
 
 
 
Demography and 
medical history 
7.3 
 
X 
 
 
 
 
 
 
 
 
 
Prior/concomitant 
medications 
7.4 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Physical 
examination/ body 
weight, height 
7.5.2  
 
X* 
X 
X 
X 
X 
X 
X 
 
 
* Comprehensive 
examination at screening, 
targeted physical 
examination thereafter. 
Vital signs 
7.5.3  
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
12-lead ECG 
7.5.4  
 
X 
X 
 
X 
X 
X 
X 
 
 
 
ECOG status 
7.6.2  
 
X 
X 
X 
X 
X 
X 
X 
 
 
 


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Table 5: 
Study Assessments (Continued) 
Procedure 
Protocol 
Section 
Pre-
Screening 
Screening 
Treatment 
EOT 
Follow-Up 
Notes 
Cycle 1 
Cycle 2+ 
Days 
-28 to -1 
Day 1 
Day 8  
(± 3 
days) 
Day 15  
(± 3 
days) 
Day 1  
(± 3 
days) 
Safety 
Disease 
Status 
Survival 
EOT + 30 
(+5) days 
Every 
9 weeks 
Every 
12 weeks 
CT or MRI 
7.6.1  
 
X 
 
 
 
X* 
X 
 
X** 
 
* Every 2 cycles through 
Cycle 4; every 3 cycles 
thereafter starting with 
Cycle 7. 
** Subjects who 
discontinue study 
treatment for a reason 
other than disease 
progression. 
Review AEs 
7.5.1  
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Survival status 
7.8.2  
 
 
 
 
 
 
 
 
 
X* 
* Once a subject has 
received the last dose of 
study drug, confirmed 
disease progression, or 
starts a new anticancer 
therapy. 
CT = computed tomography; MRI = magnetic resonance imaging. 


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Table 6: 
Laboratory Assessments 
 
Protocol 
Section 
Prescreening 
Screening 
Treatment 
EOT 
Follow-
Up 
Notes 
Cycle 1 
Cycles 2+ 
Day 1 
Day 8  
(± 3 Days) 
Day 15  
(± 3 Days) 
Serum chemistries 
7.5.6  
 
X 
X* 
X 
X 
X 
X 
X 
* May be performed within 3 days of 
the first dose. 
Hematology 
7.5.6  
 
X 
X* 
X 
X 
X 
X 
X 
* May be performed within 3 days of 
the first dose. 
Lipid panel 
7.5.6  
 
 
X 
 
 
 
X 
 
 
Endocrine 
7.5.6  
 
X 
X 
 
 
X 
X 
 
 
Coagulation panel 
7.5.6  
 
X 
 
 
 
X* 
X 
 
* Only every 3 cycles starting at 
Cycle 3. 
Hepatitis screening 
7.5.6.2  
 
X 
 
 
 
 
 
 
 
Urinalysis 
7.5.6  
 
X 
 
 
 
X* 
 
 
* Only every 3 cycles starting at 
Cycle 3. 
Pregnancy test 
7.5.6.1  
 
X* 
X** 
 
 
X** 
X** 
 
*  Serum 
** Day 1 of each cycle; urine 
pregnancy test allowed. 
HIV testing 
7.5.6.3  
 
X* 
 
 
 
 
 
 
* Optional for US subjects. 
Central laboratory 
Blood sample for 
PK 
7.7 
 
 
 
X* 
 
 
 
 
Samples will be drawn at predose, 
1-2 hours postdose, and 4-12 hours 
postdose (3 samples total). 
*Subject must fast 8 hours before 
first sample (predose). 
Tumor tissue 
sampling/archival 
tissue 
7.8  
X* 
 
 
 
 
X** 
 
 
* Slides or FFPE block must be 
provided. 
** Optional on-treatment or EOT 
biopsy, such as disease progression 
after complete or PR. 


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Table 7: 
Laboratory Tests:  Required Analytes 
Serum Chemistries 
Hematology 
Urinalysis With 
Microscopic Examination 
Hepatitis Screening 
Coagulation 
Albumin 
Alkaline phosphatase 
ALT 
AST  
Bicarbonate (not in Japan) 
Blood urea nitrogen or urea 
Calcium 
Chloride  
Creatinine 
Glucose 
Lactate dehydrogenase 
Phosphate 
Potassium 
Sodium 
Total bilirubin 
Direct bilirubin (if total bilirubin is 
elevated above ULN) 
Total protein 
Uric acid 
Vitamin D (25-hydroxyvitamin D 
and 1,25-dihidrosyvitamin D) 
Complete blood count, 
including: 
Hemoglobin 
Hematocrit 
Platelet count 
Red blood cell count 
White blood cell count 
 
Differential count, including: 
Basophils 
Eosinophils 
Lymphocytes 
Monocytes 
Neutrophils 
 
Absolute values must be 
provided for:  
WBC differential laboratory 
results: 
Lymphocytes 
Neutrophils 
 
Color and appearance 
pH and specific gravity 
Bilirubin 
Glucose 
Ketones 
Leukocytes 
Nitrite 
Occult blood 
Protein 
Urobilinogen 
Hepatitis B surface antigen 
Hepatitis B surface antibody 
Hepatitis B core antibody 
HCV antibody 
NOTE:  If any of the above 
are positive, HBV-DNA, 
HCV-RNA to assess risk of 
reactivation. 
PT 
PTT or aPTT 
INR 
Lipid Panel 
Other 
Pregnancy Testing 
Total cholesterol 
Triglycerides 
LDL 
HDL 
Endocrine- parathyroid 
hormone 
HIV testing (optional for US 
subjects) 
Female subjects of 
childbearing potential 
only require a serum test 
at screening and a urine 
pregnancy test before the 
first dose on Day 1 of 
every cycle before dose 
administration and at 
EOT. 
Pregnancy tests (serum or 
urine) should be repeated 
if required by local 
regulations. 
HDL = high-density lipoprotein; INR = international normalized ratio; LDL = low-density lipoprotein; PT = prothrombin time; PTT = partial thromboplastin time; WBC = white 
blood cell. 
Note:  Additional tests may be required, as agreed by investigator and sponsor, based on emerging safety data.


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6.1. 
Prescreening and Screening 
Prescreening is available for subjects without a genomic testing report (results within 
approximately 2 years of screening are valid for this study).  Prescreening allows genomic 
testing to be performed outside of the 28-day screening window. 
Screening is the interval between signing the ICF and the day that the subject is enrolled in the 
study (Cycle 1 Day 1).  Screening may not exceed 28 days.  Assessments that are required to 
demonstrate eligibility may be performed over the course of 1 or more days during the screening 
process. 
Procedures conducted as part of the subject's routine clinical management (eg, blood count, 
imaging study) and obtained before signing of informed consent may be used for screening or 
baseline purposes provided that the procedure meets the Protocol-defined criteria and has been 
performed in the time frame of the study (ie, within 28 days of Cycle 1 Day 1).  All information 
associated with eligibility requirements must be entered into the appropriate eCRF pages. 
Results from the screening visit evaluations will be reviewed to confirm subject eligibility before 
enrollment or the administration of study drug.  Tests with results that fail eligibility 
requirements may be repeated once during screening if the investigator believes the results to be 
in error.  For screening assessments that are repeated, the most recent available result before 
treatment assignment will be used to determine subject eligibility.  Treatment should start as 
soon as possible, but within 3 days after the date of enrollment.  Additionally, a subject who fails 
screening may repeat the screening process 1 time if the investigator believes that there has been 
a change in eligibility status (eg, after recovery from an infection).  Subjects who are rescreened 
will receive a new subject number through the IRT. 
6.2. 
Treatment 
The treatment period begins on the day that the subject receives the first dose of study drug 
(Cycle 1 Day 1) through the point at which the investigator determines that the subject will be 
permanently discontinued from study drug.  Cycle 1 Day 1 must be no more than 28 days after 
the subject has signed the ICF and no more than 3 days after the date of enrollment.  Dates for 
subsequent study visits will be determined based on this day and should occur within 3 days (+/-) 
of the scheduled date unless delayed for safety reasons.  At Cycle 1 Day 1, results from 
screening visit evaluations should be reviewed to determine whether the subject continues to 
meet the eligibility requirements, as specified in the Protocol. 
6.3. 
End of Treatment 
When the subject permanently discontinues study drug, the EOT visit should be conducted.  If 
the EOT visit coincides with a regular study visit, then the EOT evaluations will supersede those 
of that scheduled visit, and the data should be entered in the EOT visit in the eCRF.  The subject 
should be encouraged to return for the follow-up visit. 


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6.4. 
Follow-Up 
6.4.1. 
Safety Follow-Up 
The safety follow-up period is the interval between the EOT visit and the scheduled follow-up 
visit, which should occur 30 to 35 days after the EOT visit (or after the last dose of study drug if 
the EOT visit was not performed).  Adverse events and SAEs must be reported up until at least 
30 days after the last dose of study drug, the date of the follow-up visit, or until toxicities 
resolve, return to baseline, or are deemed irreversible, whichever is longer.  Reasonable efforts 
should be made to have the subject return for the follow-up visit and report any AEs that may 
occur during this period. 
If a subject is scheduled to begin a new anticancer therapy before the end of the 30-day safety 
follow-up period, then the safety follow-up visit should be performed before new anticancer 
therapy is started.  Once new anticancer therapy has been initiated, the subject will move into the 
survival follow-up period. 
6.4.2. 
Disease Status Follow-Up 
Subjects who discontinue study treatment for a reason other than disease progression will move 
into the disease status follow-up period and should be assessed every 9 weeks by radiologic 
imaging to monitor disease status.  Every effort should be made to collect information regarding 
disease status until: 
• The start of new antineoplastic therapy. 
• Disease progression. 
• Death. 
• The end of the study. 
6.4.3. 
Survival Follow-Up 
Once a subject has received the last dose of study drug, confirmed disease progression, or starts a 
new anticancer therapy, the subject moves into the survival follow-up period and should be 
contacted by telephone, email, or visit at least every 12 weeks to assess for survival status until 
death, withdrawal of consent, or the end of the study, whichever occurs first. 
6.5. 
End of Study 
The end of the study may be designated as the timepoint when all subjects have discontinued the 
study or the sponsor terminates the study. 
6.6. 
Unscheduled Visits 
Unscheduled visits may occur at any time as medically warranted.  Any assessments performed 
during those visits should be recorded in the eCRF. 


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7. 
CONDUCT OF STUDY ASSESSMENTS AND PROCEDURES 
7.1. 
Administration of Informed Consent Form 
A valid informed consent must be obtained from the study subject before any study-specific 
procedures are conducted using an ICF approved by the local IRB/IEC that contains all elements 
required by ICH E6 and describes the nature, scope, and possible consequences of the study in a 
form understandable to the study subject.  Local and institutional guidelines for ICF content and 
administration must be followed; the original signed ICF must be retained by the investigator, 
and a copy of the signed ICF must be provided to the study subject.  The informed consent 
process for each subject must be documented in writing within the subject source documentation. 
7.2. 
Interactive Response Technology Procedure 
The IRT will be contacted to obtain a subject ID number when a subject enters screening.  Upon 
determining that the subject is eligible for study entry, the IRT will be contacted to obtain the 
treatment assignment.  Additionally, the IRT will be contacted at each regular study visit to 
update the study drug supply.  See appropriate information in Section 5.1.1. 
7.3. 
Demography and Medical History 
7.3.1. 
Demographics and General Medical History 
Demographic data and general medical history will be collected at screening. 
7.3.2. 
Disease Characteristics and Treatment History 
A disease-targeted medical and medication history will be collected at screening. 
7.4. 
Prior and Concomitant Medications and Procedures 
Prior and concomitant medications and procedures will be reviewed to determine subject 
eligibility.  All concomitant medications and measures must be recorded in the eCRF, and any 
medication received or procedure performed within 28 days before first dose and up to the end of 
study will be recorded in the eCRF.  The medication record will be maintained after signing the 
ICF to document concomitant medications, including any changes to the dose or regimen.  
Concomitant medications include any prescription, over-the-counter, or natural/herbal 
preparations taken or administered during the study period.  Concomitant treatments and/or 
procedures that are required to manage a subject's medical condition during the study will also be 
recorded in the eCRF. 
7.5. 
Safety Assessments 
7.5.1. 
Adverse Events 
Adverse events will be monitored from the time the subject signs the ICF.  Subjects will be 
instructed to report all AEs during the study and will be assessed for the occurrence of AEs 
throughout the study.  In order to avoid bias in eliciting AEs, subjects will be asked general, 


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nonleading questions such as "How are you feeling?"  All AEs (serious and nonserious) must be 
recorded on the source documents and eCRFs regardless of the assumption of a causal 
relationship with the study drug.  The definition, reporting, and recording requirements for AEs 
are described in Section 8. 
7.5.2. 
Physical Examinations 
Clinically notable abnormalities that are considered clinically significant in the judgment of the 
investigator are to be reported as AEs. 
Physical examinations must be performed by a medically qualified individual such as a licensed 
physician, physician's assistant, or an advanced registered nurse practitioner, as local law 
permits. 
Clinically notable abnormalities that are considered clinically significant in the judgement of the 
investigator are to be reported as AEs. 
7.5.2.1. 
Comprehensive Physical Examination 
The comprehensive physical examination will include height (at screening) and body weight and 
assessment(s) of the following organ or body systems:  skin; head, eyes, ears, nose, and throat; 
thyroid; lungs; cardiovascular system; abdomen (liver, spleen); extremities; and lymph nodes, as 
well as a brief neurological examination. 
7.5.2.2. 
Targeted Physical Examination 
The targeted physical examination will be a symptom-directed evaluation.  The targeted physical 
examination will include body weight and assessment(s) of the body systems or organs, as 
indicated by subject symptoms, AEs, or other findings.   
7.5.3. 
Vital Signs 
Vital sign measurements include blood pressure, pulse, respiratory rate, and body temperature.  
Blood pressure and pulse will be taken with the subject in the recumbent, semirecumbent, or 
sitting position after approximately 5 minutes of rest.  Clinically notable abnormalities that are 
considered clinically significant in the judgment of the investigator are to be reported as AEs. 
7.5.4. 
Electrocardiograms 
All 12-lead ECGs will be performed with the subject in a recumbent or semirecumbent position 
after 5 minutes of rest. 
The 12-lead ECGs will be interpreted by the investigator at the site to be used for immediate 
subject management.  The decision to include or exclude a subject or withdraw a subject from 
the study based on an ECG flagged as "Abnormal, Clinically Significant" is the responsibility of 
the investigator, in consultation with the sponsor's medical monitor, as appropriate.  Clinically 
notable abnormalities that are considered clinically significant in the judgment of the investigator 
are to be reported as AEs. 


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7.5.5. 
Comprehensive Eye Examination 
A comprehensive eye examination should be performed by a qualified ophthalmologist at 
screening, once every 3 cycles (± 14 days, starting at Cycle 3), at EOT, and as clinically 
indicated.  The eye examination should include a visual acuity test, slit-lamp examination, 
funduscopy with digital imaging, and OCT.  Every effort should be made to ensure that all 
subsequent examinations are performed by the same ophthalmologist. 
7.5.6. 
Laboratory Assessments 
Each site's local laboratory will be used for eligibility and ongoing safety assessments.  
Chemistry, hematology, coagulation panel, lipid panel, serology, endocrine function, and 
urinalysis will all be analyzed by each site's laboratory. 
7.5.6.1. 
Pregnancy Testing 
A serum pregnancy test will be required for all women of childbearing potential during 
screening.  A urine pregnancy test is allowed on Day 1 (before the first dose of study drug), 
Day 1 of each subsequent cycle, and at the EOT visit.  Urine pregnancy tests will be conducted 
as outlined in Table 6, as medically indicated, or per country-specific requirement.  Urine 
pregnancy tests will be performed locally.  If a urine pregnancy test is positive, the results should 
be confirmed with a serum pregnancy test. 
If the serum pregnancy test is negative after a urine test was positive, then the investigator will 
assess the potential benefit/risk to the subject and determine whether it is in the subject's best 
interest to resume study drug and continue participation in the study. 
7.5.6.2. 
Hepatitis Screening Tests 
Subjects will undergo screening for hepatitis B or C through their local laboratory.  If the results 
are positive, then subjects will be required to undergo additional testing.  Subjects with chronic 
or cleared hepatitis B or C will be allowed to enroll.  Chronic is defined as subjects with no 
evidence of liver cirrhosis or active hepatitis (elevation of transaminases) but with positive 
anti-HCV antibody test or positive HCV RNA, positive HBV surface antigen, or positive HBV 
DNA. 
7.5.6.3. 
HIV Screening Tests 
Subjects outside of the US will be required to submit to an HIV test during screening to ensure 
negative HIV status before enrollment/Cycle 1 Day 1.  This test is optional for US subjects. 
7.5.6.4. 
Evaluation of FGF and FGFR Genetic Alterations 
All potential subjects must be evaluated for FGF/FGFR alteration status before enrollment.  
Subject eligibility can be based on local genomic testing results, if available.  Confirmatory 
testing through the central genomics laboratory will be performed on all subjects.  See  
Appendix D for a list of alterations. 


