Clinical trial NCT05253807
Conditions: Non-Small Cell Lung Cancer (NSCLC)
Keywords: Advanced Non-Small Cell Lung Cancer (NSCLC) fibroblast growth factor receptor (FGFR) FGFR1-3 mutations FGFR1-3 fusions FGFR1-3 rearrangements squamous NSCLC nonsquamous NSCLC relapsed or refractory
Sponsor: Incyte Corporation
Start date: 2022-04-29; Completion date: 2023-08-16
Enrollment: 8 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is an open-label, single arm study to study the safety, efficacy and tolerability of Pemigatinib when used on participants with squamous or nonsquamous NSCLC with a documented FGFR1-3 mutations or fusions/rearrangement who have progressed on prior therapies and have no available standard treatment options

Detailed description:

Arms: arm 1: Participants with squamous NSCLC with known or likely FGFR1-3 driver mutations outside the kinase domain or fusions/rearrangements will receive intermittent dosing. arm 2: Participants with non-squamous NSCLC with known or likely FGFR1-3 driver mutations outside the kinase domain or fusions/rearrangements will receive intermittent dosing.
Interventions: intervention 1: Pemigatinib
Intervention descriptions: intervention 1: 13.5 mg tablet

Protocol documents:
Prot_000.pdf: 
Official Title: A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of 
Pemigatinib in Participants With Advanced Non–Small Cell Lung Cancer With an FGFR Alteration Who 
Progressed on Previous Therapy (FIGHT-210)
NCT Number: NCT05253807
Document Date: Clinical Study Protocol Amendment 1: 08-Dec-2021


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Clinical Study Protocol 
TITLE PAGE 
INCB 54828-210 
A Phase 2, Open-Label, Single-Arm, Multicenter Study to 
Evaluate the Efficacy and Safety of Pemigatinib in Participants 
With Advanced Non–Small Cell Lung Cancer With an FGFR 
Alteration Who Progressed on Previous Therapy (FIGHT-210) 
Product: 
Pemigatinib (INCB054828) 
IND Number: 
158,139 
EudraCT Number: 
2021‐004934‐12 
Phase of Study: 
2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, Delaware, USA 19803 
Original Protocol: 
14 OCT 2021 
Amendment 1: 
08 DEC 2021 
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, applicable Good Clinical Practices, and applicable laws 
and country-specific regulations in which the study is being conducted. 
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 prior 
written consent. 


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INVESTIGATOR'S AGREEMENT 
I have read the INCB 54828-210 Protocol Amendment 1 (dated 08 DEC 2021) 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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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
INVESTIGATOR'S AGREEMENT ................................................................................................2 
TABLE OF CONTENTS .................................................................................................................3 
LIST OF ABBREVIATIONS ..........................................................................................................8 
1. 
PROTOCOL SUMMARY ..........................................................................................11 
2. 
INTRODUCTION ......................................................................................................16 
2.1. 
Background .................................................................................................................16 
2.1.1. 
Fibroblast Growth Factor Receptor Inhibition in Oncology .......................................16 
2.1.2. 
Non–Small Cell Lung Cancer .....................................................................................17 
2.2. 
Study Rationale ...........................................................................................................18 
2.2.1. 
Scientific Rationale for Study Design ........................................................................18 
2.2.2. 
Justification for Dose ..................................................................................................19 
2.3. 
Benefit/Risk Assessment ............................................................................................19 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................20 
4. 
STUDY DESIGN .......................................................................................................22 
4.1. 
Overall Design ............................................................................................................22 
4.2. 
Overall Study Duration ...............................................................................................22 
4.3. 
Study Termination ......................................................................................................23 
5. 
STUDY POPULATION .............................................................................................24 
5.1. 
Inclusion Criteria ........................................................................................................24 
5.2. 
Exclusion Criteria .......................................................................................................25 
5.3. 
Lifestyle Considerations .............................................................................................27 
5.4. 
Screen Failures ............................................................................................................27 
5.5. 
Replacement of Participants .......................................................................................28 
6. 
STUDY TREATMENT ..............................................................................................28 
6.1. 
Study Treatment Administered ...................................................................................28 
6.2. 
Preparation, Handling, and Accountability ................................................................28 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................29 
6.4. 
Study Treatment Compliance .....................................................................................29 
6.5. 
Dose Modifications .....................................................................................................30 
6.5.1. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study 
Drug ............................................................................................................................30 


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6.5.2. 
Management of Hyperphosphatemia ..........................................................................32 
6.5.3. 
Criteria for Permanent Discontinuation of Study Drug ..............................................33 
6.6. 
Concomitant Medications and Procedures .................................................................33 
6.6.1. 
Restricted Medications and Procedures ......................................................................33 
6.6.2. 
Prohibited Medications and Procedures .....................................................................34 
6.7. 
Treatment After the End of the Study .........................................................................34 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
WITHDRAWAL ........................................................................................................35 
7.1. 
Discontinuation of Study Treatment ...........................................................................35 
7.1.1. 
Reasons for Discontinuation .......................................................................................35 
7.1.2. 
Discontinuation Procedures ........................................................................................35 
7.2. 
Participant Withdrawal From the Study .....................................................................36 
7.3. 
Lost to Follow-Up.......................................................................................................36 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................37 
8.1. 
Administrative and General Procedures .....................................................................37 
8.1.1. 
Informed Consent Process ..........................................................................................37 
8.1.2. 
Screening Procedures ..................................................................................................38 
8.1.3. 
Interactive Response Technology Procedure ..............................................................38 
8.1.4. 
Distribution of Reminder Cards ..................................................................................38 
8.1.5. 
Demography and Medical History ..............................................................................38 
8.1.5.1. 
Demographics and General Medical History .............................................................38 
8.1.5.2. 
Disease Characteristics and Treatment History ..........................................................39 
8.2. 
Efficacy Assessments .................................................................................................39 
8.2.1. 
Tumor Imaging ...........................................................................................................39 
8.2.2. 
ECOG Performance Status .........................................................................................39 
 
40 
8.2.4. 
Medical Resource Utilization and Health Economics ................................................40 
8.3. 
Safety Assessments .....................................................................................................40 
8.3.1. 
Adverse Events ...........................................................................................................40 
8.3.2. 
Physical Examinations ................................................................................................41 
8.3.3. 
Vital Signs ..................................................................................................................41 
8.3.4. 
Electrocardiograms .....................................................................................................42 
8.3.5. 
Comprehensive Eye Examination...............................................................................42 