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7.6. 
Efficacy Assessments 
7.6.1. 
Tumor Imaging 
Objective assessment of tumor status is required using appropriate disease-specific techniques, 
and a central radiologic facility will be used to determine responses and will be logged in to the 
eCRF.  RECIST v1.1 (Eisenhauer et al 2009) will be used, and the recommended method for 
measuring and following tumor burden will be CT scan, to include the thorax, abdomen, and 
pelvis; the neck can be included if needed.  Alternative modalities (eg, MRI) may be substituted 
for a CT scan at the discretion of the investigator, provided that the same modality is used 
throughout the study and that the methodology is consistent with RECIST v1.1. 
The schedule for efficacy assessments will be at screening (this will be considered the baseline 
scan), every 2 cycles (every 6 weeks) for the first 4 cycles, every 3 cycles (every 9 weeks) 
thereafter, and then at EOT (if applicable).  For subjects who discontinue treatment for reasons 
other than disease progression, every effort should be made to continue monitoring their disease 
status by radiographic imaging until 1) start of new anticancer therapy, 2) documented disease 
progression, 3) death, or 4) end of study, whichever occurs first. 
7.6.2. 
Eastern Cooperative Oncology Group Performance Status 
Eastern Cooperative Oncology Group performance status (Table 8) will be assessed at the visits 
specified in the schedule of assessments (Table 5). 
Table 8: 
ECOG Performance Status 
Grade 
Performance Status 
0 
Fully active, able to carry on all predisease 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. 
Source:  Oken et al 1982. 
 
 
 
 
 
7.6.4. 
Survival Follow-Up 
For subjects having entered the survival follow-up period of the study, the site will use 
continuing subject records to supply data on subsequent treatment regimens, tumor assessments 


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(if discontinued treatment for a reason other than progression), and OS in the eCRF.  For subjects 
who do not intend to return to the study investigator for their ongoing care, follow-up should be 
maintained by phone contact, patient records, and public records/databases at intervals of no 
longer than 12 weeks.  After the final primary analysis is performed, the follow-up interval for 
subsequent anticancer treatments and survival may be reduced to every 12 weeks (see 
Section 6.4). 
7.7. 
Pharmacokinetic Assessments 
7.7.1. 
Blood Sample Collection 
Pharmacokinetic samples will be obtained on Cycle 1, Day 8 at predose, 1 to 2 hours postdose, 
and 4 to 12 hours postdose (3 samples total; Table 6).  The exact date and time of the PK blood 
draws will be recorded in the eCRF along with the date and time of the last dose of study drug 
preceding the blood draw and the time of the most recent meal.  Instructions for sample 
preparation and shipping to the central laboratory will be provided in the Laboratory Manual.  
The subject will receive a reminder card in advance of the study visit, providing instruction to 
hold the dose of study drug on the day of the visit, a place to record the time of the previous dose 
of study drug, and a place to record the time of the most recent meal or snack consumed. 
On Cycle 1 Day 8, it is important to note that the subject must refrain from eating 8 hours prior 
to arriving at the site.  The initial predose sample should be drawn approximately 1 hour before 
study drug administration.  Subjects then need to fast for 1 additional hour after taking study 
medication.  Once the subject takes the study drug, any subsequent timed samples will be taken. 


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8. 
SAFETY MONITORING AND REPORTING 
8.1. 
Adverse Events 
8.1.1. 
Definitions 
For the purposes of this Protocol, an adverse event (AE) is defined as any untoward medical 
occurrence associated with the use of a drug in humans, whether or not considered drug related, 
that occurs after a subject provides informed consent.  Abnormal laboratory values or test results 
occurring after informed consent constitute AEs only if they induce clinical signs or symptoms, 
are considered clinically meaningful, require therapy (eg, hematologic abnormality that requires 
transfusion), or require changes in the study drug(s). 
8.1.2. 
Reporting 
Adverse events that begin or worsen after informed consent should be recorded on the Adverse 
Events form of the eCRF.  Conditions that were already present at the time of informed consent 
should be recorded on the Medical History form in the eCRF.  Monitoring for the occurrence of 
new AEs should be continued for at least 30 days after the last dose of study drug.  Adverse 
events (including laboratory abnormalities that constitute AEs) should be described using a 
diagnosis whenever possible rather than by individual underlying signs and symptoms.  When a 
clear diagnosis cannot be identified, each sign or symptom should be reported as a separate AE. 
The term "disease progression" should be recorded as an AE/SAE only if there are no other 
identifiable AEs/SAEs associated with the disease progression at the time of reporting.  For 
events associated with disease progression, the relevant signs and symptoms should be reported 
using a diagnosis whenever possible rather than individual underlying signs and symptoms.  


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When a clear diagnosis cannot be identified, each sign or symptom should be reported as a 
separate AE.  If the events resulting from disease progression meet the criteria for an SAE (eg, 
resulted in hospitalization, a life-threatening event, or death), the specific event(s) should be 
reported as an SAE(s) as described in Section 8.3.2.  In both cases (ie, AEs or SAEs related to 
disease progression), it should be indicated that each event (reported as a diagnosis or as signs 
and symptoms) is related to disease progression on the Adverse Events form of the eCRF. 
The severity of AEs will be assessed using CTCAE v4.03 Grades 1 through 4.  The CTCAE 
v4.03 severity of Grade 5 will not be used; AEs resulting in death will be graded accordingly 
using Grades 1 through 4 and have the outcome noted as fatal.  If an event is not classified by 
CTCAE, the severity of the AE will be graded according to the scale below to estimate the grade 
of severity: 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
Grade 2 
Moderate; minimal, local, or noninvasive intervention indicated; limiting 
age-appropriate activities of daily living. 
Grade 3 
Severe or medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self-care activities of 
daily living. 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Note that a grading scale for hyperphosphatemia (elevated serum phosphate) is not included in 
CTCAE v 4.03.  Grading should be applied using the table above ("investigations-other, specify" 
category in CTCAE v 4.03).  Hyperphosphatemia should be graded based on clinical severity 
(eg, symptoms) and medical intervention measures taken (eg, phosphate binders) and not on 
phosphate levels. 
The occurrence of AEs should be sought by nondirective questioning of the subject during the 
screening process after signing the ICF and at each visit during the study.  Adverse events may 
also be detected when they are volunteered by the subject during the screening process or 
between visits, or through physical examination, laboratory test, or other assessments.  To the 
extent possible, each AE should be evaluated to determine: 
• The severity grade (CTCAE Grade 1 to 4). 
• Whether there is at least a reasonable possibility that the AE is related to the study 
treatment:  suspected (yes) or not suspected (no). 
• The start and end dates, unless unresolved at final follow-up. 
• The action taken with regard to study drug. 
• The event outcome (eg, not recovered/not resolved, recovered/resolved, 
recovering/resolving, recovered/resolved with sequelae, fatal, unknown). 
• The seriousness, as per serious adverse event (SAE) definition provided in 
Section 8.3.1. 
Unlike routine safety assessments, SAEs are monitored continuously and have special reporting 
requirements (see Section 8.3.2). 


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All AEs should be treated appropriately.  If an AE is treated with a concomitant medication or 
nondrug therapy, this action should be recorded on Adverse Event form and the treatment should 
be specified on the Prior/Concomitant Medications or Procedures and Non-Drug Therapy form 
in the eCRF. 
Once an AE is detected, it should be followed until it has resolved or until it is judged to be 
permanent; assessment should be made at each visit (or more frequently if necessary) of any 
changes in severity, the suspected relationship to the study drug, the interventions required to 
treat the event, and the outcome. 
When the severity of an AE changes over time for a reporting period (eg, between visits), each 
change in severity will be reported as a separate AE until the event resolves.  For example, 
2 separate AEs will be reported if a subject has Grade 1 diarrhea, meeting the definition of an 
AE, that lasts for 3 days before worsening to a Grade 3 severity.  The Grade 1 event will be 
reported as an AE with a start date equal to the day the event met the Grade 1 AE definition and 
a stop date equal to the day that the event increased in severity from Grade 1 to Grade 3.  The 
Grade 3 event will also be reported as an AE, with the start date equal to the day the event 
changed in intensity from Grade 1 to Grade 3 and a stop date equal to the day that the event 
either changed severity again or resolved. 
8.2. 
Laboratory Test Abnormalities 
Laboratory abnormalities that constitute an AE in their own right (considered clinically 
meaningful, induce clinical signs or symptoms, require concomitant therapy, or require changes 
in study drug) should be recorded on the Adverse Event form in the eCRF.  Whenever possible, a 
diagnosis rather than a symptom should be provided (eg, "anemia" instead of "low hemoglobin").  
Laboratory abnormalities that meet the criteria for AEs should be followed until they have 
returned to normal or an adequate explanation of the abnormality is found.  When an abnormal 
laboratory test result corresponds to a sign or symptom of a previously reported AE, it is not 
necessary to separately record the laboratory test result as an additional event. 
Laboratory abnormalities that do not meet the definition of an AE should not be reported as AEs.  
A Grade 3 or 4 (severe) AE does not automatically indicate an SAE unless it meets the definition 
of serious, as defined in Section 8.3.1.  A dose modification for the laboratory abnormality may 
be required (see Section 5.4) and should not contribute to the designation of a laboratory test 
abnormality as an SAE. 
8.3. 
Serious Adverse Events 
8.3.1. 
Definitions 
An SAE is defined as an event that meets at least 1 of the following criteria: 
• Is fatal or life-threatening. 
• Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is a result of: 
− A routine treatment or monitoring of the studied indication not associated with 
any deterioration in condition.   


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− An elective surgery or preplanned treatment for a pre-existing condition that is 
unrelated to the indication under study and has not worsened since signing the 
ICF. 
− A treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE and not resulting in hospital admission. 
− Any social reasons and respite care, in the absence of any deterioration in the 
subject's general condition. 
• Results in persistent or significant disability, incapacity, or a substantial disruption of 
a person's ability to conduct normal life functions. 
• Constitutes a congenital anomaly or birth defect. 
• Is considered to be an important medical event or a medically significant event that 
may not result in death, be immediately life-threatening, or require hospitalization but 
may be considered serious when, based on appropriate medical judgment, the event 
may jeopardize the subject or may require medical or surgical intervention to prevent 
1 of the outcomes listed above. 
8.3.2. 
Reporting 
Every SAE, regardless of suspected causality (eg, relationship to study drug(s) or study 
procedure or disease progression), occurring after the subject has signed the ICF through the last 
study visit (or 30 days after the last dose of study drug, whichever is later) must be reported to 
the sponsor (or designee) within 24 hours of learning of its occurrence, unless otherwise 
specified by the Protocol.  Any SAEs occurring more than 30 days after the last dose of study 
drug should be reported to the sponsor or its designee only if the investigator suspects a causal 
relationship to the study drug. 
Information about all SAEs is collected and recorded on the Adverse Event form of the eCRF.  
The investigator must assess and record the causal relationship of each SAE to the study 
treatment.   
The investigator must also complete the Incyte Serious Adverse Event Report Form, in English, 
and send the completed and signed form to the sponsor or designee within 24 hours of becoming 
aware of the SAE.  The investigator must provide a causality assessment, that is, assess whether 
there is at least a reasonable possibility that the SAE is related to the study treatment:  suspected 
(yes) or not suspected (no).  Refer to the Incyte Reference Guide for Completing the Serious 
Adverse Event Report Form. 
The contact information of the sponsor's study-specific representatives is listed in the 
investigator manual provided to each site.  The original copy of the SAE Report Form and the 
confirmation sheet must be kept at the study site. 
Investigational site personnel must report any new information regarding the SAE within 
24 hours of becoming aware of the information in the same manner that the initial SAE Report 
Form was sent.  Follow-up information is recorded on an amended or new SAE Report Form, 
with an indication that it is follow-up to the previously reported SAE and the date of the original 
report.  The follow-up report should include information that was not provided on the previous 


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SAE Report Form, such as the outcome of the event (eg, resolved or ongoing), treatment 
provided, action taken with study drug because of the SAE (eg, dose reduced, interrupted, or 
discontinued), or subject disposition (eg, continued or withdrew from study participation).  Each 
recurrence, complication, or progression of the original event should be reported as follow-up to 
that event, regardless of when it occurs. 
If the SAE is not documented in the IB for the study drug (new occurrence) and is thought to be 
related to the sponsor's study drug, the sponsor or its designee may urgently require further 
information from the investigator for reporting to health authorities.  The sponsor or its designee 
may need to issue an Investigator Notification (IN) to inform all investigators involved in any 
study with the same drug that this SAE has been reported.  Suspected Unexpected Serious 
Adverse Reactions (SUSARs) will be collected and reported to the competent authorities and 
relevant ethics committees in accordance with Directive 2001/20/EC, or as per national 
regulatory requirements in participating countries. 
8.4. 
Emergency Unblinding of Treatment Assignment 
Not applicable. 
8.5. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE unless there is suspicion that study drug may 
have interfered with the effectiveness of a contraceptive medication or method.  When a 
pregnancy has been confirmed in a subject during maternal or paternal exposure to study drug, 
the following procedures should be followed in order to ensure subject safety: 
• The study drug must be discontinued immediately (female subjects only; see 
Section 5.4.2 for the maximum permitted duration of study drug interruption). 
• The investigator must complete and submit the Incyte Clinical Trial Pregnancy form 
to the sponsor or its designee within 24 hours of learning of the pregnancy. 
Data on fetal outcome and breastfeeding are collected for regulatory reporting and drug safety 
evaluation.  Follow-up should be conducted for each pregnancy to determine outcome, including 
spontaneous or voluntary termination, details of the birth, and the presence or absence of any 
birth defects, congenital abnormalities, or maternal and/or newborn complications, by following 
until the first well-baby visit.  Pregnancy should be recorded on a Clinical Trial Pregnancy form 
and reported by the investigator to the sponsor or its designee.  Pregnancy follow-up information 
should be recorded on the same form and should include an assessment of the possible causal 
relationship to the sponsor's study drug to any pregnancy outcome, as well as follow-up to the 
first well-baby visit or the duration specified in local regulations, whichever is later.  Refer to the 
Incyte Reference Guide for Completing the Clinical Trial Pregnancy Form. 
Any SAE occurring during pregnancy must be recorded on the SAE report form and 
submitted to the sponsor or designee. 


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8.6. 
Warnings and Precautions 
Special warnings or precautions for the study drug, derived from safety information collected by 
the sponsor or its designee, are presented in the IB.  Additional safety information collected 
between IB updates will be communicated in the form of Investigator Notifications (INs).  Any 
important new safety information should be discussed with the subject during the study, as 
necessary.  If new significant risks are identified, they will be added to the ICF. 
8.7. 
Data Monitoring Committee 
Not applicable. 
8.8. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 
All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported to the sponsor.  All product complaints associated with other 
study material will be reported directly to the respective manufacturer. 
The investigator or his/her designee is responsible for reporting a complete description of the 
product complaint via email or other written communication to the sponsor contact or respective 
manufacturer as noted in the packaging information.  Any AE associated with a product 
complaint should be reported as described in Section 8.1.2 of this Protocol. 
If the investigator is asked to return the product for investigation, he/she will return a copy of the 
product complaint communication with the product. 
9. 
STATISTICS 
9.1. 
Study Populations 
The efficacy evaluable population includes all subjects who have a known FGF/FGFR alteration 
from the central genomics laboratory and received at least 1 dose of study drug, and all subjects 
in the US who have a negative FGF/FGFR alteration from the central genomics laboratory and 
received at least 1 dose of study drug. 
The per protocol (PP) population includes all efficacy subjects who were sufficiently compliant 
with the Protocol. 
The safety population includes all subjects who received at least 1 dose of study drug. 
9.2. 
Selection of Sample Size 
Approximately 100 subjects with documentation of FGFR2 translocation from the central 
genomics laboratory are planned for the final analysis of the primary endpoint of ORR.  With the 
assumed rates of 33% for the intervention, a sample size of approximately 100 subjects would 
provide > 95% probability to have a 95% confidence interval with lower limit of > 15% 


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assuming 10% lost to follow-up.  Up to 20 subjects will be enrolled in Cohorts B and C (US 
only), respectively, which will provide > 80% chance of observing at least 4 responders in each 
cohort if the underlying ORR is 30%. 
9.3. 
Level of Significance 
The level of significance for the primary endpoint is 1-sided 5%. 
9.4. 
Statistical Analyses 
Subjects will be summarized by cohorts, and cohort determination will be based on FGF/FGFR 
status from the central genomics laboratory. 
9.4.1. 
Efficacy Analyses 
9.4.1.1. 
Primary Efficacy Analyses 
The primary endpoint of the study is ORR in subjects with FGFR2 translocations based on the 
central genomics laboratory results, defined as the proportion of subjects who achieved a CR or a 
PR based on RECIST v1.1 as assessed by an independent centralized radiological review 
committee.  This analysis will be based on efficacy evaluation population.  Subjects who do not 
have sufficient baseline or on-study response assessment information to be adequately assessed 
for response status will be included in the denominators in the calculation of ORR.  The 95% CI 
for the ORR will be estimated using the Clopper-Pearson method. 
The ORR will also be analyzed based on per protocol population as sensitivity analysis. 
9.4.1.2. 
Secondary Efficacy Analyses 
Secondary efficacy analysis will be conducted for the efficacy evaluable population.  
Objective response rate in subjects with FGF/FGFR alterations other than FGFR2 translocations, 
in subjects negative for FGF/FGFR alteration and in all subjects with FGF/FGFR alterations will 
be analyzed in the same fashion as the primary analysis. 
For objective responders, DOR is defined as the time from the date that a subject first achieves 
CR or PR based on RECIST v1.1 until the date of first documented disease progression based on 
RECIST v1.1 or death.  Subjects who are alive without progression before analysis cut-off date 
will be censored.  Censoring of DOR will follow the same algorithm as the censoring of PFS.  
Duration of response data will be analyzed by the Kaplan-Meier method for all cohorts. 
Disease control rate, defined as the proportion of subjects who achieved CR, PR, or SD per 
RECIST v1.1 will be analyzed in the same fashion as the primary analysis. 
Progression-free survival is defined as the time from the first day of taking study dose to the 
earlier of death or disease progression by RECIST v1.1 as assessed by the central radiographic 
review committee.  Subjects who are alive without progression before analysis cut-off date will 
be censored.  Censoring for PFS will follow FDA guidance.  Progression-free survival data will 
be analyzed by the Kaplan-Meier method for all cohorts. 


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Overall survival is defined as the number of days from the first day taking study drug to death 
due to any cause.  Subjects without death observed at the time of the analysis will be censored at 
last date known to be alive.  Overall survival will be analyzed by the Kaplan-Meier method. 
 
 
 
 
 
 
 
9.4.2. 
Safety Analyses 
9.4.2.1. 
Adverse Events 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after 
first dose of study drug.  Analysis of AEs will be limited to TEAEs, but data listings will include 
all AEs regardless of their timing to study drug administration.  Adverse events will be tabulated 
by the MedDRA preferred term and system organ class.  Severity of AEs will be based on the 
National Cancer Institute (NCI) CTCAE v4.03 using Grades 1 through 4 (NCI 2010). 
The subset of AEs considered by the investigator to have a relationship to study drug will be 
considered to be treatment-related AEs.  If the investigator does not specify the relationship of 
the AE to study drug, the AE will be considered treatment-related.  The incidence of AEs and 
treatment-related AEs will be tabulated. 
Subjects taking INCB054828 may develop HP, which is a known effect of selective FGFR 
inhibitors.  The number and percentage of subjects with at least 1 event of HP will be tabulated. 
9.4.2.2. 
Clinical Laboratory Tests 
Laboratory test values outside the normal range will be assessed for severity based on the normal 
ranges for the clinical reference laboratory.  The incidence of abnormal laboratory values and 
shift tables relative to baseline will be tabulated. 
Laboratory data will be classified into Grades 1 through 4 using CTCAE v4.03.  The following 
summaries will be produced for the laboratory data: 
• Number and percentage of subjects with worst postbaseline CTCAE grade (regardless 
of baseline value).  Each subject will be counted only for the worst grade observed 
postbaseline. 
• Shift tables from baseline to the worst postbaseline value using CTCAE grade. 
• For laboratory parameters where CTCAE grades are not defined, shift tables to the 
worst postbaseline value using the low/normal/high classifications based on 
laboratory reference ranges. 


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9.4.2.3. 
Vital Signs 
Descriptive statistics and mean change from baseline will be determined for vital signs (blood 
pressure, pulse, respiratory rate, and body temperature) at each assessment time.  Vital sign 
results will be reviewed for clinically notable abnormalities (see Table 9), and subjects exhibiting 
clinically notable vital sign abnormalities will be listed.  A value will be considered an "alert" 
value if it is outside the established range and shows a > 25% change from baseline. 
Table 9: 
Criteria for Clinically Notable Vital Sign Abnormalities 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
> 155 mmHg 
< 85 mmHg 
Diastolic blood pressure 
> 100 mmHg 
< 40 mmHg 
Pulse 
> 100 bpm 
< 45 bpm 
Temperature 
> 38ºC 
< 35.5ºC 
Respiratory rate 
> 24/min 
< 8/min 
9.4.2.4. 
Electrocardiograms 
Descriptive statistics and mean change from baseline will be determined for each ECG parameter 
at each assessment time.  Electrocardiogram results will be reviewed for clinically notable 
abnormalities according to predefined criteria (Table 10).  Subjects exhibiting clinically notable 
ECG abnormalities will be listed. 
Table 10: 
Criteria for Clinically Notable Electrocardiogram Abnormalities 
Parameter 
High Threshold 
Low Threshold 
QTcF 
> 450 msec 
< 295 msec 
PR 
> 220 msec 
< 75 msec 
QRS 
> 120 msec 
< 50 msec 
QT 
> 500 msec 
< 300 msec 
QTcF = Fridericia correction. 
9.4.3. 
Pharmacokinetic Analysis 
The data will be analyzed by standard population PK methods using appropriate software (eg, 
NONMEM).  An attempt will be made to evaluate the effect of demographic characteristics and 
baseline characteristics (eg, age, weight, sex, race, renal function, FGF/FGFR alteration status) 
on the population PK profile.  Additionally, exposure-response analyses for key efficacy and 
safety parameters will also be considered if there is sufficient data available (Appendix C). 
9.5. 
Analyses for the Data Monitoring Committee 
Not applicable. 
9.6. 
Futility Analysis 
For Cohort A (FGFR2 translocation), futility analysis will be performed when approximately 
25 subjects are enrolled into the cohort and have at least 1 tumor assessment or have permanently 
discontinued study treatment.  Cohort A can be stopped for futility if 2 or less responders are 


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observed, for which there is less than 10% probability of claiming ORR > 15% based on a 
60 subject cohort, as initially planned before Amendment 5.  This rule is just a guidance and 
nonbinding. 
Cohorts B (other FGF/FGFR alterations) and C (US only; negative for FGF/FGFR alterations) 
can be stopped if 1 or less responders are observed within the first 10 subjects who have at least 
2 cycles of data.  This is just a guidance and nonbinding. 
10. 
ETHICAL CONSIDERATIONS AND ADMINISTRATIVE 
PROCEDURES 
10.1. 
Investigator Responsibilities 
This study will be performed in accordance with ethical principles that originate in the 
Declaration of Helsinki and conducted in adherence to the study Protocol; GCPs as defined in 
Title 21 of the US CFR Parts 11, 50, 54, 56, and 312; ICH E6 GCP consolidated guidelines; and 
local regulatory requirements as applicable to the study locations. 
The investigator will be responsible for: 
• Permitting study-related monitoring, sponsor audits, IRB/IEC review, and regulatory 
inspections by providing direct access to source data and other relevant clinical study 
documents. 
− Monitoring:  Qualified representatives of the sponsor or its designee, study 
monitors, will monitor the study according to a predetermined plan.  The 
investigator must allow the study monitors to review any study materials and 
subject records at each monitoring visit. 
− Auditing:  Qualified representatives of the sponsor or its designee may audit the 
clinical study site and study data to evaluate compliance with the Protocol, 
applicable local clinical study regulations, and overall study conduct.  The 
investigator must allow the auditors to review original source records and study 
documentation for all subjects. 
− Regulatory inspection:  Regulatory authorities may conduct an inspection of the 
study and the site at any time during the development of an investigational 
product.  The investigator and staff are expected to cooperate with the inspectors 
and allow access to all source documents supporting the eCRFs and other 
study-related documents.  The investigator must immediately notify the sponsor 
when contacted by any regulatory authority for the purposes of conducting an 
inspection. 
• Obtaining informed consent and ensuring that the study subjects' questions have been 
answered and the subjects fully understand study procedures: 
− Informed consent must be obtained before any study-related procedures are 
conducted, unless otherwise specified by the Protocol. 


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− Informed consent must be obtained using the IRB/IEC-approved version in a 
language that is native and understandable to the subject.  A template will be 
provided by the sponsor or its designee.  The sponsor or its designee must review 
and acknowledge the site-specific changes to the ICF template.  The ICF must 
include a statement that the sponsor or its designee and regulatory authorities have 
direct access to subject records. 
• Obtaining approval from the IRB/IEC before the start of the study and for any 
changes to the clinical study Protocol, important Protocol deviations, routine updates, 
and safety information in accordance with institutional requirements and local law. 
− The investigator is responsible for ensuring that the safety reports provided by the 
sponsor are reviewed and processed in accordance with regulatory requirements 
and with the policies and procedures established by the IRB/IEC. 
• Adhering to the Protocol as described in this document and agreeing that changes to 
the Protocol procedures, with the exception of medical emergencies, must be 
discussed and approved, first, by the sponsor or its designee and, second, by the 
IRB/IEC.  Each investigator is responsible for enrolling subjects who have met the 
specified eligibility criteria. 
• Retaining records in accordance with all local, national, and regulatory laws, but for a 
minimum period of at least 2 years after the last marketing application approval in an 
ICH region and until there are no pending or contemplated marketing applications in 
an ICH region, or if not approved, 2 years after the termination of the test article for 
investigation to ensure the availability of study documentation should it become 
necessary for the sponsor or a regulatory authority to review. 
− The investigator must not destroy any records associated with the study without 
receiving approval from the sponsor.  The investigator must notify the sponsor or 
its designee in the event of accidental loss or destruction of any study records.  If 
the investigator leaves the institution where the study was conducted, the sponsor 
or its designee must be contacted to arrange alternative record storage options. 
− All eCRF data entered by the site (including audit trail), as well as computer 
hardware and software (for accessing the data), will be maintained or made 
available at the site in compliance with applicable record retention regulations.  
The sponsor will retain the original eCRF data and audit trail. 
10.2. 
Accountability, Handling, and Disposal of Study Drug 
The investigator is responsible for drug accountability at the study site; however, some of the 
drug accountability duties may be assigned to an appropriate pharmacist or other designee.  
Inventory and accountability records must be maintained and readily available for inspection by 
the study monitor and are open to inspection at any time by any applicable regulatory authorities.  
The investigator or designee must maintain records that document: 
• Delivery of study drug to the study site. 
• Inventory of study drug at the site. 


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• Subject use of the study drug including pill or unit counts from each supply 
dispensed. 
• Return of study drug to the investigator or designee by subjects. 
The investigational product must be used only in accordance with the Protocol.  The investigator 
will also maintain records adequately documenting that the subjects were provided the specified 
study drug.  These records should include dates, quantities, and any available batch or serial 
numbers or unique code numbers assigned to the investigational product and study subjects. 
Completed accountability records will be archived by the site.  The investigator or designee will 
be expected to collect and retain all used, unused, and partially used containers of study drug 
until verified by the study monitor (unless otherwise agreed to by the sponsor).  At the 
conclusion of the study, the investigator or designee will oversee shipment of any remaining 
study drug back to the sponsor or its designee for destruction according to institutional standard 
operating procedures.  If local procedures mandate on-site destruction of investigational supply, 
the site should (where local procedures allow) maintain the investigational supply until the study 
monitor inspects the accountability records in order to evaluate compliance and accuracy of 
accountability by the investigative site.  At sites where the study drug is destroyed before 
monitor inspection, the monitors rely on documentation of destruction per the site SOP. 
10.3. 
Data Management 
Data management will be performed in a validated database via an Electronic Data Capture 
(EDC) system.  All data entry, verification, and validation will be performed in accordance with 
the current standard operating procedures of the Data Management Department at the sponsor or 
its designee.  The database will be authorized for lock once all defined procedures are completed. 
The investigator will be provided with access to an EDC system so that an eCRF can be 
completed for each subject.  Entries made in the eCRF must be verifiable against source 
documents; if updates to the database are not possible, any discrepancies should be explained 
and documented.  The investigator will be responsible for reviewing all data and eCRF entries, 
and will sign and date the designated forms in each subject's eCRF, verifying that the 
information is true and correct.  The investigator is responsible for the review and approval of all 
query responses. 
Protocol deviations will be identified and recorded in the Protocol Deviation form of the eCRF.  
The study monitor will reference the Monitoring Plan in order to ensure that each issue identified 
is appropriately documented, reported, and resolved in a timely manner in accordance with the 
plan's requirements. 
10.4. 
Data Privacy and Confidentiality of Study Records 
The investigator and the sponsor or its designee must adhere to applicable data privacy laws and 
regulations.  The investigator and the sponsor or its designee are responsible for ensuring that 
sensitive information is handled in accordance with local requirements (eg, HIPAA).  
Appropriate consent and authorizations for use and disclosure and/or transfer (if applicable) of 
protected information must be obtained. 


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Subject names will not be supplied to the sponsor or its designee, if applicable.  Only the subject 
number and subject's initials (subject's initials will only be recorded if allowable by local 
regulations) will be recorded in the eCRF, where permitted; if the subject's name appears on any 
other document (eg, laboratory report), it must be obliterated on the copy of the document to be 
supplied to the sponsor or its designee.  Study findings stored on a computer will be stored in 
accordance with local data protection laws.  The subjects will be informed that representatives of 
the sponsor or its designee, IRB or IEC, or regulatory authorities may inspect their medical 
records to verify the information collected, and that all personal information made available for 
inspection will be handled in strictest confidence and in accordance with local data protection 
laws. 
10.5. 
Financial Disclosure 
Before study initiation, all clinical investigators participating in clinical studies subject to FDA 
Regulation Title 21 Code of Federal Regulations (CFR) Part 54 – Financial Disclosure by 
Clinical Investigators (ie, "covered studies") are required to submit a completed Clinical 
Investigator Financial Disclosure form that sufficiently details any financial interests and 
arrangements that apply.  For the purpose of this regulation, "clinical investigator" is defined as 
any investigator or subinvestigator who is directly involved in the treatment or evaluation of 
research subjects, including the spouse and each dependent child of the clinical investigator or 
subinvestigator.  These requirements apply to both US and foreign clinical investigators 
conducting covered clinical studies. 
Any new clinical investigators added to the covered clinical study during its conduct must also 
submit a completed Investigator Financial Disclosure Form.  During a covered clinical study, 
any changes to the financial information previously reported by a clinical investigator must be 
reported to the sponsor or its designee.  At the conclusion of the covered clinical study, the 
clinical investigators will be reminded of their obligations.  In the event that the clinical 
investigator is not reminded, they nevertheless will remain obligated to report to the sponsor or 
its designee any changes to the financial information previously reported, as well as any changes 
in their financial information for a period of 1 year after completion of the covered clinical study. 
10.6. 
Publication Policy 
By signing the study Protocol, the investigator and his or her institution agree that the results of 
the study may be used by the sponsor, Incyte Corporation (Incyte), for the purposes of national 
and international registration, publication, and information for medical and pharmaceutical 
professionals.  Study results will be published in accordance with applicable local and national 
regulations.  If necessary, the authorities will be notified of the investigator's name, address, 
qualifications, and extent of involvement.  The terms regarding the publication of study results 
are contained in the agreement signed with the sponsor or its designee.  A signed agreement will 
be retained by the sponsor or its designee. 


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11. 
REFERENCES 
Ang C. Role of the fibroblast growth factor receptor axis in cholangiocarcinoma. J Gastroenterol 
Hepatol 2015;30:1116-1122. 
Arai Y, Totoki Y, Hosoda F, et al. Fibroblast growth factor receptor 2 tyrosine kinase fusions 
define a unique molecular subtype of cholangiocarcinoma. Hepatology 2014;59:1427-1434. 
Arora A, Scholar EM. Role of tyrosine kinase inhibitors in cancer therapy. J Pharmacol Exp Ther 
2005;315:971-979. 
Baum M, Schiavi S, Dwarakanath V, Quigley R. Effect of fibroblast growth factor-23 on 
phosphate transport in proximal tubules. Kidney Int 2005;68:1148-1153. 
Bergquist A, von Seth E. Epidemiology of cholangiocarcinoma. Best Pract Res Clin 
Gastroenterol 2015;29:221-232. 
Blechacz BR, Gores GJ. Cholangiocarcinoma. Clin Liver Dis 2008;12:131-150. 
Brown AP, Courtney CL, King LM, Groom SC, Graziano MJ. Cartilage dysplasia and tissue 
mineralization in the rat following administration of a FGF receptor tyrosine kinase inhibitor. 
Toxicol Pathol 2005;33:449-455. 
 
  
 
Churi CR, Shroff R, Wang Y, et al. Mutation profiling in cholangiocarcinoma: prognostic and 
therapeutic implications. PLoS One 2014;9:e115383. 
Clinical Trial Facilitation Group (CTFG). Recommendations related to contraception and 
pregnancy testing in clinical trials. September 15, 2014. http://www.hma.eu/ctfg.html. Accessed 
May 25, 2016. 
Dailey L, Ambrosetti D, Mansukhani A, Basilico C. Mechanisms underlying differential 
responses to FGF signaling. Cytokine Growth Factor Rev 2005;16:233-247. 
Donnem T, Al-Shibli K, Al-Saad S, Busund LT, Bremnes RM. Prognostic impact of fibroblast 
growth factor 2 in non-small cell lung cancer: coexpression with VEGFR-3 and PDGF-B 
predicts poor survival. J Thorac Oncol 2009;4:578-585. 
Eckman KR, Patel DK, Landgraf A, et al. Chemotherapy outcomes for the treatment of 
unresectable intrahepatic and hilar cholangiocarcinoma: a retrospective analysis. Gastrointest 
Cancer Res 2011; 4:155-160. 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors: 
revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-247. 
Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. 
Cytokine Growth Factor Rev 2005;16:139-149. 


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Farrow EG, White KE. Recent advances in renal phosphate handling. Nat Rev Nephrol 
2010;6:207-217. 
 