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8.3.6. 
Laboratory Assessments .............................................................................................42 
8.3.6.1. 
Pregnancy Testing ......................................................................................................45 
8.3.6.2. 
Serology ......................................................................................................................45 
 
45 
 
45 
 
46 
 
46 
 
46 
 
46 
8.6. 
Unscheduled Visits .....................................................................................................47 
8.7. 
End of Treatment and/or Early Termination ..............................................................47 
8.8. 
Follow-Up ...................................................................................................................47 
8.8.1. 
Safety Follow-Up ........................................................................................................47 
8.8.2. 
Post-Treatment Disease Follow-Up ............................................................................47 
8.8.3. 
Survival Follow-Up ....................................................................................................48 
9. 
ADVERSE EVENTS: DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................49 
9.1. 
Definition of Adverse Event .......................................................................................49 
9.2. 
Definition of Serious Adverse Event ..........................................................................50 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse Events .........51 
9.4. 
Reporting of Serious Adverse Events .........................................................................53 
9.5. 
Events of Clinical Interest ..........................................................................................54 
9.6. 
Emergency Unblinding of Treatment Assignment .....................................................54 
9.7. 
Pregnancy ...................................................................................................................55 
9.8. 
Warnings and Precautions ..........................................................................................55 
9.9. 
Product Complaints ....................................................................................................55 
9.10. 
Treatment of Overdose ...............................................................................................56 
10. 
STATISTICS ..............................................................................................................57 
10.1. 
Sample Size Determination ........................................................................................57 
10.2. 
Populations for Analyses ............................................................................................57 
10.3. 
Level of Significance ..................................................................................................57 
10.4. 
Statistical Analyses .....................................................................................................57 
10.4.1. 
Primary Analysis ........................................................................................................57 


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10.4.2. 
Secondary Analysis ....................................................................................................58 
10.4.3. 
Safety Analyses ..........................................................................................................58 
10.5. 
Interim Analysis ..........................................................................................................59 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................60 
11.1. 
Investigator Responsibilities .......................................................................................60 
11.1.1. 
Identification of the Coordinating Principal Investigator ...........................................61 
11.2. 
Data Management .......................................................................................................61 
11.3. 
Data Privacy and Confidentiality of Study Records ...................................................63 
11.4. 
Financial Disclosure ...................................................................................................63 
11.5. 
Publication Policy .......................................................................................................64 
11.6. 
Study and Site Closure................................................................................................64 
12. 
REFERENCES ...........................................................................................................65 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS AND DEFINITIONS ............................................68 
APPENDIX B. FGF/FGFR TESTING AND ALTERATIONS .................................................70 
APPENDIX C. INSTRUCTION TO PARTICIPANTS FOR HANDLING STUDY 
DRUG .........................................................................................................................71 
APPENDIX D. MANAGEMENT OF POTENTIAL HY'S LAW CASES ................................72 
APPENDIX E. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS .......................................................................................................76 
APPENDIX F. CYP3A4 INHIBITORS AND INDUCERS .......................................................78 
APPENDIX G. PROTOCOL AMENDMENT SUMMARY OF CHANGES ...........................81 
 


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LIST OF TABLES 
Table 1: 
Primary and Major/Key Secondary Objectives and Endpoints ..................................11 
Table 2: 
Key Study Design Elements .......................................................................................12 
Table 3: 
Schedule of Activities .................................................................................................14 
Table 4: 
Objectives and Endpoints ...........................................................................................20 
Table 5: 
Exclusionary Laboratory Values ................................................................................26 
Table 6: 
Study Treatment Information .....................................................................................28 
Table 7: 
Guidelines for Interruption and Restarting of Study Drug .........................................30 
Table 8: 
Recommended Approach for Hyperphosphatemia Management ...............................32 
Table 9: 
ECOG Performance Status .........................................................................................40 
Table 10: Required Laboratory Analytes ....................................................................................44 
45 
47 
Table 13: Populations for Analysis .............................................................................................57 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................13 
Figure 2: 
FGFR Driver Mutations in NSCLC ............................................................................18 
 


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LIST OF ABBREVIATIONS 
Abbreviations and 
Special Terms 
Definition 
AE 
adverse event 
AJCC 
American Joint Committee on Caner 
ALP 
alkaline phosphatase 
ALT 
alanine transaminase 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
AST 
aspartate transaminase 
cfDNA 
cell-free deoxyribonucleic acid 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
 
 
CNS 
central nervous system 
CPS 
combined positive score 
CR 
complete response 
CRF 
case report form 
CSR 
Clinical Study Report 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DOR 
duration of response 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EGFR 
epidermal growth factor receptor 
 
 
EOT 
end of treatment  
 
 
FDA 
Food and Drug Administration 
FGF 
fibroblast growth factor 
FGFR 
fibroblast growth factor receptor 
FGFR1-3 
fibroblast growth factor receptor 1, 2, or 3 
FISH 
fluorescent in-situ hybridization 


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Abbreviations and 
Special Terms 
Definition 
FMI 
Foundation Medicine, Inc 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
human immunodeficiency virus 
HRT 
hormone replacement therapy 
IB 
Investigator's Brochure 
ICF 
informed consent form  
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
ICR 
independent central radiology 
IEC 
independent ethics committee 
ILD 
interstitial lung disease 
IMP 
investigational medicinal product 
INR 
international normalized ratio 
IO 
immuno-oncology 
IRB 
institutional review board 
IRT 
interactive response technology  
MedDRA 
Medical Dictionary for Regulatory Activities 
NSCLC 
non–small cell lung cancer 
OCT 
optical coherence tomography 
ORR 
objective response rate 
OS 
overall survival 
PD 
progressive disease 
PD-1 
programmed death 1 
PD-L1 
programmed death-ligand 1 
PFS 
progression-free survival 
PHL 
potential Hy's law 
PK 
pharmacokinetic 
PR 
partial response 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
QD 
once daily 