 
Fuks Z, Persaud RS, Alfieri A, et al. Basic fibroblast growth factor protects endothelial cells 
against radiation-induced programmed cell death in vitro and in vivo. Cancer Res 1994;54:2582 
2590. 
Graham RP, Barr Fritcher EG, Pestova E, et al. Fibroblast growth factor receptor 2 translocations 
in intrahepatic cholangiocarcinoma. Human Pathology 2014;45:1630-1638. 
Guagnano V, Kauffmann A, Wöhrle S, et al. FGFR genetic alterations predict for sensitivity to 
NVP-BGJ398, a selective pan-FGFR inhibitor. Cancer Discov 2012;2:1118-1133. 
INCB054828 Investigator's Brochure (IB). Wilmington, DE: Incyte Corporation. 
Itoh N. Hormone-like (endocrine) Fgfs: their evolutionary history and roles in development, 
metabolism, and disease. Cell Tissue Res 2010;342:1-11. 
Javle M, Lowery M, Shroff RT, et al. Phase II Study of BGJ398 in Patients With FGFR-Altered 
Advanced Cholangiocarcinoma. J Clin Oncol 2018;36:276-282. 
Knights V, Cook SJ. De-regulated FGF receptors as therapeutic targets in cancer. Pharmacol 
Ther 2010;125:105-117. 
Kunii K, Davis L, Gorenstein J, et al. FGFR2-amplified gastric cancer cell lines require FGFR2 
and Erbb3 signaling for growth and survival. Cancer Res 2008;68:2340-2348. 
Lamont FR, Tomlinson DC, Cooper PA, Shnyder SD, Chester JD, Knowles MA. Small molecule 
FGF receptor inhibitors block FGFR-dependent urothelial carcinoma growth in vitro and in vivo. 
Br J Cancer 2011;104:75-82. 
National Cancer Institute (NCI). Common Terminology Criteria for Adverse Events (CTCAE) 
Version 4.03. 2010. http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-
14_QuickReference_5x7.pdf. Accessed October 14, 2014. 
National Cancer Institute (NCI). SEER Stat Fact Sheets: Liver and Intrahepatic Bile Duct 
Cancer. 2016. http://seer.cancer.gov/statfacts/html/livibd.html. Accessed June 1, 2016. 
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol 1982;5:649-655. 
Pai R, French D, Ma N, et al. Antibody-mediated inhibition of fibroblast growth factor 19 results 
in increased bile acids synthesis and ileal malabsorption of bile acids in cynomolgus monkeys. 
Toxicol Sci 2012;126:446-456. 
Pardo OE, Arcaro A, Salerno G, Raguz S, Downward J, Seckl MJ. Fibroblast growth factor-2 
induces translational regulation of Bcl-XL and Bcl-2 via a MEK-dependent pathway: correlation 
with resistance to etoposide-induced apoptosis. J Biol Chem 2002;277:12040-12046. 
Qing J, Du X, Chen Y, et al. Antibody-based targeting of FGFR3 in bladder carcinoma and 
t(4;14)-positive multiple myeloma in mice. J Clin Invest 2009;119:1216-1229. 


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Rades D, Setter C, Dahl O, Schild SE, Noack F. Fibroblast growth factor 2--a predictor of 
outcome for patients irradiated for stage II-III non-small-cell lung cancer. Int J Radiat Oncol Biol 
Phys 2012;82:442-447. 
Rizvi S, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. 
Gastroenterology 2013;145:1215-1229. 
Ross JS, Wang K, Gay L, Al-Rohil R, et al. New routes to targeted therapy of intrahepatic 
cholangiocarcinomas revealed by next-generation sequencing. Oncologist 2014;19:235-242. 
Shimada T, Hasegawa H, Yamazaki Y, et al. FGF-23 is a potent regulator of vitamin D 
metabolism and phosphate homeostasis. J Bone Miner Res 2004a;19:429-435. 
Shimada T, Mizutani S, Muto T, et al. Cloning and characterization of FGF23 as a causative 
factor of tumor-induced osteomalacia. Proc Natl Acad Sci USA 2001;98:6500-6505. 
Shimada T, Urakawa I, Yamazaki Y, et al. FGF-23 transgenic mice demonstrate 
hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa. 
Biochem Biophys Res Commun 2004b;314:409-414. 
Terai H, Soejima K, Yasuda H, et al. Activation of the FGF2-FGFR1 autocrine pathway: a novel 
mechanism of acquired resistance to gefitinib in NSCLC. Mol Cancer Res 2013;11:759-767. 
Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev 
Cancer 2010;10:116-129. 
Weiss J, Sos ML, Seidel D, et al. Frequent and focal FGFR1 amplification associates with 
therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med 
2010;2:62ra93. 
Wöhrle S, Bonny O, Beluch N, et al. FGF receptors control vitamin D and phosphate 
homeostasis by mediating renal FGF-23 signaling and regulating FGF-23 expression in bone. 
J Bone Mineral Res 2011;26:2486-2497. 
Wu YM, Su F, Kalyana-Sundaram S, et al. Identification of targetable FGFR gene fusions in 
diverse cancers. Cancer Discov 2013;3:636-647. 
Yanochko GM, Vitsky A, Heyen JR, et al. Pan-FGFR inhibition leads to blockade of FGF23 
signaling, soft tissue mineralization, and cardiovascular dysfunction. Toxicol Sci 2013;135:451-
464. 


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APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS 
For Subjects Participating in the Study: 
The following methods that can achieve a failure rate of less than 1% per year when used 
consistently and correctly are considered as highly effective birth control methods.  
Such methods include: 
• Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation1 
− oral 
− intravaginal 
− transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation1 
− oral 
− injectable 
− implantable2 
• Intrauterine device (IUD)2 
• Intrauterine hormone-releasing system (IUS)2 
• Bilateral tubal occlusion2 
• Vasectomised partner2,3 
• Sexual abstinence4 
 
1  Hormonal contraception may be susceptible to interaction with the IMP, which may reduce the efficacy of the 
contraception method. 
2  Contraception methods that in the context of this guidance are considered to have low user dependency. 
3  Vasectomised partner is a highly effective method provided of avoiding pregnancy that partner is the sole sexual 
partner of the WOCBP trial participant and that the vasectomised partner has received medical assessment of the 
surgical success.  
4  In the context of this guidance, sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the study treatments.  The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the 
preferred and usual lifestyle of the subject. 
Source:  CTFG 2014. 


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APPENDIX B. CYP3A4 INDUCERS AND INHIBITORS 
CYP3A Inducers 
Inducers 
Therapeutic class 
Potent CYP3A Inducers  
Rifampin 
Antibiotics  
Mitotane 
Other Antineoplastics  
Avasimibe 
Other Antilipemics  
Rifapentine 
Antibiotics  
Apalutamide 
Antiandrogens  
Phenytoin 
Anticonvulsants 
Carbamazepine 
Anticonvulsants 
Enzalutamide 
Antiandrogens 
St John's Wort extract 
Herbal medications 
Lumacaftor 
Cystic fibrosis treatments 
Rifabutin 
Antibiotics 
Phenobarbital 
Anticonvulsants 
Moderate CYP3A Inducers  
Ritonavir and St. Johns wort 
None 
Semagacestat 
Alzheimer's treatments 
Efavirenz 
NNRTIs 
Tipranavir and ritonavir 
Protease inhibitors 
Dabrafenib 
Kinase inhibitors 
Lesinurad 
Antigout and uricosuric agents 
Bosentan 
Endothelin receptor antagonists 
Genistein 
Food products 
Thioridazine 
Antipsychotics 
Nafcillin 
Antibiotics 
Talviraline 
NNRTIs 
Lopinavir 
Protease inhibitors 
Modafinil 
Psychostimulants 
Pf-06282999 
Myeloperoxidase inactivators 
Etravirine 
NNRTIs 
Lersivirine 
NNRTIs 
Telotristat ethyl 
Antidiarrheals 
 


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CYP3A Inhibitors 
Inhibitor 
Therapeutic Class 
Potent CYP3A Inhibitors  
VIEKIRA PAK 
Antivirals 
Indinavir /RIT 
Protease inhibitors 
Tipranavir/RIT 
Protease inhibitors 
Ritonavir 
Protease inhibitors 
Cobicistat (GS-9350) 
None 
Ketoconazole 
Antifungals 
Indinavir 
Protease inhibitors 
Troleandomycin 
Antibiotics 
Telaprevir 
Antivirals 
Danoprevir/RIT 
Antivirals 
Elvitegravir/RIT 
Treatments of AIDS 
Saquinavir/RIT 
Protease inhibitors 
Lopinavir/RIT 
Protease inhibitors 
Itraconazole 
Antifungals 
Voriconazole 
Antifungals 
Mibefradil 
Calcium channel blockers 
LCL161 
Cancer treatments 
Clarithromycin 
Antibiotics 
Posaconazole 
Antifungals 
Telithromycin 
Antibiotics 
Grapefruit juice DS 
Food products 
Conivaptan 
Diuretics 
Nefazodone 
Antidepressants 
Nelfinavir 
Protease inhibitors 
Saquinavir 
Protease inhibitors 
Ribociclib 
Kinase inhibitors 
Idelalisib 
Kinase inhibitors 
Boceprevir 
Antivirals 
Moderate CYP3A Inhibitors  
Erythromycin 
Antibiotics 
Fluconazole 
Antifungals 
Atazanavir/RIT 
Protease inhibitors 


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Inhibitor 
Therapeutic Class 
Darunavir 
Protease inhibitors 
Diltiazem 
Calcium channel blockers 
Darunavir/RIT 
Protease inhibitors 
Dronedarone 
Antiarrhythmics 
Crizotinib 
Kinase inhibitors 
Atazanavir 
Protease inhibitors 
Letermovir 
Antivirals 
GSK2647544 
Alzheimer's disease & dementia treatments 
Aprepitant 
Antiemetics 
Casopitant 
Antiemetics  
Amprenavir 
Protease inhibitors 
Faldaprevir 
Antivirals 
Imatinib 
Antineoplastic agents 
Verapamil 
Calcium channel blockers 
Netupitant 
Antiemetics 
Nilotinib 
Kinase inhibitors 
Grapefruit juice 
Food products 
Tofisopam 
Benzodiazepines 
Cyclosporine 
Immunosuppressants 
ACT-178882 
Renin inhibitors 
Ciprofloxacin 
Antibiotics 
Magnolia vine (Schisandra sphenanthera) 
Herbal medications 
Isavuconazole 
Antifungals 
Cimetidine 
H-2 receptor antagonists 
FK1706 
Central nervous system agents 
 


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APPENDIX C. PHARMACOKINETIC ANALYTICAL PARAMETERS 
Cave 
Average steady-state plasma concentration (AUC0-12h/12h or 
AUC0-24h/24h) 
Cmax 
Maximum observed plasma concentration 
Cmin 
Minimum observed plasma concentration during the dosing interval 
Tmax 
Time to maximum plasma concentration 
AUC0-t 
Area under the single-dose plasma concentration-time curve from Hour 0 
to the last quantifiable measurable plasma concentration, calculated by the 
linear trapezoidal rule for increasing concentrations and the log 
trapezoidal rule for decreasing concentrations 
AUC0-τ (ie, 
AUC0-12h or 
AUC0-24h) 
Area under the steady-state plasma concentration-time curve over 
1 dosing interval (ie, from Hour 0 to 12 for BID administration or from 
Hour 0 to 24 for QD administration), calculated by the linear trapezoidal 
rule for increasing concentrations and the log trapezoidal rule for 
decreasing concentrations 
λz 
Apparent terminal phase disposition rate constant, where λz is the 
magnitude of the slope of the linear regression of the log concentration 
versus time profile during the terminal phase 
t½ 
Apparent plasma terminal phase disposition half-life (whenever possible), 
where t½ = (ln2) / λz 
Cl/F 
Oral dose clearance 
Vz/F 
Apparent oral dose volume of distribution 
Fluctuation 
Steady-state fluctuation ([Cmax – Cmin]/Cave) 
In addition, the following PK parameters may be calculated, whenever possible, for each subject 
based on the urine INCB054828 concentrations: 
Ae 
Amount of drug excreted in the urine over sampling interval 
Clr 
Renal clearance, where Clr = Ae/AUC 
% Excreted or fe 
percent excreted in the urine, where % Excreted = 100 (Ae/dose) 
Pharmacokinetic calculations will be performed, if appropriate, using commercial software such 
as WinNonlin®.  Additional details of analyses will be described in the statistical analysis plan. 


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APPENDIX D. FGF/FGFR ALTERATIONS 
Please follow instructions outline in the Investigator Site Files for screening/enrolling subjects.  
This list contains recurrent FGF/FGFR alterations that have been previously described or are 
present in somatic mutation databases and is not inclusive of all possible alterations.  For 
FGF/FGFR alterations not present on this list, please consult with the study sponsor. 
Cohort 
Gene 
Alteration 
A 
FGFR2 
Novel FGFR2 fusions 
 
A 
FGFR2 
FGFR2
 
A 
FGFR2 
FGFR2
 
A 
FGFR2 
FGFR2
 
A 
FGFR2 
FGFR2
 
A 
FGFR2 
FGFR2
 
A 
FGFR2 
FGFR2
 
A 
FGFR2 
FGFR2
 
A 
FGFR2 
FGFR2
 
A 
FGFR2 
FGFR2
 
A 
FGFR2 
FGFR2
 
A 
FGFR2 
FGFR2
 
B 
FGFR2 
FGFR2 Rearrangement (N/A Partner) 
B 
FGFR2 
FGFR2 Rearrangement 
B 
FGFR2 
R203C 
B 
FGFR2 
R210Q 
B 
FGFR2 
S252W 
B 
FGFR2 
P253R 
B 
FGFR2 
P253L 
B 
FGFR2 
W290C 
B 
FGFR2 
S320C 
B 
FGFR2 
S372C 
B 
FGFR2 
Y375C 
B 
FGFR2 
Y375H 
B 
FGFR2 
C382R 
B 
FGFR2 
C382Y 
B 
FGFR2 
V395D 


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Cohort 
Gene 
Alteration 
B 
FGFR2 
D471N 
B 
FGFR2 
D471Q 
B 
FGFR2 
M537I 
B 
FGFR2 
N549K 
B 
FGFR2 
N549H 
B 
FGFR2 
N549D 
B 
FGFR2 
N549S 
B 
FGFR2 
N549Y 
B 
FGFR2 
E596K 
B 
FGFR2 
K659E 
B 
FGFR2 
K659N 
B 
FGFR2 
K659M 
B 
FGFR2 
R664W 
B 
FGFR2 
Amplification 
B 
FGFR1 
R445W 
B 
FGFR1 
N546K 
B 
FGFR1 
K656E 
B 
FGFR1 
K656M 
B 
FGFR1 
Amplification 
B 
FGFR1 
Novel FGFR1 Fusions (
) 
B 
FGFR1 
FGFR1
 
B 
FGFR1 
FGFR1
 
B 
FGFR1 
FGFR1
 
B 
FGFR1 
FGFR1
 
B 
FGFR1 
FGFR1 
B 
FGFR1 
FGFR1 
B 
FGFR1 
FGFR1 
B 
FGFR1 
FGFR1 
B 
FGFR1 
FGFR1 
B 
FGFR3 
R248C 
B 
FGFR3 
S249C 
B 
FGFR3 
G370C 


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Cohort 
Gene 
Alteration 
B 
FGFR3 
S371C 
B 
FGFR3 
Y373C 
B 
FGFR3 
G380R 
B 
FGFR3 
G380E 
B 
FGFR3 
A391E 
B 
FGFR3 
R399C 
B 
FGFR3 
S433C 
B 
FGFR3 
D641N 
B 
FGFR3 
K650M 
B 
FGFR3 
K650E 
B 
FGFR3 
K650Q 
B 
FGFR3 
K650T 
B 
FGFR3 
K650N 
B 
FGFR3 
Amplification 
B 
FGFR3 
Novel FGFR3 fusion (
) 
B 
FGFR3 
FGFR3
 
B 
FGFR3 
FGFR3
 
B 
FGFR3 
FGFR3
 
B 
FGFR3 
FGFR3
 
B 
 
FRS2 
B 
fgf10 
Amplification 
B 
fgf14 
Amplification 
B 
fgf19 
Amplification 
B 
fgf23 
Amplification 
B 
fgf3 
Amplification 
B 
fgf4 
Amplification 
B 
fgf6 
Amplification 
C 
NO FGFR/FGF ALTERATION NOTED 
 


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APPENDIX E. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Document 
Date 
Amendment (Version) 1: 
14 SEP 2016 
Amendment (Version) 2: 
05 DEC 2016 
Amendment (Version) 3: 
18 JAN 2017 
Amendment (Version) 4: 
21 MAR 2017 
Amendment (Version) 5: 
03 OCT 2017 
Amendment (Version) 6: 
15 FEB 2018 
Amendment (Version) 7: 
02 APR 2020 
Amendment 7 (02 APR 2020) 
Overall Rationale for the Amendment:  To incorporate previous administrative changes and 
include updated language for comprehensive eye examination, per FDA feedback. 
1. Synopsis 
Description of change:  Added 
, MD, as the coordinating principal 
investigator for this study. 
Rationale for change:  To identify the coordinating principal investigator of this study. 
2. Section 5.4.2, Criteria and Procedures for Dose Interruptions and Adjustments of 
Pemigatinib (Table 13: Guidelines for Interruption and Restarting of Pemigatinib) 
Description of change:  Language was added regarding guidelines for treatment 
associated with SRD/RPED. 
Rationale for change:  To provide specific guidance not included in previous versions of 
the Protocol. 
3. Section 5.7.1, Restricted Medications; Section 5.7.2, Prohibited Medications 
Description of change:  Restricted medications updated to remove CYP3A4 inducers 
and proton pump inhibitors and to add OCT2 substrates.  Prohibited medications updated 
to include moderate CYP3A4 inducers. 
Rationale for change:  Based on drug-drug interaction studies, concomitant use of 
moderate CYP3A4 inhibitors and OCT2 substrates may increase the potency of the study 
drug.  Proton pump inhibitors are no longer restricted to limited use. 
4. Section 6, Study Assessments (Table 5: Study Assessments); Section 7.5.5, 
Comprehensive Eye Examination 
Description of change:  Language added to include OCT as part of the regularly 
scheduled eye examinations. 
Rationale for change:  Per FDA requirement. 


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5. Section 5.7, Concomitant Medications; Appendix B, CYP3A4 Inducers and 
Inhibitors 
Description of change:  In Appendix B, the University of Washington website list was 
removed and new list provided. 
Rationale for change:  To provide updated information in a table format. 
6. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment.  