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Abbreviations and 
Special Terms 
Definition 
QTcF 
QT interval corrected using Fridericia's formula 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RSI 
reference safety information 
SAE 
serious adverse event 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 (a strain of the coronavirus 
family causing coronavirus disease 2019) 
SoA 
schedule of activities 
SOP 
standard operating procedure 
SRD/RPED 
serous retinal detachment/retinal pigmented epithelium detachment 
TEAE 
treatment-emergent adverse event 
TKI 
tyrosine kinase inhibitors 
TPS 
tumor proportion score 
ULN 
upper limit of normal 
WBC 
white blood cell 
WOCBP 
woman of childbearing potential 


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1. 
PROTOCOL SUMMARY 
Protocol Title: 
A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of 
Pemigatinib in Participants With Advanced Non–Small Cell Lung Cancer With an FGFR 
Alteration Who Progressed on Previous Therapy (FIGHT-210) 
Protocol Number: INCB 54828-210 
Objectives and Endpoints: 
Table 1 presents the primary and major/key secondary objectives and endpoints. 
Table 1: 
Primary and Major/Key Secondary Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To determine the efficacy of pemigatinib in 
participants in Cohort A 
ORR in Cohort A, defined as the proportion of 
participants who achieve a CR or PR based on 
RECIST v1.1. Response will be determined by an 
ICR review. 
Secondary 
To evaluate the efficacy of pemigatinib in 
participants in Cohort B 
ORR in Cohort B, defined as the proportion of 
participants who achieve a CR or PR based on 
RECIST v1.1. Response will be determined by an 
ICR review. 
To evaluate the efficacy of pemigatinib in 
Cohort A 
• PFS in Cohort A, defined as the time from the 
first dose of study drug until PD (according to 
RECIST v1.1 as assessed by an ICR review) or 
death, whichever is first. 
• DOR in Cohort A, defined as the time from the 
date of the first CR or PR until the date of the 
first PD (according to RECIST v1.1 as assessed 
by an ICR review) or death, whichever is first. 
• OS in Cohort A, defined as the time from the 
first dose of study drug to death of any cause. 
To assess safety and tolerability of pemigatinib in 
all participants 
Safety and tolerability, as assessed by the 
occurrence of TEAEs and treatment-related 
TEAEs according to NCI CTCAE v5.0, physical 
examination changes, vital sign changes, 
laboratory evaluations, and ECGs. 


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Overall Design: 
Table 2 presents the key study design elements. Further study details are presented after the 
table. 
Table 2: 
Key Study Design Elements 
Study Phase 
Phase 2 
Clinical Indication 
Treatment of patients with advanced NSCLC 
Population 
Male and female participants at least 18 years of age who have squamous or 
nonsquamous NSCLC with a documented FGFR1-3 mutations or 
fusions/rearrangement who have progressed on prior therapies and have no 
available standard treatment options 
Number of 
Participants 
Approximately 125 participants will be enrolled; Cohort A (squamous 
NSCLC) will enroll approximately 100 participants, and Cohort B 
(nonsquamous NSCLC) will enroll approximately 25 participants 
Study Design 
Single-arm, open-label, multi-center 
Estimated Duration of 
Study Participation 
Up to 30 days for screening, treatment in consecutive 21-day cycles 
utilizing the intermittent dosing schedule (2 weeks on treatment and 1 week 
off treatment) as long as the participant is receiving benefit and has not met 
any criteria for study withdrawal, and 30 to 35 days for safety follow-up. It 
is estimated that an individual will participate for approximately 9 months. 
Data Monitoring 
Committee 
No 
Coordinating Principal 
Investigator 
To be determined 
Treatment Groups and Duration: 
Due to the different histology (eg, squamous, nonsquamous, and large cell) and genetic markers 
(eg, EGFR mutant), participants enrolled in this study will be assigned to 1 of 2 cohorts as 
follows: 
• Cohort A: squamous NSCLC with known or likely FGFR1-3 driver mutations outside 
the kinase domain or fusions/rearrangements (n ≈ 100). 
• Cohort B: nonsquamous NSCLC with known or likely FGFR1-3 driver mutations 
outside the kinase domain or fusions/rearrangements, including participants who have 
relapsed on prior targeted therapy (n ≈ 25). 
See Figure 1 for an overview of the study design. 


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Figure 1: 
Study Design Schema 
 
Second-line plus FGFR1-3 mutations or fusion/rearrangement positive NSCLC
Cohort B:
Nonsquamous 
NSCLC
Cohort A:
Squamous NSCLC
Starting dose:
13.5 mg QD
Intermittent dosing 
schedule
Disease 
assessments 
every 3 cycles
SD, PR, CR:  Continue 
pemigatinib and regular 
disease assessments
PD:  Discontinue 
pemigatinib and move 
into follow up
Enroll


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Table 3: 
Schedule of Activities 
Visit Day (Range) 
Screening 
Treatment 
EOT 
Follow-Up 
Notes 
Days 
−30 to −1 
Cycle 1 
Other Cycles 
Safety 
(EOT + 
30-35 days) Disease Survival 
Day 1 
Day 8 
(± 3 days) 
Day 15 
(± 3 days) 
Day 1 
(± 3 days) 
Administrative procedures 
Informed consent 
X 
 
 
 
 
 
 
 
 
Section 8.1.1 
Documented FGFR status 
X 
 
 
 
 
 
 
 
 
Local or central (see Section 8.5.1) 
Contact IRT 
X 
X 
 
 
X 
X 
X 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
Demographics and general 
and disease medical history 
X 
 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Dispense study drug 
 
X 
X 
 
X 
 
 
 
 
 
Collect study drug/assess 
compliance 
 
 
X 
X 
X 
X 
 
 
 
 
Distribute reminder card 
 
X 
X 
X 
X 
 
 
 
 
 
Safety assessments 
AE assessments 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Physical examination 
(including height and weight) 
X* 
X† 
X† 
X† 
X† 
X† 
X† 
 
 
*Comprehensive including height. 
†Targeted associated with symptoms; does not 
include height. 
Vital signs  
X 
X 
 
 
X 
X 
X 
 
 
 
12-lead ECG 
X 
X 
 
 
X 
X 
X 
 
 
 
Comprehensive eye exam 
(slit-lamp, visual acuity, 
funduscopy with digital 
imaging, and OCT) 
X 
 
 
 
X* 
X 
 
 
 
*At least every 3 cycles or as clinically 
indicated starting at Cycle 3. 
Efficacy assessments 
Disease assessment (CT/MRI) 
X 
 
 
 
X* 
X 
 
X† 
 
Section 8.2.1 
*Every 3 cycles, starting at Cycle 3. To be 
completed as close to the end of the cycle as 
possible. 
†Every 12 weeks ± 7 days (see Section 8.8.2). 
ECOG performance status 
X 
X 
 
 
X 
 
 
 
 
 
Survival status 
 
 
 
 
 
 
 
 
X 
Via phone call, email, or visit at least every 
12 weeks (see Section 8.8.3). 


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Table 3: 
Schedule of Activities (Continued) 
Visit Day (Range) 
Screening 
Treatment 
EOT 
Follow-Up 
Notes 
Days 
−30 to −1 
Cycle 1 
Other Cycles 
Safety 
(EOT + 
30-35 days) Disease Survival 
Day 1 
Day 8 
(± 3 days) 
Day 15 
(± 3 days) 
Day 1 
(± 3 days) 
Laboratory assessments 
Blood chemistries 
X 
X* 
X 
X 
X 
X 
X 
 
 
*If drawn for screening no more than 3 days 
before Cycle 1 Day 1, sample not required. 
Hematology 
X 
X* 
X 
X 
X 
X 
X 
 
 
*If drawn for screening no more than 3 days 
before Cycle 1 Day 1, sample not required. 
Endocrine (PTH only) 
X 
X* 
 
 
X 
X 
 
 
 
*If drawn for screening no more than 3 days 
before Cycle 1 Day 1, sample not required. 
Coagulation 
X 
X* 
X 
X 
X 
X 
X 
 
 
*If drawn for screening no more than 3 days 
before Cycle 1 Day 1, sample not required. 
Pregnancy testing 
X* 
X 
 
 
X 
X 
X 
 
 
*Serum 
Serology 
X 
 
 
 
 
 
 
 
 
 
Urinalysis 
X 
 
 
 
X 
X 
 
 
 
 
Genetic testing 
Tumor tissue 
sampling/archival tissue 
X* 
 
 
 
 
X 
 
 
 
Section 8.5.1 
*Archival tissue; local/prior genomics reports 
acceptable. 
 


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2. 
INTRODUCTION 
2.1. 
Background 
Recent advances in oncology have improved understanding of the role of cancer biomarkers, 
which has led to the development of innovative drugs targeting the molecular profile of patients. 
Many targeted therapies are now included in treatment guidelines and have shifted clinical 
practice to utilize genomic information as an integral component of clinical decision-making 
(NCCN 2021). Molecular alterations in specific kinases can result in constitutive activity and 
drive initiation and progression of cancer. Biomarker-driven treatments with targeted therapies 
are now standard of care in certain cancers such as NSCLC (NCCN 2021). 
Pemigatinib is an inhibitor of the FGFR family of receptor tyrosine kinases that is proposed for 
the treatment of NSCLC. Aberrant signaling through FGFR resulting from gene amplification or 
mutation, chromosomal translocation, or 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 pemigatinib for the treatment of 
advanced NSCLC with documented select FGFR driver mutations and fusions/rearrangements. 
Refer to the IB for additional background information on pemigatinib. 
2.1.1. 
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 FGR ligands, divided into 
canonical and hormonal FGFs, 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, which leads to activation of the RAS-mitogen–activated protein kinase and phosphoinositide 
3-kinase–protein kinase B pathways and of the 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 FGFR1-3 have been described in 


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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. 
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 a genetically activated FGFR pathway sensitizes 
FGFR-altered cancer cells to knockdown or inhibition of these receptors (Kunii et al 2008, 
Lamont et al 2011, Nakamura et al 2015, Qing et al 2009, Sia et al 2015, Weiss et al 2010). 
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 several clinical studies of selective FGFR inhibitors, including pemigatinib, have 
shown a tolerable safety profile for the class and proven clinical benefit in patients with 
FGF/FGFR alterations. Pemazyre® (2021), Truseltiq™ (2021), and Balversa® (2020) are recently 
approved FGFR inhibitors. An on-target pharmacologic effect of FGFR inhibition in clinical 
studies is hyperphosphatemia and is managed with diet modifications and phosphate binders. 
Pemigatinib is a potent, selective, inhibitor of FGFR1-3 and is proposed for the treatment of 
participants with advanced NSCLC who have documented select FGFR driver mutations or 
fusions/rearrangements. 
2.1.2. 
Non–Small Cell Lung Cancer 
Lung cancer is the second most common primary cancer with a global incidence of 
approximately 53.1% (GLOBOCAN 2020). While the number of patients diagnosed with lung 
cancer has been slowly declining over the past few decades, it is still the leading cause of 
cancer-related deaths worldwide (Jemal et al 2011). Lung cancer is either NSCLC, which makes 
up approximately 80% of lung cancer, or small-cell lung cancer, which is around 20% of the 
lung cancer population (Rades et al 2012). 
Non–small cell lung cancer has 3 pathologic subtypes: squamous cell carcinoma, large cell 
carcinoma, and adenocarcinoma, also referred to as nonsquamous cell carcinoma. Nonsquamous 
cell carcinoma is the most prevalent subtype followed by squamous cell and large cell 
(Dela Cruz et al 2011). Within the nonsquamous cell subtype is a genetic profile based on the 
EGFR, which can be mutant-positive or wild-type. The EGFR status will determine the first-line 
treatment options. 
With the adoption of TKI, specifically EGFR inhibitors like gefitinib, erlotinib (first-generation 
TKI), and osimertinib (third-generation TKI) there has been a shift in the treatment landscape 
options for patients with EGFR-mutant NSCLC (Le and Gerber 2019). The TKIs provide a more 