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Amendment 6 (15 FEB 2018) 
Overall Rationale for the Amendment: 
The primary purpose of this amendment is to ensure the study population is clearly identified, to 
provide guidelines for dose reductions, and to provide additional language for ophthalmologic 
testing and hyperphosphatemia grading. 
1. Synopsis; Section 1.1, Background; Section 3.1, Subject Inclusion Criteria 
Description of change:  References to the study population were updated to specify 
subjects with advanced/metastatic or surgically unresectable cholangiocarcinoma. 
Rationale for change:  To clarify the study population, per FDA request. 
2. Section 1.2, Study Rationale 
Description of change:  Updated data from the study by Javle et al. 
Rationale for change:  To reflect the most recently published data from the study. 
3. Section 1.3.3, Phototoxicity 
Description of change:  Deletion of precautionary statement based on preclinical data. 
Rationale for change:  To match the findings in the Investigator's Brochure. 
4. Section 5.4.2, Criteria and Procedures for Dose Interruptions and Adjustments of 
Study Drug 
Description of change:  Language was added to include actual doses for reduction, if 
needed. 
Rationale for change:  To clarify dose reduction levels, per FDA request. 
5. Section 7.5.5, Comprehensive Eye Examination 
Description of change:  Text was revised to add a funduscopy with digital imaging as 
part of the comprehensive eye examination and to clarify when additional assessments 
should be performed. 
Rationale for change:  To clarify the required and additional assessments. 
6. Section 8.1.2, Reporting 
Description of change:  The adverse events reporting section was updated to include 
specific guidance on grading hyperphosphatemia. 
Rationale for change:  To provide clearer and more specific guidance on grading of 
hyperphosphatemia. 


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Amendment 5 (03 OCT 2017) 
The primary purpose of this amendment is to increase the total number of patients enrolled into 
the study. 
1. Synopsis; Section 4.1, Overall Study Design; Section 4.3.1, Planned Number of 
Subjects; Section 9.2, Selection of Sample Size 
Description of change:  The total number of subjects was increased from 100 to 140; the 
number of subjects to be enrolled into Cohort A was increased from 60 to 100.  The 
probability for showing a response has been changed from 80% to 95% based on the 
increased sample size of 100 subjects in Cohort A. 
Rationale for change:  To assure the most robust efficacy data to inform future 
development decisions. 
2. Synopsis; Section 3.1, Subject Inclusion Criteria; Section 4.1, Overall Study Design  
Description of change:  The Cohort A population description was revised to include 
documented fusion partner in central laboratory report. 
Rationale for change:  To more clearly define the Cohort A population. 
3. Synopsis; Section 9.6, Futility Analysis 
Description of change:  Added language to define criteria for futility and number of 
subjects on which the futility analysis will be based. 
Rationale for change:  To define the requirements for analysis and clarify that the 
number of patients the futility will be based on is the original cohort number of 60. 
4. Section 1.2, Study Rationale 
Description of change:  The rationale for Amendment 5 has been added. 
Rationale for change:  To clarify why the current amendment is being implemented. 
5. Section 3.1, Inclusion Criteria; Section 7.5.6.4, Evaluation of FGF and FGFR 
Genetic Alterations; Appendix D, FGF/FGFR Alterations 
Description of change:  Language has been added to each section referencing new 
appendix with list of possible FGF/FGFR alterations.  Appendix D has been added with a 
list of FGF/FGFR alterations. 
Rationale for change:  To provide a list in the Protocol of the types of FGF/FGFR 
alterations that can be considered eligible for this study. 
6. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 4 (21 MAR 2017) 
The primary purpose of this amendment is to provide new language to allow subjects to enroll 
under local genomic testing results.  Updated clinical experience data have been added as well. 
1. Synopsis; Section 2.2, Study Endpoints; Section 3.1, Subject Inclusion Criteria; Section 
4.1, Overall Study Design; Section 5.5.1, Withdrawal Criteria; Section 6.1, Prescreening 
and Screening; Section 7.5.6.4, Evaluation of FGF and FGFR Genetic Alterations; 
Section 9, Statistics  
Description of change:  Language was added to the Protocol allowing subjects to enroll 
in the study based on local genomic testing results, with final results determined by 
central genomics laboratory.  Final cohort assignment for statistical analysis of primary 
and secondary endpoints will be done based on the central genomics testing results. 
Rationale for change:  To expedite enrollment of subjects. 
 
 
 
 
 
3. Synopsis; Section 3.2, Subject Exclusion Criteria 
Description of change:  Exclusion criterion #17 regarding baseline eye abnormalities 
has been updated to include retinal disorder and to eliminate specific disorders. 
Rationale for change:  To ensure that the eye abnormalities for exclusion are more 
relevant. 
4. Synopsis; Section 6, Study Assessments (Table 5, Study Assessments); Section 6.1, 
Prescreening and Screening; Section 7.1, Administration of Informed Consent Form 
Description of change:  Prescreening details were revised to indicate that prescreening is 
available for subjects without a genomic testing report or a report that is more than 
2 years old.  Prescreening allows genomic testing to be performed outside of the 28-day 
screening window.  Details regarding informed consent for prescreening were removed. 
Rationale for change:  To allow more flexibility for genomic testing in all potential 
subjects. 
5. Section 1.3.2, Potential Risks of INCB054828 Based on Clinical Safety; 
Section 1.3.2.1, Pharmacokinetic/Pharmacodynamic Summary 
Description of change:  Updated with new clinical and PK/PD data from the ongoing 
Phase 1/2 study (INCB 54828-101). 
Rationale for change:  To provide more clinical experience data. 


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6. Section 6, Study Assessments (Table 6, Laboratory Assessments; Table 7, 
Laboratory Tests:  Required Analytes); Section 7.8.5, Buccal Swab 
Description of change:  Buccal swab has been removed from the Protocol. 
Rationale:  No longer required. 
 
 
 
 
8. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 3 (18 JAN 2017) 
The primary purpose of this amendment is to update the text in the Protocol based on the 
European Union Voluntary Harmonisation Procedure (VHP) request, to clarify requirements for 
HIV screening and enrollment parameters for Cohort C. 
1. Synopsis; Section 2.2.2, Secondary Endpoints; Section 4.1, Overall Study Design; 
Section 9.2, Selection of Sample Size; Section 9.6, Futility Analysis  
Description of change:  "US only" has been added after Cohort C. 
Rationale for change:  Only subjects from the United States will be allowed to enroll in 
Cohort C. 
2. Synopsis; Section 6, Study Assessments (Table 6, Laboratory Assessments; Table 7, 
Laboratory Tests:  Required Analytes); Section 7.5.6.3, HIV Screening Test  
Description of change:  Language was added to clarify that HIV screening is required 
for subjects enrolled outside of the United States. 
Rationale for change:  Requirement from VHP review. 


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Version 7 
02 APR 2020 
CONFIDENTIAL 
Amendment 2 (05 DEC 2016) 
The primary purpose of this amendment is to update language based on Regulatory Agencies 
comments.  Updates include but are not limited to clarification of inclusion and exclusion 
criteria, the addition of updated clinical experience data, and guidance for dose reductions. 
1. Section 1.3.2, Potential Risks of INCB054828 Based on Clinical Safety 
Description of change:  Language and data were added based on new information 
available from Study INCB 54828-101. 
Rationale for change:  Data included to update the Protocol and to better assess the 
benefit risk. 
2. Section 1.3.3, Phototoxicity 
Description of change:  This section was added to include language regarding potential 
phototoxicity of INCB054828. 
Rationale for change:  Cautionary update based on the unknown phototoxicity risk 
associated with INCB054828. 
3. Section 3.1, Subject Inclusion Criteria; Section 3.2, Subject Exclusion Criteria 
Description of change:  Inclusion criterion #9 and exclusion criterion #13 have been 
revised to include text to ensure that male subjects continue using contraception for 
90 days after last dose (1 sperm cycle). 
Rationale:  Updated per European Regulatory Agency recommendation. 
4. Section 3.2, Subject Exclusion Criteria 
Description of change:  Exclusion criterion #2 was updated to ensure that treatment with 
study drug is not initiated before 28 days after completion of anticancer treatment. 
Rationale for change:  To reduce the time that subjects are held from treatment since the 
half-life of some compounds is long. 
5. Section 3.2, Subject Exclusion Criteria 
Description of changes:  Exclusion criterion #6 (abnormal laboratory parameters) was 
revised to include low potassium, exclusion criterion #24 was added to require HIV 
screening (for subjects outside of the United States) and exclusion criterion #9 was 
updated to include language per the ICH guideline E14 on QTc prolongation.  Exclusion 
criterion #25 was added to exclude subjects with vitamin D deficiencies who require high 
doses of supplements for their deficiency. 
Rationale for change:  Updated per European Regulatory Agency recommendation. 
6. Section 5.4.4,  Criteria for Permanent Discontinuation of Study Drug 
Description of change:  Added QT/QTc criterion for stopping study drug. 
Rationale for change:  Updated to be in line with ICH E14. 


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7. Synopsis; Section 6, Study Assessments (Table 5, Laboratory Assessments; Table 6, 
Laboratory Tests:  Required Analytes); Section 7.5.6.1, Pregnancy Testing 
Description of change:  Added urine pregnancy test on Day 1 of every cycle before dose 
administration. 
Rationale for change:  Updated to test for pregnancy before the start of each cycle. 
8. Section 5.4.2, Criteria and Procedures for Dose Interruptions and Adjustments of 
Study Drug 
Description of change:  Added language to provide more instructions for dose 
reductions.  
Rationale for change:  Updated per European Regulatory Agency recommendation. 
9. Section 5.5, Withdrawal of Subjects From Study Treatment 
Description of change:  Text was added to clarify that subjects may discontinue 
treatment but remain on the study for follow-up assessments.  Additional text was added 
to clarify that subjects who retrospectively do not meet inclusion/exclusion criterion may 
be allowed to stay on treatment if they are receiving clinical benefit. 
Rationale for change:  Updated per European Regulatory Agency recommendation. 
10. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
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CONFIDENTIAL 
Amendment 1 (14 SEP 2016) 

SAP_001.pdf: 
Official Title: 
NCT Number: 
Document Date: 
A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the 
Efficacy and Safety of Pemigatinib in Subjects With Advanced/Metastatic 
or Surgically Unresectable  Cholangiocarcinoma Including FGFR2 
Translocations Who Failed Previous Therapy - (FIGHT-202)
NCT02924376
Statistical Analysis Plan Amendment 1: 15 April 2019


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STATISTICAL ANALYSIS PLAN 
 
INCB 54828-202 
A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate 
the Efficacy and Safety of INCB054828 in Subjects With 
Advanced/Metastatic or Surgically Unresectable 
Cholangiocarcinoma Including FGFR2 Translocations Who Failed 
Previous Therapy 
 
 
 
 
 
IND Number: 
 
EudraCT Number: 
2016-002422-36 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Protocol Version: 
Protocol Amendment 6 dated 15 FEB 2018 
CRF Approval Date: 
27 NOV 2018 
SAP Version: 
Amendment 1 
SAP Author:  
 
 
Date of Plan: 
15 APR 2019 
 
 
This study is being conducted in compliance with good clinical practice, 
including the archiving of essential documents. 
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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ..........................................................................................................6 
1. 
INTRODUCTION ........................................................................................................7 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS.................................7 
2.1. 
Protocol and Case Report Form Version ......................................................................7 
2.2. 
Study Objectives ...........................................................................................................7 
2.2.1. 
Primary Objective .........................................................................................................7 
2.2.2. 
Secondary Objectives ...................................................................................................7 
 
7 
2.3. 
Study Endpoints ............................................................................................................8 
2.3.1. 
Primary Endpoint ..........................................................................................................8 
2.3.2. 
Secondary Endpoints ....................................................................................................8 
 
8 
3. 
STUDY DESIGN .........................................................................................................9 
3.1. 
Control of Type I Error ...............................................................................................10 
3.2. 
Sample Size Considerations .......................................................................................10 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................11 
4.1. 
Scheduled Study Evaluations and Study Periods .......................................................11 
4.1.1. 
Day 1 ...........................................................................................................................11 
4.1.2. 
Study Day ...................................................................................................................11 
4.1.3. 
Baseline Value ............................................................................................................11 
4.1.4. 
Handling of Missing and Incomplete Data .................................................................11 
4.1.5. 
Cycle Length and Duration .........................................................................................12 
4.1.6. 
Analysis Window ........................................................................................................12 
4.2. 
Variable Definitions ....................................................................................................12 
4.2.1. 
Age ..............................................................................................................................12 
4.2.2. 
Body Mass Index ........................................................................................................12 
4.2.3. 
Prior and Concomitant Medication .............................................................................12 
5. 
STATISTICAL METHODOLOGY ...........................................................................13 
5.1. 
General Methodology .................................................................................................13 
5.2. 
Treatment Groups .......................................................................................................13 
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5.3. 
Analysis Populations ..................................................................................................13 
5.3.1. 
Efficacy Evaluable Population ...................................................................................13 
5.3.2. 
Per Protocol Population ..............................................................................................13 
5.3.3. 
Safety Population ........................................................................................................14 
6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES ...............................................................................................................15 
6.1. 
Baseline and Demographics, Physical Characteristics, and Disease History .............15 
6.1.1. 
Demographics .............................................................................................................15 
6.1.2. 
Baseline Disease Characteristics ................................................................................15 
6.1.3. 
Disease History ...........................................................................................................15 
6.1.4. 
Prior Therapy ..............................................................................................................15 
6.1.5. 
Medical History ..........................................................................................................16 
6.2. 
Disposition of Subjects ...............................................................................................16 
6.3. 
Protocol Deviations ....................................................................................................16 
6.4. 
Exposure .....................................................................................................................16 
6.5. 
Study Drug Compliance .............................................................................................17 
6.6. 
Prior and Concomitant Medication .............................................................................17 
7. 
EFFICACY .................................................................................................................18 
7.1. 
Efficacy Hypotheses ...................................................................................................18 
7.2. 
Analysis of the Primary Efficacy Parameter ..............................................................18 
7.2.1. 
Primary Efficacy Analysis ..........................................................................................18 
7.2.1.1. 
Response Criteria ........................................................................................................18 
7.2.1.2. 
Objective Response Rate and Best Response .............................................................18 
7.2.2. 
Subgroup Analyses for Primary Endpoint ..................................................................19 
7.2.3. 
Sensitivity Analyses for Primary Endpoint ................................................................19 
7.3. 
Analysis of the Secondary Efficacy Parameters .........................................................19 
7.3.1. 
Secondary Endpoints Involving Objective Response Rate ........................................19 
7.3.2. 
Progression-Free Survival ..........................................................................................19 
7.3.3. 
Duration of Response .................................................................................................20 
7.3.4. 
Disease Control Rate ..................................................................................................21 
7.3.5. 
Overall Survival ..........................................................................................................21 
7.4. 
Analysis of Other Efficacy Parameters .......................................................................21 
7.4.1. 
Largest Percentage Reduction in Sum of Diameters of Target Lesions .....................21 
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7.4.2. 
Investigator Assessed Efficacy Parameters ................................................................22 
7.4.3. 
Time to Response .......................................................................................................22 
7.4.4. 
Eastern Cooperative Oncology Group Performance Status ........................................22 
 
22 
 
22 
 
24 
7.6. 
Pharmacokinetic Analyses ..........................................................................................25 
8. 
SAFETY AND TOLERABILITY ..............................................................................25 
8.1. 
General Considerations ...............................................................................................25 
8.2. 
Adverse Events ...........................................................................................................25 
8.2.1. 
Adverse Event Definitions ..........................................................................................25 
8.2.2. 
Clinically Notable Adverse Events .............................................................................26 
8.2.3. 
Time-to-First-Event Analyses ....................................................................................26 
8.2.4. 
Adverse Event Summaries ..........................................................................................27 
8.3. 
Clinical Laboratory Tests ...........................................................................................29 
8.3.1. 
Laboratory Value Definitions .....................................................................................29 
8.3.2. 
Laboratory Value Summaries .....................................................................................29 
8.4. 
Vital Signs ..................................................................................................................30 
8.5. 
Electrocardiograms .....................................................................................................30 
9. 
INTERIM ANALYSES ..............................................................................................31 
10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................32 
10.1. 
Changes to Protocol-Defined Analyses ......................................................................32 
10.2. 
Changes to the Statistical Analysis Plan .....................................................................32 
11. 
REFERENCES ...........................................................................................................33 
APPENDIX A. PLANNED TABLES, FIGURES, AND LISTINGS ........................................34 
 
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LIST OF TABLES 
Table 1: 
Evaluation and Censoring of Progression-Free Survival ............................................20 
 
 
23 
 
 
24 
Table 4: 
Clinically Notable Adverse Events Groupings ...........................................................26 
Table 5: 
Criteria for Clinically Notable Vital Sign Abnormalities ...........................................30 
Table 6: 
Criteria for Clinically Notable Electrocardiogram Abnormalities .............................31 
Table 7: 
Statistical Analysis Plan Versions ..............................................................................32 
 
LIST OF FIGURES 
Figure 1: 
Study Design ...............................................................................................................10 
 
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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
adverse event 
BMI 
body mass index 
CI 
confidence interval 
CR 
complete response 
CRF 
case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DCR 
disease control rate 
DOR 
duration of response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
 
 
FDA 
Food and Drug Administration 
FGF 
fibroblast growth factor 
FGFR 
fibroblast growth factor receptor 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI 
National Cancer Institute 
NE 
not evaluable 
ORR 
objective response rate 
OS 
overall survival 
PD 
progressive disease 
PFS 
progression-free survival 
PK 
pharmacokinetic 
PP 
per protocol 
PR 
partial response 
 
 
 