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favorable response rate of around 50% to 60% coupled with a longer PFS when compared 
directly with platinum based chemotherapy (Chantharasamee et al 2019). Results of the 
OPTIMAL study showed PFS of erlotinib to be 13.1 months compared with chemotherapy, 
which was 4.1 months (Zhou et al 2011). 
First-line therapy for squamous NSCLC is typically a regimen that has a cisplatin backbone and 
includes agents like gemcitabine (Levy et al 2019). These platinum-based regimens are 
well-established with a response rate of around 17% to 22% and a 1-year survival rate of around 
30% (Fennell et al 2016). 
The discovery of PD-(L)1 markers in cancer ushered in a new wave of compounds to combat 
lung cancer. Checkpoint inhibitors like pembrolizumab (anti–PD-1; Keytruda® 2021) and 
atezolizumab (anti–PD-L1; Tecentriq® 2021) were added to the treatment arsenals and 
administered either as monotherapy or in combination with chemotherapy (NCCN 2021). 
Parameters for dosing with IO compounds is based on a score for PD-(L)1 levels. Using either 
the CPS or TPS, the physician determines the expression level of the PD-(L)1. The higher the 
score (eg, CPS of > 10 or TPS of > 50%), there is an increased chance of a robust response from 
treatment with the checkpoint inhibitor. 
Fibroblast growth factor receptor driver mutations and fusions/rearrangements add another 
treatment pathway option for patients with NSCLC. The frequency of FGFR1-3 mutations and 
rearrangements in squamous NSCLC is around 3% and 0.5% in nonsquamous NSCLC. This 
translates into approximately 1% to 2% for the entire NSCLC population (Helsten et al 2016). 
Some alterations are more prevalent than others with distributions highlighted in Figure 2 
(Campbell et al 2016). 
Figure 2: 
FGFR Driver Mutations in NSCLC 
 
2.2. 
Study Rationale 
Pemigatinib is a potent, selective inhibitor of FGFR1-3. This compound is proposed for the 
treatment of participants with advanced NSCLC harboring select FGFR driver mutations and 
fusions/rearrangements. 
2.2.1. 
Scientific Rationale for Study Design 
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, 


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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 in which 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). Pemigatinib is a potent inhibitor of the kinase activity of FGFR1-3 and has been 
shown to inhibit growth in several tumor models. This study has been designed as a single-arm, 
open-label study to evaluate the efficacy and safety of pemigatinib in participants with 
previously treated NSCLC harboring an activating FGFR1-3 mutation or fusion/rearrangement. 
An ICR group will evaluate tumor response to support the primary and secondary endpoints to 
minimize bias. 
2.2.2. 
Justification for Dose 
Pemigatinib has been studied using an intermittent dose regimen (2 weeks on treatment and 
1 week off treatment) as well as a continuous dose regimen (no treatment break). Data from 
several studies with pemigatinib utilizing both treatment regimens have shown a tolerable safety 
profile, confirmed efficacy in cholangiocarcinoma with FGFR2 rearrangements 
(Pemazyre 2021), and efficacy signals in other tumor types that have select FGFR driver 
mutations and fusions/rearrangements (refer to the IB for additional details). 
This study will utilize the intermittent dosing regimen, which was recommended based on safety, 
PK, preliminary signals of clinical benefit, and has been shown to have efficacy in 
cholangiocarcinoma. This regimen will allow for a more favorable safety profile with a 1-week 
dose holiday to allow toxicities to recover and avoid cumulative toxicities. 
2.3. 
Benefit/Risk Assessment 
Targeted therapies with a manageable safety profile that can provide a durable response and/or 
significant disease control in a molecularly defined population would provide a meaningful 
clinical benefit. To date, pemigatinib has been administered to over 900 patients across 
7 Incyte-sponsored clinical trials and commercially (Pemazyre 2021); it has an established 
clinical benefit in cholangiocarcinoma as well as a robust safety profile. In an earlier clinical trial 
(Study INCB 54828-101), pemigatinib was tested in several participants with NSCLC and 
showed a favorable risk/benefit ratio for further development of pemigatinib in this population. 
The most frequently reported TEAEs associated with pemigatinib use includes 
hyperphosphatemia, nail toxicity, and hypophosphatemia. Rare but significant AEs associated 
with pemigatinib use include serous retinal detachment and soft tissue mineralization including 
calcinosis and calciphylaxis. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of pemigatinib may be found in the IB. 


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3. 
OBJECTIVES AND ENDPOINTS 
Table 4 presents the objectives and endpoints. 
Table 4: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To determine the efficacy of pemigatinib in 
participants in Cohort A 
ORR in Cohort A, defined as the proportion of 
participants who achieve a CR or PR based on 
RECIST v1.1. Response will be determined by an 
ICR review. 
Secondary 
To evaluate the efficacy of pemigatinib in 
participants in Cohort B 
ORR in Cohort B, defined as the proportion of 
participants who achieve a CR or PR based on 
RECIST v1.1. Response will be determined by an 
ICR review. 
To evaluate the efficacy of pemigatinib in 
Cohort A  
• PFS in Cohort A, defined as the time from the 
first dose of study drug until PD (according to 
RECIST v1.1 as assessed by an ICR review) or 
death, whichever is first. 
• DOR in Cohort A, defined as the time from the 
date of the first CR or PR until the date of the 
first PD (according to RECIST v1.1 as assessed 
by an ICR review) or death, whichever is first. 
• OS in Cohort A, defined as the time from the 
first dose of study drug to death of any cause. 
To assess safety and tolerability of pemigatinib in 
all participants 
Safety and tolerability, as assessed by the 
occurrence of TEAEs and treatment-related 
TEAEs according to NCI CTCAE v5.0, physical 
examination changes, vital sign changes, 
laboratory evaluations, and ECGs. 


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Table 4: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 
Exploratory 
To evaluate the efficacy of pemigatinib in 
Cohort B 
• PFS in Cohort B, defined as the time from the 
first dose of study drug until PD (according to 
RECIST v1.1 as assessed by an ICR review) or 
death, whichever is first. 
• DOR in Cohort B, defined as the time from the 
date of the first CR or PR until the date of the 
first PD (according to RECIST v1.1 as assessed 
by an ICR review) or death, whichever is first. 
• OS in Cohort B, defined as the time from the 
first dose of study drug to death of any cause. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is an open-label, monotherapy study of pemigatinib in participants with advanced NSCLC 
with an FGFR alteration. The study comprises 2 cohorts, Cohort A and Cohort B, and will enroll 
approximately 125 participants. Participants will receive pemigatinib 13.5 mg QD on an 
intermittent dose schedule. Full study drug administration information can be found in Section 6. 
All potential participants must have documented FGFR1-3 mutations or fusions/rearrangements 
before enrollment. Acceptable FGFR alterations may be classified as fusion, rearrangement, 
translocation, mutation, or FISH-positive. See Appendix B for the list of known/likely actionable 
FGFR1-3 alterations. Participants may be enrolled and start receiving treatment based on a local 
genomics report (non-FMI and commercial FMI reports) or the sponsor-designated central 
genomics laboratory report. Participants enrolled based on a local genomics report must be 
confirmed through the sponsor's central genomics laboratory for confirmation of FGFR alteration 
(results from central review are not required before the first dose). Participants enrolled based on 
commercial FMI reports are not required to send samples for confirmation through the sponsor's 
central genomics laboratory. 
Previous therapies may include targeted therapies, chemotherapeutic agents, and 
immunotherapies, with or without radiotherapy. Participants receiving radiotherapy to target 
lesion(s) must show progression of the target lesion before entry into the study. 
Due to the different histology (eg, squamous, nonsquamous, and large cell) and genetic markers 
(eg, EGFR mutant), participants enrolled in this study will be assigned to 1 of 2 cohorts as 
follows: 
• Cohort A: squamous NSCLC with known or likely FGFR1-3 driver mutations outside 
the kinase domain or fusions/rearrangements (n ≈ 100). 
• Cohort B: nonsquamous NSCLC with known or likely FGFR1-3 driver mutations 
outside the kinase domain or fusions/rearrangements, including participants who have 
relapsed on prior targeted therapy (n ≈ 25). 
Treatment will start on Cycle 1 Day 1. Participants will undergo regular safety assessments 
during treatment as well as regular efficacy assessments. Participants will be allowed to continue 
study drug administration in 21-day cycles until documented disease progression or unacceptable 
toxicity is reported. See Figure 1 for the study design. 
4.2. 
Overall Study Duration 
The study begins when the first participant signs the study ICF. The end of the study is defined 
as the date of the last visit of the last participant in the study. 
The duration of the study will be up to 30 days for screening, treatment in consecutive 21-day 
cycles utilizing the intermittent dosing schedule (2 weeks on treatment and 1 week off 
treatment), as long as the participant is receiving benefit and has not met any criteria for study 
withdrawal, and 30 to 35 days for follow-up after the last dose of study drug. It is estimated that 
an individual will participate for approximately 9 months. 


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The end of the study may be designated as the timepoint when all participants have discontinued 
the study. If by the end of the study there remains at least 1 participant still on study treatment 
for at least 6 months, the participant(s) may enter additional treatment cycles. At this point, a 
database lock of the study may occur to allow the analysis of the study data, and the study may 
be considered completed. Any remaining participants may continue to receive study medication 
and be seen by the investigator per usual standard of care for this participant population. In 
addition, the investigator will be expected to monitor for and report any SAEs, ECIs, and 
pregnancies, as detailed in Section 9. The participant is considered on study until such time that 
they meet any of the discontinuation criteria and written notification is given to the sponsor or 
until the participant is moved to the rollover study, INCB 54828-801. 
4.3. 
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 IRB/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, for example, required by regulatory decision. 
If the study is terminated prematurely, the sponsor will notify the investigators, the IRBs and 
IECs, and the regulatory bodies of the decision and reason for termination of the study. 


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5. 
STUDY POPULATION 
Deviations from eligibility criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability, and/or participant safety. Therefore, 
adherence to the criteria as specified in the Protocol is essential. Prospective approval of Protocol 
deviations to recruitment and enrollment criteria, also known as Protocol waivers or exemptions, 
are not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1. Age 18 years or older, inclusive at the time of signing the ICF. 
2. Histologically or cytologically confirmed advanced or metastatic NSCLC (Stage IIIB/C 
or IV per the AJCC Cancer Staging Manual, 8th Edition [Rami-Porta et al 2017]). Both 
squamous and nonsquamous NSCLC are eligible. 
3. Radiographically measurable disease (per RECIST v1.1). Tumor lesions located in a 
previously irradiated area, or in an area subjected to other loco-regional therapy, are 
considered measurable if progression has been clearly demonstrated in the lesion. 
4. Documentation of known/likely actionable known or likely FGFR1-3 alterations (see 
Appendix B). 
5. Must have objective documented progression after at least 1 prior therapy, and must have 
no therapy available that is likely to provide clinical benefit. Participants who are 
intolerant of or decline the approved therapy are eligible only if they have no therapy 
available that is likely to provide clinical benefit. 
6. ECOG performance status of 0 to 2. 
7. Baseline archival tumor specimen (if less than 24 months from date of screening) or 
willingness to undergo a pretreatment tumor biopsy to obtain the specimen. Must be a 
tumor block or approximately 15 unstained slides from biopsy or resection of primary 
tumor or metastasis. 
8. Willingness to avoid pregnancy or fathering children based on the criteria below. 
a. Male participants with reproductive potential must agree to take appropriate 
precautions to avoid fathering children from screening through 90 days (a 
spermatogenesis cycle) after the last dose of study drug and must refrain from 
donating sperm during this period. Permitted methods in preventing pregnancy (see 
Appendix A) should be communicated to the participants and their understanding 
confirmed. 
b. Female participants who are WOCBP must have a negative serum pregnancy test at 
screening and a negative urine pregnancy test before the first dose on Day 1 and must 
agree to take appropriate precautions to avoid pregnancy from screening through 
30 days (1 menstrual cycle) after the last dose of study drug and must refrain from 
donating oocytes during this period. Permitted methods in preventing pregnancy (see 
Appendix A) should be communicated to the participants and their understanding 
confirmed. 
c. A female participant not considered to be of childbearing potential as defined in 
Appendix A is eligible. 


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5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Prior receipt of a selective FGFR inhibitor. 
2. Receipt of anticancer medications or investigational drugs for any indication or reason 
within 28 days before the first dose of pemigatinib. Participants must have recovered 
(≤ Grade 1 as per CTCAE v5.0 or at pretreatment baseline) from AEs from previously 
administered therapies (excluding alopecia). 
3. Concurrent anticancer therapy (eg, chemotherapy, immunotherapy, biologic therapy, 
hormonal therapy, or investigational therapy). 
4. Candidate for potentially curative surgery. 
5. Current evidence of clinically significant corneal (including but not limited to 
bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and 
keratoconjunctivitis) or retinal disorder (including but not limited to macular/retinal 
degeneration, diabetic retinopathy, and retinal detachment) as confirmed by 
ophthalmologic examination. 
6. Radiation therapy administered for the treatment of cancer lesions within 2 weeks before 
enrollment/first dose of study drug. Participants must have recovered from all 
radiation-related toxicities, not require corticosteroids, and not have had radiation 
pneumonitis. Evidence of fibrosis within a radiation field from prior radiotherapy is 
permitted with medical monitor approval. A 1-week washout is permitted for palliative 
radiation to non-CNS disease. 
7. Untreated brain or CNS metastases or brain or CNS metastases that have progressed 
(eg, evidence of new or enlarging brain metastasis or new neurological symptoms 
attributable to brain or CNS metastases). Participants who have previously treated and 
clinically stable brain or CNS metastases are eligible if there is no evidence of 
progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical 
examination and brain imaging (MRI or CT scan) during the screening period, and if they 
are on a stable or decreasing dose of corticosteroids for at least 1 week. 
8. Known additional malignancy that is progressing or requires active treatment. Exceptions 
include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ 
cervical cancer that has undergone potentially curative therapy. 
9. Participants with laboratory values at screening defined in Table 5. 