 
QTcF 
QT interval corrected using Fridericia's formula 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SD 
stable disease 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SI 
international system of units 
TEAE 
treatment-emergent adverse event 
TNM 
TNM Classification of Malignant Tumors 
WHO 
World Health Organization 
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1. 
INTRODUCTION 
This is a Phase 2, open-label, monotherapy study of INCB054828 in subjects with 
advanced/metastatic or surgically unresectable cholangiocarcinoma with FGFR2 translocations, 
with other FGF/FGFR alterations, or who are negative for FGF/FGFR alterations.  A detailed 
description of the investigational product, target patient population, rationale for doses to be 
examined, and potential risks and benefits of treatment with INCB054828 are provided in the 
Protocol, Section 1. 
The purpose of this SAP is to provide details of the statistical analyses that have been outlined in 
the Study INCB 54828-202 Protocol. 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 54828-202 Protocol Amendment 6 dated 15 FEB 2018 and CRFs 
approved on 27 NOV 2018.  Unless superseded by an amendment, this SAP will be effective for 
all subsequent protocol amendments and eCRF versions. 
2.2. 
Study Objectives 
2.2.1. 
Primary Objective 
• To evaluate the efficacy of INCB054828 in subjects with advanced/metastatic or 
surgically unresectable cholangiocarcinoma with FGFR2 translocation who have 
failed at least 1 previous treatment. 
2.2.2. 
Secondary Objectives 
• To evaluate the efficacy of INCB054828 in subjects with advanced/metastatic or 
surgically unresectable cholangiocarcinoma within different molecular subgroups. 
• To evaluate the safety of INCB054828 in subjects with advanced/metastatic or 
surgically unresectable cholangiocarcinoma. 
• To identify and evaluate covariates that may influence the PK of INCB054828 in this 
subject population through population PK analysis.  Additionally, exposure-response 
analyses for key efficacy and safety parameters will also be considered if there is 
sufficient data available. 
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2.3. 
Study Endpoints 
2.3.1. 
Primary Endpoint 
• To determine the ORR in subjects with FGFR2 translocations based on the central 
genomics laboratory results.  Objective response rate is defined as the proportion of 
subjects who achieved a CR (disappearance of all target lesions) or a PR (≥ 30% 
decrease in the sum of the longest diameters of target lesions) based on RECIST v1.1.  
Clinical response will be determined by an independent radiological review 
committee. 
2.3.2. 
Secondary Endpoints 
• ORR in subjects with other FGF/FGFR alterations (Cohort B). 
• ORR in subjects with FGF/FGFR alterations (Cohorts A and B). 
• ORR in subjects negative for FGF/FGFR alterations (Cohort C [United States only]) 
• PFS (PFS = first dose to PD or death; all cohorts). 
• DOR (DOR = time from the date of CR or PR until PD; all cohorts). 
• DCR (DCR = CR + PR + SD; all cohorts). 
• OS (OS = first dose to death of any cause; all cohorts). 
• Safety and tolerability will be assessed by evaluating the frequency, duration and 
severity of AEs; through review of findings of physical examinations, changes in vital 
signs, and ECGs; and through clinical laboratory blood and urine sample evaluations 
(all cohorts). 
• Population PK (all cohorts). 
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3. 
STUDY DESIGN 
This is an open-label, monotherapy study of INCB054828 in subjects with advanced/metastatic 
or surgically unresectable cholangiocarcinoma with FGFR2 translocations, with other 
FGF/FGFR alterations, or who are negative for FGF/FGFR alterations.  The study will enroll 
approximately 140 subjects total:  100 subjects with FGFR2 translocations (Cohort A), 
20 subjects with other FGF/FGFR alterations (Cohort B), and 20 subjects with no FGF/FGFR 
alterations (Cohort C [United States only]). 
Subjects will receive INCB054828 13.5 mg once daily on a 2-weeks-on therapy and 1-week-off 
therapy schedule.  Full study drug administration information can be found in the Protocol, 
Section 5.2. 
Subject eligibility can be based on local genomic testing results, if available.  Confirmatory 
testing through the central genomics laboratory will be performed for all subjects. 
Previous therapies may include chemotherapeutic agents and immunotherapies, with or without 
radiotherapy.  Subjects receiving radiotherapy to target the lesion(s) must show progression of 
the target lesion prior to entry into the study. 
Genomic testing results will allow subjects to be assigned to a cohort as follows: 
• Cohort A:  FGFR2 translocations with a documented fusion partner in central 
laboratory report. 
• Cohort B:  other FGF/FGFR alterations. 
• Cohort C (United States only):  negative for FGF/FGFR alterations. 
Subjects enrolled based on a local sequencing report will be assigned to a cohort based on the 
local results.  However, final cohort assignments for statistical analysis will be based on the 
central genomic testing results. 
Treatment will start on Cycle 1 Day 1.  Subjects will undergo regular safety assessments during 
treatment, as well as regular efficacy assessments.  Subjects will be allowed to continue 
administration in 21-day cycles until documented disease progression or unacceptable toxicity is 
reported.  See Figure 1 for the study design. 
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Figure 1: 
Study Design 
 