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Table 5: 
Exclusionary Laboratory Values 
Laboratory Parameter 
Exclusion Criterion 
Hematology 
a 
Platelets 
≤ 75 × 109/L (transfusion allowed with a 2-week washout period) 
b 
Hemoglobin 
≤ 9.0 g/dL (transfusion allowed with a 2-week washout period) 
c 
ANC 
≤ 1.5 × 109/L 
Hepatic 
d 
ALT 
≥ 3 × ULN (> 5 × ULN for liver metastasis) 
e 
AST 
≥ 3 × ULN (> 5 × ULN for liver metastasis) 
f 
Total bilirubin 
≥ 1.5 × ULN (≥ 2.5 × ULN if Gilbert's syndrome or liver metastasis) 
g 
Alkaline phosphatase 
≥ 3 × ULN 
Renal 
h 
Serum creatinine clearance 
≤ 30 mL/minute based on Cockcroft-Gault formula 
Chemistry 
i 
Serum phosphate 
> ULN 
j 
Serum calcium 
Outside of normal range or serum albumin-corrected calcium 
outside of the normal range when serum albumin is outside of the 
normal range 
10. History of calcium and phosphate hemostasis disorder or systemic mineral imbalance 
with ectopic calcification of soft tissues (exception: commonly observed calcifications in 
soft tissues such as the skin, kidney tendon, or vessels due to injury, disease, or aging in 
the absence of systemic mineral imbalance). 
11. Gastrointestinal conditions/disorders that may raise gastric and/or small intestinal pH that 
could interfere with absorption, metabolism, or excretion of pemigatinib. 
12. Inability to swallow and retain oral medication. 
13. Clinically significant or uncontrolled cardiac disease, including unstable angina, acute 
myocardial infarction within 6 months before Day 1 of study drug administration, New 
York Heart Association Class III or IV congestive heart failure, and uncontrolled 
arrhythmia (participants with pacemaker or with atrial fibrillation and well-controlled 
heart rate are allowed). 
14. History or presence of an abnormal ECG that, in the investigator's opinion, is clinically 
meaningful. A screening QTcF interval > 480 milliseconds is excluded. For participants 
with an intraventricular conduction delay (QRS interval > 120 ms), the JTc interval may 
be used in place of the QTcF with medical monitor approval. The JTc must be 
≤ 340 milliseconds if JTc is used in place of the QTcF. 
15. Active chronic or current infectious disease requiring systemic antibiotic, antifungal, or 
antiviral treatment within 2 weeks before enrollment (participants with asymptomatic 
chronic infections on prophylactic treatment are allowed). 


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16. Evidence of active HBV or HCV infection (defined as participants with elevated 
transaminases or cirrhosis. Participants with chronic HBV/HCV infection with no 
cirrhosis and no elevated transaminases are allowed. 
17. Known HIV infection with a CD4+ T-cell count < 350 cells/µL will be excluded. 
Participants with CD4+ T-cell (CD4+) counts ≥ 350 cells/μL should generally be eligible. 
18. Current use of prohibited medication as described in Section 6.6.2. 
19. Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers (see 
Appendix F) within 14 days or five half-lives (whichever is longer) before the first dose 
of study drug/treatment. Moderate CYP3A4 inhibitors are not prohibited, but should be 
avoided (Section 6.6.1). 
20. Known hypersensitivity or severe reaction to pemigatinib or excipients of pemigatinib 
(refer to the IB). 
21. Inability or unlikeliness of the participant to comply with the dose schedule and study 
evaluations, in the opinion of the investigator. 
22. Inadequate recovery from toxicity and/or complications from a major surgery before 
starting therapy. 
23. Women who are pregnant or breastfeeding. 
24. Any condition that would, in the investigator's judgment, interfere with full participation 
in the study, including administration of study drug/treatment and attending required 
study visits; pose a significant risk to the participant; or interfere with interpretation of 
study data. 
25. Inability of the participant (or legally authorized representative) to comprehend the ICF 
or unwillingness to sign the ICF. 
26. History of hypovitaminosis D requiring supraphysiologic doses (eg, 50,000 UI/weekly) to 
replenish the deficiency. Vitamin D supplements are allowed. 
27. The following are excluded in France: vulnerable populations according to article 
L.1121-6 of the French Public Health Code and adults under legal protection or who are 
unable to express their consent per article L.1121-8 of the French Public Health Code. 
28. Any evidence of current ILD or pneumonitis or a prior history of ILD or non-infectious 
pneumonitis requiring high-dose glucocorticosteroids. 
5.3. 
Lifestyle Considerations 
Participants should refrain from consumption of red wine, Seville oranges, grapefruit or 
grapefruit juice from 7 days before the start of study drug administration until after the final dose 
of study drug. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently enrolled in the study. 