D/C = discontinue; SF = screen fail; tx = treatment. 
3.1. 
Control of Type I Error 
Unless otherwise specified, all CIs provided will be at the 95% confidence level. 
3.2. 
Sample Size Considerations 
Approximately 100 subjects with documentation of FGFR2 translocation from the central 
genomics laboratory are planned for the final analysis of the primary endpoint of ORR.  With the 
assumed rate of 33% for the intervention, a sample size of approximately 100 subjects would 
provide > 95% probability to have a 95% CI with lower limit of > 15%, assuming 10% lost to 
follow-up.  Up to 20 subjects will be enrolled in Cohort B and Cohort C (United States only), 
respectively, which will provide > 80% chance of observing at least 4 responders in each cohort, 
if the underlying ORR is 30%. 
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4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS 
4.1. 
Scheduled Study Evaluations and Study Periods 
4.1.1. 
Day 1 
Day 1 is the date that the first dose of study drug (INCB054828) is administered to the subject. 
4.1.2. 
Study Day 
If a visit/reporting date is on or after the Day 1 date, then the study day at the visit/reporting date 
will be calculated as  
Day # = (Visit/Reporting Date –Day 1 date + 1) 
If the visit/reporting date is before the Day 1 date, then the study day at the visit/reporting date 
will be calculated as  
Day # = (Visit/Reporting Date – Day 1 date) 
A study day of -1 indicates 1 day before Day 1. 
4.1.3. 
Baseline Value 
Baseline is defined as the last nonmissing measurement obtained prior to the first administration 
of INCB054828.  When scheduled assessments and unscheduled assessments occur on the same 
day and time of the assessment or time of first dose is not available, use the following convention 
to determine baseline: 
• If both a scheduled and an unscheduled visit are available on the day of the first dose, 
and the time is missing, use the scheduled assessment as baseline. 
• If all scheduled assessments are missing on the day of the first dose, and an 
unscheduled assessment is available, use the unscheduled assessment as baseline. 
4.1.4. 
Handling of Missing and Incomplete Data 
In general, values for missing data will not be imputed unless methods for handling missing data 
are specified in this section or relevant sections. 
Partial disease/cancer diagnosis date will be handled as follows: 
• If only the day is missing, then the imputed day will be the first of the month. 
• If both the month and day are missing, then the imputed day and month will be 
01 JAN. 
• No imputation will be done if the date is completely missing. 
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For relevant efficacy endpoints, partial death date will be imputed as follows:  
• If mmyyyy for the last contact date = mmyyyy for the death date, then the death date 
will be set to the day after the last contact date. 
• If mmyyyy for the last contact date < mmyyyy for the death date, then the death date 
will be set to the first day of the death month. 
• Otherwise, the partial death date will not be imputed. 
4.1.5. 
Cycle Length and Duration 
Cycle 1 Day 1 is the day that the first dose of INCB054828 is administered.  Scheduled cycle 
length is 21 days, with first day of each cycle corresponding with the first day of INCB054828 
administration in that cycle. 
4.1.6. 
Analysis Window 
For parameters that will be summarized by visit, the nominal visit as recorded on the eCRF will 
be used.  There will be no additional analysis windowing done based on the assessment date. 
4.2. 
Variable Definitions 
The following variables will only be calculated if not reported on the eCRF. 
4.2.1. 
Age 
Subject age will be calculated as the integer part of the number of years from date of birth to the 
date of signing the informed consent form, using the following formula: 
Age = integer part of (date of informed consent – date of birth + 1) / 365.25) 
4.2.2. 
Body Mass Index 
Body mass index will be calculated as follows: 
BMI (kg/m2) = [weight (kg)] / [height (m)]2 
4.2.3. 
Prior and Concomitant Medication 
Prior medication is defined as any nonstudy medication started before the first dose of 
INCB054828. 
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Concomitant medication is defined as any nonstudy medication that is started accordingly: 
• Before the date of first administration of INCB054828 and is ongoing throughout the 
study or ends on/after the date of first study drug administration. 
• On/after the date of first administration of INCB054828 and is ongoing or ends 
during the course of study drug administration. 
A prior medication could also be classified as "both prior and concomitant medication" if the end 
date is on or after first dose of INCB054828.  In the listing, it will be indicated whether a 
medication is prior-only, concomitant-only, or both prior and concomitant medication. 
For the purposes of analysis, all medications will be considered concomitant medications unless 
the medications can unequivocally be defined as not concomitant. 
5. 
STATISTICAL METHODOLOGY 
5.1. 
General Methodology 
Unless otherwise noted, SAS software (SAS Institute Inc, Cary, NC; v9.1 or later) will be used 
for the generation of all tables, graphs, and statistical analyses.  Descriptive summaries for 
continuous variables will include, but not be limited to, the number of observations, mean, 
standard deviation, median, minimum, and maximum.  Descriptive summaries for categorical 
variables will include the number and percentage of subjects in each category. 
5.2. 
Treatment Groups 
Subjects will be summarized by cohorts, and cohort determination will be based on FGF/FGFR 
status from the central genomics laboratory. 
5.3. 
Analysis Populations 
5.3.1. 
Efficacy Evaluable Population 
The efficacy evaluable population includes all subjects who have a known FGF/FGFR alteration 
from the central genomics laboratory and who received at least 1 dose of INCB054828 and all 
subjects in the United States who have a negative FGF/FGFR alteration from the central 
genomics laboratory and who received at least 1 dose of INCB054828.  The efficacy evaluable 
population will be used for the summary of demographics, baseline characteristics, subject 
disposition, and analyses of all efficacy data. 
5.3.2. 
Per Protocol Population 
Subjects in the efficacy evaluable population who are considered to be sufficiently compliant 
with the protocol compose the PP population. 
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The following procedures will be performed to identify those subjects who are to be excluded 
from the PP population before the database freeze: 
• Clinical review of Protocol deviations. 
• Clinical review of concomitant medications as defined in Section 5.6 of the Protocol. 
• Clinical review of the dose administration and drug accountability listing. 
The determination of subjects being considered for exclusion from the PP population by the 
clinical team will be prepared and signed before database freeze. 
The PP population will be used in the supportive sensitivity analyses for efficacy endpoints. 
5.3.3. 
Safety Population 
The safety population includes all enrolled subjects who received at least 1 dose of 
INCB054828.  All safety analyses will be conducted using the safety population. 
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6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES 
Appendix A provides a list of planned tables, figures, and listings. 
6.1. 
Baseline and Demographics, Physical Characteristics, and Disease 
History 
Demographic and baseline characteristics, disease history, and prior therapy will be summarized 
for the efficacy evaluable population and the safety population and will be listed. 
6.1.1. 
Demographics 
The following demographic and baseline characteristics will be summarized for the efficacy 
evaluable population:  age, sex, race, geographic region (North America vs Western Europe vs 
rest of world), ethnicity, weight (by gender), height, and BMI. 
6.1.2. 
Baseline Disease Characteristics 
The following baseline disease characteristics will be summarized for the efficacy evaluable 
population:  ECOG performance status and baseline phosphate. 
6.1.3. 
Disease History 
Time since diagnosis, stage at diagnosis, cholangiocarcinoma location at diagnosis, current TNM 
classification, and tumor marker test results will be summarized. 
Time since diagnosis will be calculated as:  
Time since diagnosis (years) = (Day 1 date – date of diagnosis + 1) / 365.25 
6.1.4. 
Prior Therapy 
Number of subjects who received prior systemic cancer therapy, number of prior systemic cancer 
therapy regimens, number of subjects who received prior neoadjuvant therapy, number of 
subjects who received prior adjuvant therapy, as well as number of subjects who received prior 
platinum therapy, will be summarized for the efficacy evaluable population.  Regimen name, 
component drugs, start and stop dates, purpose of the regimen, best response, reason for 
discontinuation, and date of relapse/progression will be listed. 
Number of subjects who received prior radiation will be summarized for the efficacy evaluable 
population.  Radiotherapy type, body site, start and stop dates, total dose, and best response will 
be listed. 
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Number of subjects who had prior surgery or surgical procedure for the malignancies under 
study will be summarized for the efficacy evaluable population.  Date and description of the 
surgery/procedure will be listed. 
6.1.5. 
Medical History 
For subjects in the efficacy evaluable population, general medical history, as well as hepatitis 
history, will be summarized by system organ class and preferred term and will be listed.  
Preferred terms for hepatitis history include, but are not limited to the following:  hepatitis B; 
hepatitis C; viral hepatitis carrier; hepatitis non-A, non-B, non-C; and fascioliasis. 
6.2. 
Disposition of Subjects 
The number and percentage of subjects who were treated, discontinued study treatment with a 
primary reason for discontinuation, and discontinued from the study with a primary reason for 
withdrawal will be summarized for the efficacy evaluable population. 
6.3. 
Protocol Deviations 
Protocol deviations collected on the eCRF will be summarized descriptively and listed. 
6.4. 
Exposure 
For subjects in the safety population, exposure to INCB054828 will be summarized descriptively 
as the following: 
• Number of treatment cycles:  Number of cycles with a nonzero dose of 
INCB054828. 
• Duration of treatment (weeks):  (date of last dose of INCB054828 – date of first 
dose of INCB054828 + 1) / 7. 
• Number of days with INCB054828:  Number of days with a nonzero dose of 
INCB054828. 
• Average daily dose (mg/day):  Total actual INCB054828 dose taken (mg) / duration 
of treatment. 
Duration of exposure in months will be calculated based on the assumption that each month has 
30.4375 days.  The number and percentage of subjects in each duration category (< 1 month, 
1-< 3 months, 3-< 6 months, 6-< 9 months, 9-< 12 months, 12-< 15 months, 15-< 18 months, 
18-< 21 months, 21-< 24 months, > 24 months as applicable) will be summarized. 
Number of subjects without dose reduction, with at least 1 dose reduction, with only 1 dose 
reduction, as well as with more than 1 dose reduction will be summarized. 
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Number of subjects without dose interruption, with at least 1 dose interruption, with only 1 dose 
interruption, as well as with more than 1 dose interruption will be summarized. 
Final dose, defined as last nonmissing dose in the study or last nonmissing dose prior to data 
cutoff date if subject is still ongoing, will be summarized. 
6.5. 
Study Drug Compliance 
Overall compliance (%) for INCB054828 will be calculated for all subjects as: 
Compliance (%) = 100 × [total dose actually taken] / [total prescribed dose]. 
The total prescribed dose is defined as the sum of the doses prescribed by the investigator 
accounting for dose modifications. 
The total actual dose taken will be calculated based on information entered on the drug 
accountability eCRF.  If there is dispensed drug that has not been returned yet, the actual dose 
taken starting from the dispense date of the unreturned drug will be imputed by the dose taken as 
reported on the dosing eCRF. 
Compliance of INCB054828 will be summarized descriptively and listed. 
6.6. 
Prior and Concomitant Medication 
Prior medications and concomitant medications will be coded using the WHO Drug Dictionary.  
For subjects in the safety population, the number and percentage of subjects with prior and 
concomitant medications will be summarized by WHO drug class and WHO drug term.  In the 
data listing, each medication will be recorded as prior, concomitant, or both prior and 
concomitant. 
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7. 
EFFICACY 
Appendix A provides a list of planned tables, figures, and listings. 
7.1. 
Efficacy Hypotheses 
Not applicable. 
7.2. 
Analysis of the Primary Efficacy Parameter 
7.2.1. 
Primary Efficacy Analysis 
The primary endpoint of the study is ORR in subjects with FGFR2 translocations based on the 
central genomics laboratory results, defined as the proportion of subjects with best response of 
CR or PR based on review of scans by an independent centralized radiological review committee 
per RECIST v1.1 (Eisenhauer et al 2009) results.  Confirmation of CR and PR is required and 
documented in the Independent Central Review Charter.  This analysis will be based on efficacy 
evaluable population for subjects with FGFR2 translocations.  Subjects who do not have 
sufficient baseline or on-study response assessment information to be adequately assessed for 
response status will be included in the denominators in the calculation of ORR.  The 95% CI for 
ORR will be calculated using exact method for binomial distribution.   
The ORR will also be analyzed based on the PP population as a sensitivity analysis. 
7.2.1.1. 
Response Criteria 
Objective assessment of tumor status will be evaluated by an independent centralized 
radiological review committee based on RECIST v1.1, and response status will be logged into 
the eCRF. 
Response status will be recorded at each response assessment visit as CR, PR, SD, PD, or NE. 
7.2.1.2. 
Objective Response Rate and Best Response 
Subjects are considered objective responders if they have a best overall response of CR or PR at 
any postbaseline visit prior to first PD. 
In general, best overall response is the best response recorded postbaseline prior to and including 
the first PD, in the order of CR, PR, SD, PD, and NE.  A best overall response of CR or PR 
needs to be confirmed, and confirmation method is described in the Independent Central Review 
Charter.  In the case of SD, measurements must meet the SD criteria at least once after the date 
of first dose at a minimum interval of 39 days.  Subjects that fail to meet this criterion will have 
best overall response of PD if the next available assessment indicates PD or NE if there is no 
additional assessment available. 
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7.2.2. 
Subgroup Analyses for Primary Endpoint 
Subgroups will be formed based on the following subject characteristics and baseline variables 
for those subjects whose data are available: 
• Age category (< 65 years vs 65-< 75 years vs ≥75 years) 
• Sex (female vs male) 
• Region (North America vs Western Europe vs rest of world) 
• Baseline ECOG performance score (0 vs 1/2) 
• Metastatic disease present (yes vs no) 
• Lines of prior therapy (1 line vs 2 lines vs ≥ 3 lines) 
• Received previous platinum treatment (yes vs no) 
• Renal impairment grade (normal vs mild vs moderate vs severe) 
• Hepatic impairment grade (normal vs mild vs moderate vs severe) 
The primary endpoint will be summarized for subgroups and a forest plot of ORR and its 95% CI 
for each subgroup will be provided. 
7.2.3. 
Sensitivity Analyses for Primary Endpoint 
The primary endpoint will be analyzed using the PP population as a sensitivity analysis to the 
efficacy evaluable population. 
7.3. 
Analysis of the Secondary Efficacy Parameters 
7.3.1. 
Secondary Endpoints Involving Objective Response Rate 
The secondary endpoints involving ORR in this study includes: 
• ORR in subjects with other FGF/FGFR alterations (Cohort B). 
• ORR in all subjects with FGF/FGFR alterations (Cohorts A and B). 
• ORR in subjects negative for FGF/FGFR alterations (Cohort C [United States only]). 
ORR is based on review of scans by an independent centralized radiological review committee, 
and confirmation of response is required.  The second endpoints involving ORR will be analyzed 
in the same way as the primary endpoint, and the 95% CI for ORR will be calculated using exact 
method for binomial distribution. 
7.3.2. 
Progression-Free Survival 
Progression-free survival is defined as the length of time from the start of the study drug (Day 1) 
until the earlier of death or PD by RECIST v1.1 as assessed by the independent centralized 
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radiological review committee.  The date of PD will be the timepoint at which progression is first 
recorded.  Censoring for PFS will follow the algorithm outlined in Table 1, which is based on the 
FDA Guidance for Industry:  Clinical Trial Endpoints for the Approval of Cancer Drugs and 
Biologics (FDA 2015, FDA 2018) 
The number of subjects who progressed or died and the number of subjects censored will be 
summarized.  The Kaplan-Meier estimate of median PFS will be presented with its 95% CI.  The 
95% CI will be calculated using the Brookmeyer and Crowley's method (Brookmeyer and 
Crowley 1982).  The PFS analysis will be conducted for Cohorts A, B, and C, respectively. 
Progression-free survival for Cohort A will be analyzed for each subgroup as described in 
Section 7.2.2, with the exception of renal/hepatic impairment.  If there are sufficient subjects in 
each subgroup, forest plots of median PFS and its 95% CI for each subgroup will be provided. 
Table 1: 
Evaluation and Censoring of Progression-Free Survival 
Situation 
Outcome 
Date of Progression or Censoring 
No baseline tumor assessment  
Censored 
Day 1  
No adequate postbaseline response assessment  
Censored 
Day 1  
Progression documented between scheduled 
response assessments  
Progressed 
Date of first overall response of 
progressive disease  
No progression  
Censored 
Date of last adequate response assessment 
(not NE and not missing)  
Study discontinuation for undocumented 
progression  
Censored 
Date of last adequate response assessment 
(not NE and not missing)  
Study discontinuation for toxicity or other 
reason  
Censored 
Date of last adequate response assessment 
(not NE and not missing)  
New anticancer treatment started  
Censored 
Date of last adequate response assessment 
(not NE and not missing) prior to starting 
of the new anticancer treatment 
Death before first progressive disease 
assessment  
Progressed 
Date of death  
Death between adequate assessment visits  
Progressed 
Date of death  
Death or progression after more than 1 missed 
assessment  
Censored 
Date of last adequate response assessment 
(not NE and not missing)  
NE = not evaluable. 
7.3.3. 
Duration of Response 
For objective responders, DOR is the time from the first overall response contributing to an 
objective response as assessed by an independent centralized radiological review committee per 
RECIST v1.1, to the earlier of death or first overall response of PD occurring after the first 
overall response contributing to the objective response.  Censoring of DOR will follow the same 
algorithm as the censoring of PFS (see Section 7.3.2). 
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The total number of responders, the number of subjects who progressed or died, and the number 
of subjects censored will be summarized.  The Kaplan-Meier estimate of median DOR will be 
presented with its 95% CI.  The 95% CI for DOR will be calculated using the Brookmeyer and 
Crowley's method (Brookmeyer and Crowley 1982).  The DOR analysis will be conducted for 
Cohorts A, B, and C, respectively. 
Subgroup analysis of DOR for Cohort A will be conducted for renal impairment grade and for 
hepatic impairment grade if there are sufficient responders in each subgroup. 
7.3.4. 
Disease Control Rate 
Disease control rate is defined as the proportion of subjects with best response of CR, PR, or SD 
based on review of scans by an independent centralized radiological review committee per 
RECIST v1.1.  Confirmation of CR and PR is required and documented in the Independent 
Central Review Charter.  This analysis will be based on efficacy evaluable population for 
subjects in Cohorts A, B, and C, respectively.  Subjects who do not have sufficient baseline or 
on-study response assessment information to be adequately assessed for response status will be 
included in the denominators in the calculation of DCR.  The 95% CI for DCR will be calculated 
using exact method for binomial distribution. 
7.3.5. 
Overall Survival 
Overall survival is defined as the length of time from the start of the study drug (Day 1) until the 
date of death due to any cause.  Date of death will be determined using the Death Report and the 
Survival Follow-Up eCRFs.  Subjects who are lost to follow-up or still alive at the time of 
analysis will be right-censored at the earlier of the date the subject was last known alive and the 
clinical data cut-off date for the analysis.  The last known alive date is defined as the later of the 
last study visit and the date the subject was last known alive from the Survival Follow-Up and 
Subject Status eCRFs. 
The number of subjects who died and the number of subjects censored will be summarized.  The 
Kaplan-Meier estimate of median OS will be presented with its 95% CI.  The 95% CI for OS 
will be calculated using the Brookmeyer and Crowley's method (Brookmeyer and 
Crowley 1982).  The OS analysis will be conducted for Cohorts A, B, and C, respectively. 
7.4. 
Analysis of Other Efficacy Parameters 
7.4.1. 
Largest Percentage Reduction in Sum of Diameters of Target Lesions 
For subjects with measurable lesions at baseline, target lesion sizes will be measured by sum of 
diameters.  The best percent change from baseline, defined as the largest decrease in target lesion 
size during the study, will also be summarized, and a waterfall plot of best percent change will 
be generated. 
Target lesions considered "too small to measure" will be assigned a default value of 5 mm for 
purposes of this analysis.  Likewise, target lesions identified as "not present" at postbaseline 
assessments will be assigned 0 mm for this analysis.  In the event that a target lesion is 
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unaccounted for in a particular postbaseline timepoint (ie, the assessment is missing or NE), then 
the overall sum of diameters for target lesions will not be evaluable for that postbaseline 
timepoint. 
7.4.2. 
Investigator Assessed Efficacy Parameters 
Objective response rate, PFS, DOR, and DCR based on review of scans by investigator per 
RECIST v1.1 will be analyzed in a similar fashion as those parameters assessed by an 
independent centralized radiological review committee.  Confirmation of CR and PR is not 
required. 
Objective response rate, DOR, and DCR assessed by an independent centralized radiological 
review committee per RECIST v1.1 without requirement of CR and PR confirmation will also be 
analyzed. 
7.4.3. 
Time to Response 
Time-to-onset of response is defined as the time from the start of the study drug (Day 1) until the 
date of first confirmed CR or PR as assessed by the independent centralized radiological review 
committee per RECIST v1.1.  The date of first confirmed CR or PR is the date when the criteria 
for CR or PR is first met and the CR or PR is confirmed at a subsequent timepoint. 
For responders, time-to-onset of response will be summarized. 
7.4.4. 
Eastern Cooperative Oncology Group Performance Status 
Eastern Cooperative Oncology Group performance status at scheduled assessment times will be 
summarized. 
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7.6. 
Pharmacokinetic Analyses 
The data will be analyzed by standard population PK methods using appropriate software 
(eg, NONMEM®).  An attempt will be made to evaluate the effect of demographic characteristics 
and baseline characteristics (eg, age, weight, sex, race, renal function, FGF/FGFR alteration 
status) on the population PK profile.  Additionally, exposure-response analyses for key efficacy 
and safety parameters may also be considered if there are sufficient data available. 
8. 
SAFETY AND TOLERABILITY 
Appendix A provides a list of planned tables, figures, and listings. 
8.1. 
General Considerations 
The analyses for this section will be provided for the safety population.  Summary tables may be 
replaced with listings when appropriate.  For instance, an AE frequency table may be replaced 
with a listing if it only contains a few unique preferred terms reported on relatively few subjects. 
8.2. 
Adverse Events 
8.2.1. 
Adverse Event Definitions 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after 
first dose of study drug and within 30 days of last dose of study drug.  Analysis of AEs (as 
discussed below) will be limited to TEAEs, but data listings will include all AEs regardless of 
their timing to study drug administration. 
Adverse events will be tabulated by MedDRA preferred term and system organ class.  Severity 
of AEs will be described and graded using the NCI CTCAE v4.03.  The CTCAE v4.03 reporting 
guidelines and grading details are available on the Cancer Therapy Evaluation Program website.  
A grading (severity) scale is provided for each AE term.  If the toxicity is not included in the 
CTCAE v4.03 criteria, it will be rated on a scale of 1 to 4 as follows:  1 = mild, 2 = moderate, 
3 = severe, and 4 = life-threatening.  All toxicities will be graded based on the worst level 
reached, not the level they may have reached if they had not been treated.  When the intensity of 
an AE changes over time for a reporting period (eg, between visits), each change in intensity will 
be reported as an AE until the event resolves. 
The subset of AEs considered by the investigator to be related to study drug will be considered to 
be treatment-related AEs.  The incidence of AEs and treatment-related AEs will be tabulated.  
Serious adverse events will also be tabulated. 
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Any missing onset date, causality, or severity must be queried for resolution.  Unsolved missing 
values will be handled according to the following rules: 
• An unsolved missing causality will be considered treatment-related. 
• An unsolved missing severity will be identified as an unknown severity. 
For purposes of analysis, all AEs will be considered TEAEs unless they can unequivocally be 
defined as not treatment-emergent. 
8.2.2. 
Clinically Notable Adverse Events 
Specific groupings of clinically notable AEs will be considered and the number of subjects with 
at least 1 event within each grouping will be reported.  Such groups consist of AEs for which 
there is a specific clinical interest in connection with the study drug or AEs that are similar in 
nature (although not identical).  The groups are defined as per Table 4.  All clinically notable 
AEs are defined through reviewing preferred term according to the current MedDRA v21.1. 
Table 4: 
Clinically Notable Adverse Events Groupings 
Categories 
Preferred Terms 
Serous retinal detachment 
Serous retinal detachment, detachment of macular retinal 
pigment epithelium, detachment of retinal pigment 
epithelium, retinal detachment, subretinal fluid, retinal 
oedema, chorioretinopathy, retinal pigment epitheliopathy,  
chorioretinal disorder, retinopathy 
Nail toxicity 
Nail toxicity, nail bed tenderness, nail bed disorder, nail 
bed bleeding, nail disorder, nail discolouration, nail 
discomfort, nail dystrophy, nail hypertrophy, nail ridging, 
nail infection, onychalgia, onychoclasis, onycholysis, 
onychomadesis, onychomycosis, paronychia, fungal 
paronychia 
Hyperphosphatemia 
Hyperphosphataemia, blood phosphorus increased 
Hypophosphatemia 
Hypophosphataemia, blood phosphorus decreased 
8.2.3. 
Time-to-First-Event Analyses 
For clinically notable AEs identified in Table 4, time-to-first event analyses will be performed. 
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Time-to-first occurrence of an AE is defined as the time from start of study drug to the date of 
first occurrence of an AE, that is, time in days is calculated as (start date of first occurrence 
of AE) – (date of first dose of study drug) + 1.  A subject will be censored for time-to-onset if: 
• The subject dies with no event. 
• The subject receives a new anticancer therapy with no event or before the event has 
occurred. 
• The subject discontinues from the study treatment with no event (up to 30 days after 
study treatment discontinuation). 
• The subject is still ongoing at the cutoff with no event. 
In the absence of an event, the censoring date applied will be the earliest from the following 
dates:  date of last dose + 30 days, analysis cutoff, new anticancer therapy start, and death. 
The analyses will comprise the following: 
• Time-to-onset of first new TEAE (any grade) 
• Time-to-onset of first new TEAE of Grade 3 or higher 
8.2.4. 
Adverse Event Summaries 
An overall summary of AEs by cohort will include: 
• Number (%) of subjects reporting any TEAEs 
• Number (%) of subjects reporting any SAEs 
• Number (%) of subjects reporting any Grade 3 or higher TEAEs 
• Number (%) of subjects reporting any TEAEs related to INCB054828 
• Number (%) of subjects who temporarily interrupted INCB054828 because of TEAEs 
• Number (%) of subjects who permanently discontinued INCB054828 because of 
TEAEs 
• Number (%) of subjects with INCB054828 dose reductions because of TEAEs 
• Number (%) of subjects who had a fatal TEAE 
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The following summaries for each cohort will be produced by MedDRA term (if ≤ 10 subjects 
appear in a table, a listing may be appropriate): 
• Summary of TEAEs by system organ class and preferred term 
• Summary of TEAEs by preferred term in decreasing order of frequency 
• Summary of TEAEs by system organ class, preferred term, and maximum severity 
• Summary of Grade 3 or higher TEAEs by system organ class and preferred term 
• Summary of Grade 3 or higher TEAEs by preferred term in decreasing order of 
frequency 
• Summary of treatment-related TEAEs by system organ class and preferred term 
• Summary of treatment-related TEAEs by preferred term in decreasing order of 
frequency 
• Summary of Grade 3 or higher treatment-related AEs by system organ class and 
preferred term 
• Summary of TEAEs with a fatal outcome by system organ class and preferred term 
• Summary of serious TEAEs by system organ class and preferred term 
• Summary of treatment-emergent SAEs by preferred term in decreasing order of 
frequency 
• Summary of treatment-related serious TEAEs by system organ class and preferred 
term 
• Summary of TEAEs leading to dose reduction by system organ class and preferred 
term 
• Summary of TEAEs leading to dose interruption by system organ class and preferred 
term 
• Summary of TEAEs leading to discontinuation of study drug by system organ class 
and preferred term 
• Summary of treatment-emergent non-SAEs by system organ class and preferred term 
• Summary of TEAEs and Grade 3 or higher AEs by preferred term in decreasing order 
of frequency 
• Summary of clinically notable TEAEs by category and preferred term 
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• Summary of Grade 3 or higher clinically notable TEAEs by category and preferred 
term 
• Summary of serious clinically notable TEAEs by category and preferred term 
• Summary of clinically notable TEAEs leading to dose reduction by category and 
preferred term 
• Summary of clinically notable TEAEs leading to dose interruption by category and 
preferred term 
• Summary of clinically notable TEAEs leading to discontinuation of study drug by 
category and preferred term 
• Summary of clinically notable TEAEs by category and preferred term:  life-table 
method 
• Summary of Grade 3 or higher clinically notable TEAEs by category and preferred 
term:  life-table method 
8.3. 
Clinical Laboratory Tests 
8.3.1. 
Laboratory Value Definitions 
For numeric laboratory results, the change and percentage change from baseline will be 
calculated.  Baseline will be determined according to Section 4.1.3.  If there are multiple values 
that meet the criteria for baseline, the value from the central laboratory has priority over the 
value from the local laboratory.  Thereafter, additional rules may be provided after consultation 
with the medical monitor to delineate which value will be defined as baseline. 
Laboratory test values outside of the normal range will be assessed for severity based on CTCAE 
grade or similar criteria where clinical intervention is required for CTCAE grading. 
8.3.2. 
Laboratory Value Summaries 
All test results and associated normal ranges from central laboratories will be reported in 
SI units.  All tests with numeric values will have a unique unit per test.  Any laboratory test 
results and associated normal ranges from local laboratories will be converted to SI units. 
For numeric laboratory values, baseline value, postbaseline value, change from baseline, and 
percent change from baseline will be summarized by visit.  In addition, mean change from 
baseline will be plotted over time for selected laboratory parameters, including phosphate, 
calcium, sodium, 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, and parathyroid hormone.  
For the laboratory parameters that have CTCAE grading, shift tables will also be presented 
showing change in CTCAE severity grade from baseline to worst grade postbaseline.  The 
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denominator for the percentage calculation will be the number of subjects in the baseline 
category. 
Categorical laboratory data will be tabulated by visit at baseline and postbaseline visits where 
appropriate. 
8.4. 
Vital Signs 
Values at each scheduled visit, change, and percent change from baseline for vital signs, 
including systolic blood pressure, diastolic blood pressure, pulse, respiratory rate, weight, and 
body temperature, will be summarized descriptively. 
Criteria for clinically notable vital sign abnormalities are defined in Table 5.  The abnormal 
values for subjects exhibiting clinically notable vital sign abnormalities will be listed.  Alert vital 
signs are defined as an absolute value outside of the defined range and percentage change from 
baseline greater than 25%.  The abnormal values for subjects exhibiting alert vital sign 
abnormalities will also be listed. 
Table 5: 
Criteria for Clinically Notable Vital Sign Abnormalities 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
> 155 mmHg 
< 85 mmHg 
Diastolic blood pressure 
> 100 mmHg 
< 40 mmHg 
Pulse 
> 100 bpm 
< 45 bpm 
Temperature 
> 38°C 
< 35.5°C 
Respiratory rate 
> 24 breaths/min 
< 8 breaths/min 
8.5. 
Electrocardiograms 
Twelve-lead ECGs including PR, QRS, QT, and QTcF intervals, as well as heart rate, will be 
obtained for each subject during the study.  Values at each scheduled visit, change, and percent 
change from baseline will be summarized for each ECG parameter.  Change and percent change 
from baseline will be calculated using the average of all nonmissing values before the first dose 
of INCB054828 as the baseline value. 
Criteria for clinically notable ECG abnormalities are defined in Table 6.  The abnormal values 
for subjects exhibiting clinically notable ECG abnormalities will be listed with study visit.  Alert 
ECG values are defined as both the absolute value outside the defined range and the percentage 
change greater than 25% (QRS 30%).  The abnormal values for subjects exhibiting alert ECG 
abnormalities will be identified and listed. 
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Table 6: 
Criteria for Clinically Notable Electrocardiogram Abnormalities 
Parameter 
High Threshold 
Low Threshold 
QTcF 
> 460 ms 
< 295 ms 
PR 
> 220 ms 
< 75 ms 
QRS 
> 120 ms 
< 50 ms 
QT 
> 500 ms 
< 300 ms 
9. 
INTERIM ANALYSES 
For Cohort A (FGFR2 translocation), a futility analysis will be performed when approximately 
25 subjects are enrolled into the cohort and have at least 1 tumor assessment or have permanently 
discontinued study treatment.  Cohort A can be stopped for futility if 2 or fewer responders are 
observed, for which there is less than a 10% probability of claiming ORR > 15% at final analysis 
based on a 60-subject cohort, as initially planned before Amendment 5.  This rule is just a 
guidance and is nonbinding. 
Cohorts B (other FGF/FGFR alterations) and C (United States only; negative for FGF/FGFR 
alterations) can be stopped if 1 or less responders are observed within the first 10 subjects 
enrolled into the cohort who have at least 2 cycles of data.  This rule is just a guidance and is 
nonbinding. 
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10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN 
All versions of the SAP are listed in Table 7. 
Table 7: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
12 JUN 2017 
Amendment 1 
15 APR 2019 
10.1. 
Changes to Protocol-Defined Analyses 
Not applicable. 
10.2. 
Changes to the Statistical Analysis Plan 
The original SAP has been updated to incorporate the Protocol Amendments 5 and 6 updates.  
Specific changes are outlined below: 
• Subgroup analyses have been added for the primary endpoint (ORR in Cohort A) and the 
secondary endpoint (PFS in Cohort A). 
• Renal and hepatic subgroup analyses for ORR and DOR have been added. 
• Average daily dose has been updated to use duration of treatment as the denominator. 
• Move analysis of largest percentage reduction in sum of diameters of target lesions from 
secondary efficacy parameters section to other efficacy parameters section 
• Time-to-response analysis has been added. 
• Investigator assessed efficacy parameters have been added as other efficacy analyses. 
• Summary of weight has been moved from efficacy section to vital sign section. 
• Clinical notable adverse events and time to first occurrence of clinical notable adverse 
events have been added. 
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11. 
REFERENCES 
Brookmeyer R, Crowley J. A confidence interval for the median survival time. Biometrics 
1982;38:29-41. 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors: 
revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-247. 
Food and Drug Administration (FDA). Guidance for Industry: Clinical Trial Endpoints for the 
Approval of Non-Small Cell Lung Cancer Drugs and Biologics. 2015. 
https://www.fda.gov/downloads/drugs/guidances/ucm259421.pdf. Accessed April 12, 2019. 
Food and Drug Administration (FDA). Guidance for Industry: Clinical Trial Endpoints for the 
Approval of Cancer Drugs and Biologics. 2018. 
https://www.fda.gov/downloads/Drugs/Guidances/ucm071590.pdf. Accessed April 12, 2019. 
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APPENDIX A. PLANNED TABLES, FIGURES, AND LISTINGS 
This appendix provides a list of the planned tables, figures, and listings for the Clinical Study 
Report.  Standard tables will follow the conventions in the Standard Safety Tables initial version.  
Shells are provided for nonstandard tables in a separate document.  In-text tables are identical in 
structure and content as appendix tables, but follow a Rich Text Format. 
The lists of tables, figures, and listings are to be used as guidelines.  Modifications of the lists 
that do not otherwise affect the nature of the analysis will not warrant an amendment to the SAP.  
Each table will display Cohorts A, B, and C unless otherwise noted in the title. 
Tables 
Table No. 
Title 
Population 
Baseline and Demographic Characteristics 
1.1.1 
Analysis Populations 
All Enrolled 
1.1.2 
Summary of Subject Disposition 
Efficacy, Safety 
1.1.3 
Summary of Number of Subjects Enrolled by Country and Site 
Efficacy, Safety 
1.1.4 
Summary of Protocol Deviations 
Efficacy, Safety 
1.1.5 
Summary of Cohorts 
All Enrolled 
1.2.1 
Summary of Demographics and Baseline Characteristics 
Efficacy, Safety 
1.2.2 
Summary of Disease History 
Efficacy, Safety 
1.2.3 
Summary of Prior Cancer Therapy 
Efficacy, Safety 
1.3.1 
Summary of Medical History 
Efficacy, Safety 
1.3.2 
Summary of Hepatitis History 
Efficacy, Safety 
1.4.1 
Summary of Prior Medications 
Efficacy, Safety 
1.4.2 
Summary of Concomitant Medications 
Efficacy, Safety 
Efficacy 
2.1.1 
Summary of Best Response and Objective Response Rate – Cohort A 
Efficacy 
2.1.2 
Summary of Best Response and Objective Response Rate – Cohort A 
Per Protocol 
2.1.3 
Subgroup Analysis of Best Response and Objective Response Rate – Cohort A  
Efficacy 
2.2.1 
Summary of Best Response and Objective Response Rate – Cohort B 
Efficacy 
2.2.2 
Summary of Best Response and Objective Response Rate – Cohorts A and B 
Efficacy 
2.2.3 
Summary of Best Response and Objective Response Rate – Cohort C 
Efficacy 
2.2.4 
Summary of Duration of Response 
Efficacy 
2.2.5 
Subgroup Analysis of Duration of Response – Cohort A 
Efficacy 
2.2.6 
Summary of Disease Control Rate  
Efficacy 
2.2.7 
Summary of Progression-Free Survival 
Efficacy 
2.2.8 
Subgroup Analysis of Progression-Free Survival – Cohort A 
Efficacy 
2.2.8 
Summary of Overall Survival 
Efficacy 
2.3.1 
Summary of Best Change in Target Lesion Size (Sum of Diameters, mm) 
Efficacy 
2.3.2 
Summary of Time to Response 
Efficacy 
2.3.3 
Summary of ECOG Performance Status 
Efficacy 
 
 
 
 
 
 
CONFIDENTIAL 


Incyte Corporation 
Page 35 of 38 
INCB 54828-202 SAP Amendment 1 
15 APR 2019 
Table No. 
Title 
Population 
Safety 
3.1.1 
Summary of Study Drug Exposure 
Safety 
3.1.2 
Summary of Study Drug Compliance 
Safety 
3.1.3 
Summary of Study Drug Dose Modification and Final Dose 
Safety 
3.2.1 
Overall Summary of Treatment-Emergent Adverse Events 
Safety 
3.2.2 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class and Preferred Term 
Safety 
3.2.3 
Summary of Treatment-Emergent Adverse Events by MedDRA Preferred Term 
in Decreasing Order of Frequency 
Safety 
3.2.4 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class, Preferred Term, and Maximum Severity 
Safety 
3.2.5 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term 
Safety 
3.2.6 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency 
Safety 
3.2.7 
Summary of Treatment-Related Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term 
Safety 
3.2.8 
Summary of Treatment-Related Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency 
Safety 
3.2.9 
Summary of Grade 3or Higher Treatment-Related Adverse Events by MedDRA 
System Organ Class and Preferred Term 
Safety 
3.2.10 
Summary of Treatment-Emergent Adverse Events With a Fatal Outcome by 
MedDRA System Organ Class and Preferred Term  
Safety 
3.2.11 
Summary of Treatment-Emergent Serious Adverse Events by MedDRA System 
Organ Class and Preferred Term  
Safety 
3.2.12 
Summary of Treatment-Emergent Serious Adverse Events by MedDRA 
Preferred Term in Decreasing Order of Frequency 
Safety 
3.2.13 
Summary of Treatment-Related Serious Adverse Events by MedDRA System 
Organ Class and Preferred Term  
Safety 
3.2.14 
Summary of Treatment-Emergent Adverse Events Leading to INCB054828 Dose 
Reduction by MedDRA System Organ Class and Preferred Term 
Safety 
3.2.15 
Summary of Treatment-Emergent Adverse Events Leading to INCB054828 Dose 
Interruption by MedDRA System Organ Class and Preferred Term 
Safety 
3.2.16 
Summary of Treatment-Emergent Adverse Events Leading to Discontinuation of 
INCB054828 by MedDRA System Organ Class and Preferred Term  
Safety 
3.2.17 
Summary of Treatment-Emergent Non-Serious Adverse Events by MedDRA 
System Organ Class and Preferred Term 
Safety 
3.2.18 
Summary of Treatment-Emergent Adverse Events and Grade 3 or Higher 
Adverse Events by MedDRA Preferred Term in Decreasing Order of Frequency 
Safety 
3.2.19 
Summary of Sponsor-Defined Clinically Notable Treatment-Emergent Adverse 
Events by Category and Preferred Term  
Safety 
3.2.20 
Summary of Grade 3 or Higher Sponsor-Defined Clinically Notable Treatment-
Emergent Adverse Events by Category and Preferred Term 
Safety 
3.2.21 
Summary of Serious Sponsor-Defined Clinically Notable Treatment-Emergent 
Adverse Events by Category and Preferred Term  
Safety 
CONFIDENTIAL 


Incyte Corporation 
Page 36 of 38 
INCB 54828-202 SAP Amendment 1 
15 APR 2019 
Table No. 
Title 
Population 
3.2.22 
Summary of Sponsor-Defined Clinically Notable Treatment-Emergent Adverse 
Events Leading to Dose Reduction by Category and Preferred Term  
Safety 
3.2.23 
Summary of Sponsor-Defined Clinically Notable Treatment-Emergent Adverse 
Events Leading to Dose Interruption by Category and Preferred Term  
Safety 
3.2.24 
Summary of Sponsor-Defined Clinically Notable Treatment-Emergent Adverse 
Events Leading to Discontinuation of Study Drug by Category and Preferred 
Term  
Safety 
3.2.25 
Summary of Sponsor-Defined Clinically Notable Treatment-Emergent Adverse 
Events by Category and Preferred Term:  Life-Table Method 
Safety 
3.2.26 
Summary of Grade 3 or Higher Sponsor-Defined Clinically Notable Treatment-
Emergent Adverse Events by Category and Preferred Term:  Life-Table Method 
Safety 
Laboratory 
3.3.1 
Summary of Laboratory Values – Hematology 
Safety 
3.3.2 
Shift Summary of Hematology Values in CTC Grade – To the Worst Abnormal 
Value 
Safety 
3.3.3 
Summary of Treatment-Emergent Worsening of Laboratory Abnormalities – 
Hematology 
Safety 
3.3.4 
Summary of Laboratory Values – Chemistry 
Safety 
3.3.5 
Shift Summary of Chemistry Values in CTC Grade – To the Worst Abnormal 
Value 
Safety 
3.3.6 
Summary of Treatment-Emergent Worsening of Laboratory Abnormalities – 
Chemistry 
Safety 
3.3.7 
Summary of Laboratory Values – Coagulation 
Safety 
3.3.8 
Shift Summary of Coagulation Values in CTC Grade – To the Worst Abnormal 
Value 
Safety 
3.3.9 
Summary of Treatment-Emergent Worsening of Laboratory Abnormalities – 
Coagulation 
Safety 
3.3.10 
Summary of Laboratory Values – Urinalysis 
Safety 
Vital Signs 
3.4.1 
Summary of Systolic Blood Pressure 
Safety 
3.4.2 
Summary of Diastolic Blood Pressure 
Safety 
3.4.3 
Summary of Pulse 
Safety 
3.4.4 
Summary of Body Temperature 
Safety 
3.4.5 
Summary of Respiratory Rate 
Safety 
3.4.6 
Summary of Body Weight 
Safety 
ECG 
3.5.1 
Summary of PR Interval (ms) From 12-Lead ECG 
Safety 
3.5.2 
Summary of QRS Interval (ms) From 12-Lead ECG 
Safety 
3.5.3 
Summary of QT Interval (ms) From 12-Lead ECG 
Safety 
3.5.4 
Summary of QTcF Interval (ms) From 12-Lead ECG 
Safety 
3.5.5 
Summary of Heart Rate (bpm) From 12-Lead ECG 
Safety 
3.5.6 
Summary of Outliers of QT and QTcF Interval Values From 12-Lead ECG 
Safety 
3.5.7 
Summary of Clinically Significant ECG Abnormalities 
Safety 
CONFIDENTIAL 


Incyte Corporation 
Page 37 of 38 
INCB 54828-202 SAP Amendment 1 
15 APR 2019 
Figures 
Figure No. 
Title 
4.1 
Forest Plot of Objective Response Rate (Efficacy) 
4.2.1 
Kaplan-Meier Estimates of Progression-Free Survival (Efficacy)  
4.2.2 
Kaplan-Meier Estimates of Duration of Response (Efficacy) 
4.2.3 
Kaplan-Meier Estimates of Overall Survival (Efficacy) 
4.3.1 
Waterfall Plot of Best Percent Change of Target Lesion Size From Baseline (Efficacy) 
4.3.2 
Swimmer Plot of Duration of Treatment (Efficacy) 
4.3.3 
Forest Plot of Progression-Free Survival (Efficacy) 
4.3.4 
Forest Plot of Duration of Response (Efficacy) 
4.5 
Kaplan-Meier Estimates of Time to Adverse Event (Safety) 
4.6 
Line Graph of Mean Change From Baseline for Selected Laboratory Values (Safety) 
Listings 
Listing No. 
Title 
2.1.1 
Analysis Population 
2.1.2 
Subject Enrollment and Disposition Status 
2.1.3 
Subject Inclusion and Exclusion Criteria Violations 
2.2.1 
Protocol Deviations 
2.4.1 
Demographic and Baseline Characteristics 
2.4.2 
Oncology Disease History 
2.4.3 
Prior Systemic Therapy 
2.4.4 
Prior Surgery or Surgical Procedure 
2.4.5 
Prior Radiation Treatment 
2.4.6 
Post Therapy 
2.4.7 
Medical History 
2.4.8 
Hepatitis History 
2.4.9 
Prior and Concomitant Medication 
2.4.10 
FGF/FGFR Alterations 
2.5 
Study Drug Compliance 
2.6.1 
Best Overall Response, Duration of Response, Progression-Free Survival, and Overall Survival  
2.6.2 
Investigator-Reported Assessment by RECIST v1.1 
2.6.3 
Response Assessment:  Target Lesions 
2.6.4 
Response Assessment:  Non-target Lesions 
2.6.5 
Response Assessment:  New Lesions 
2.6.6 
Duration of Treatment, Best Overall Response, and Duration of Response 
2.6.7 
Tumor Tissue 
2.6.8 
ECOG Performance Status 
 
 
 
 
2.7.1 
Study Drug Administration 
2.7.2 
Adverse Events 
2.7.3 
INCB054828 Treatment-Related Adverse Events 
2.7.4 
Adverse Events Leading to Interruption, Reduction, or Discontinuation of INCB054828 
2.7.5 
Serious Adverse Events 
CONFIDENTIAL 


Incyte Corporation 
Page 38 of 38 
INCB 54828-202 SAP Amendment 1 
15 APR 2019 
Listing No. 
Title 
2.7.6 
Adverse Events Leading to Death 
2.7.8 
Adverse Events Leading to Discontinuation of INCB054828 
2.7.9 
Sponsor-Defined Clinically Notable Adverse Events 
2.8.1.1 
Clinical Laboratory Values - Hematology 
2.8.1.2 
Clinical Laboratory Values - Chemistry 
2.8.1.3 
Clinical Laboratory Values - Coagulation 
2.8.2.1 
Abnormal Clinical Laboratory Values - Hematology 
2.8.2.2 
Abnormal Clinical Laboratory Values - Chemistry 
2.8.2.3 
Abnormal Clinical Laboratory Values - Coagulation 
2.9.1 
Vital Signs 
2.9.2 
Abnormal Vital Sign Values 
2.9.3 
Alert Vital Sign Values 
2.10.1 
12-Lead ECG Values 
2.10.2 
Abnormal 12-Lead ECG Values 
2.10.3 
Alert 12-Lead ECG Values 
2.11.1 
Eye Examinations 
 
CONFIDENTIAL 


Signature Manifest
Document Number: IC-STS-SAP-0141
Revision: 0
Title: INCB 54828-202 SAP Amendment 1
All dates and times are in Eastern Standard Time.
APPROVE: 54828-202 SAP Amendment 1
Approval and Release
Name/Signature
Title
Date
Meaning/Reason
15 Apr 2019, 02:12:18 PM
Approved
15 Apr 2019, 02:50:47 PM
Approved
15 Apr 2019, 03:00:47 PM
Approved
15 Apr 2019, 03:18:58 PM
Approved