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Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened 1 time. 
Tests with results that fail eligibility requirements may be repeated once during screening if the 
investigator believes the result to be in error. Additionally, a participant who fails screening may 
repeat the screening process 1 time if the investigator believes that there has been a change in 
eligibility status. Participants who rescreen must reconsent and be assigned a new participant 
number. 
5.5. 
Replacement of Participants 
No participants will be replaced at any time during this study. 
6. 
STUDY TREATMENT 
Pemigatinib will be self-administered as a QD oral treatment on a 21-day cycle. Participants will 
take study drug every day for 2 weeks followed by no study drug for 1 week (dose holiday). The 
starting dose will be 13.5 mg. Each dose of study drug should be taken in the morning, with or 
without food. 
6.1. 
Study Treatment Administered 
Table 6 presents the study treatment information. 
Table 6: 
Study Treatment Information 
Study Treatment Name 
Pemigatinib 
Mechanism of Action 
Pan-FGFR inhibitor 
Dosage Formulation 
Tablet 
Unit Dose Strengths 
4.5, 9, and 13.5 mg 
Administration Instructions 
Take pemigatinib first thing in the morning with a full glass of water, 
with or without food. Pemigatinib should be taken every day for 
2 weeks followed by no pemigatinib for 1 week (dose holiday). 
Packaging and Labeling 
Pemigatinib will be provided in plastic bottles. Each bottle will be 
labeled as required per country requirement. 
Storage 
Room temperature (15°C-30°C) 
Status of Treatment in 
Participating Countries 
Investigational 
6.2. 
Preparation, Handling, and Accountability 
The investigator or designee, must confirm appropriate temperature conditions have been 
maintained during transit for all study treatments received and any discrepancies are reported and 
resolved before use of the study treatment. 
Only participants enrolled in the study may receive study treatment, and only authorized site 
staff may supply or administer study treatment. All study treatment must be stored in a secure, 


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environmentally controlled, and monitored (manual or automated) area in accordance with the 
labeled storage conditions with access limited to the investigator and authorized site staff. 
The investigator, (or designee) is responsible for study treatment accountability, reconciliation, 
and record maintenance (ie, receipt, reconciliation, and final disposition records). 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 the following: 
• Delivery of study drug to the study site. 
• Inventory of study drug at the site. 
• Participant use of the study drug, including tablet counts from each supply dispensed. 
• Return of study drug to the investigator or designee by participants. 
The investigational product must be used only in accordance with the Protocol (see Appendix C). 
The investigator will also maintain records adequately documenting that the participants 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 participants. 
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 SOPs. If local procedures 
mandate on-site destruction of the 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. 
Further guidance and information for the final disposition of unused study treatments are 
provided in the Pharmacy Manual. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
This is an open-label, nonrandomized study; no comparisons will be made between participants 
or against historical controls. Measurements of safety and efficacy are objective measurements, 
and only comparisons to pretreatment conditions will be made. 
6.4. 
Study Treatment Compliance 
Compliance with all study-related treatments should be emphasized to the participant by the site 
personnel, and appropriate steps should be taken to optimize compliance during the study. 
Compliance with study drug will be calculated by the sponsor based on the drug accountability 
(eg, tablet counts) documented by the site staff and monitored by the sponsor/designee. 
Participants will be instructed to bring all unused study drugs with them to the study visits in 
order for site personnel to conduct tablet counts to assess study drug accountability. 


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6.5. 
Dose Modifications 
Individual decision regarding dose modifications of pemigatinib should be made using clinical 
judgment and in consultation with the sponsor's medical monitor, taking into account relatedness 
of the AE to the study treatment and the participant's underlying condition. 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. 
6.5.1. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study Drug 
Safety concerns should be discussed with the sponsor immediately upon occurrence or awareness 
to determine if the participant should continue or discontinue study treatment. 
Treatment with pemigatinib may be delayed up to 2 weeks (14 days) to allow for resolution of 
toxicity. Participants may resume treatment if no medical condition or other circumstance exists 
that, in the opinion of the investigator, would make the participant unsuitable for further 
participation in the study. The treating investigator should contact the sponsor to discuss the case 
of any participant whose treatment has been delayed for more than 14 days before restarting 
treatment with pemigatinib. See Table 7 for guidelines. 
Table 7: 
Guidelines for Interruption and Restarting of Study Drug 
Adverse Event 
Action Taken 
Chemistry 
• AST and/or ALT is > 5.0 × ULN. 
Note: In participants with liver 
metastasis–related elevations at 
baseline, contact sponsor to discuss 
clinical management and possible dose 
reductions. 
Step 1: Interrupt pemigatinib up to 2 weeks (14 days) until 
the toxicity has resolved to ≤ Grade 1 except by approval of 
the medical monitor. 
Step 2: Restart pemigatinib at same dose. If assessed as 
related to pemigatinib, restart pemigatinib at the next lower 
dose; monitor as clinically indicated. If AE persists for more 
than 1 cycle, consider a dose reduction. 
Other toxicities 
• Retinal pigment epithelium 
detachment 
Step 1: If RPE detachment is noted on an OCT examination, 
remain on study drug and follow up with OCT 
re-examination in 2 weeks. 
Step 2: If RPE detachment is noted on re-examination, 
reduce dose of pemigatinib and re-examine via OCT in 
2 weeks. 
Step 3: If RPE detachment is not resolving on re-
examination after dose reduction, further reduction of 
pemigatinib or dose hold until resolution of RPE detachment 
• Any Grade 1 or Grade 2 toxicity. 
Continue pemigatinib treatment and treat the toxicity; 
monitor as clinically indicated. 


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Table 7: 
Guidelines for Interruption and Restarting of Study Drug (Continued) 
Adverse Event 
Action Taken 
• Recurrent Grade 2 toxicity 
Step 1: Interrupt pemigatinib up to 2 weeks (14 days), until 
toxicity resolves to ≤ Grade 1 
Step 2: If related to pemigatinib, restart pemigatinib at the 
next lower dose level.  Monitor as clinically indicated and if 
AE persists, consider further dose reduction. 
• Any Grade 3 toxicity 
Step 1: Interrupt pemigatinib up to 2 weeks (14 days), until 
toxicity resolves to ≤ Grade 1. 
Step 2: Restart pemigatinib at same dose. If assessed as 
related to pemigatinib, restart pemigatinib at the next lower 
dose; monitor as clinically indicated. If AE persists for more 
than 1 cycle, consider a dose reduction. 
• Any recurrent Grade 3 toxicity after 
2 dose reductions. 
Discontinue pemigatinib administration and follow-up per 
Protocol. (Exceptions require approval of sponsor.) 
• Any other Grade 4 toxicity. 
• QT/QTc to > 500 ms or to > 60 ms 
over baseline. 
Discontinue pemigatinib administration and follow-up per 
Protocol. 
For participants who present with possible or confirmed SRD/RPED based on OCT, the 
guidelines in Table 7 should be followed. It is recommended to discuss the findings with the 
sponsor's medical monitor before making changes to the participant's treatment. 
Per CTCAE v 5.0, retinal detachment is graded as 3 (macular sparing) and 4 (macula‐off), but 
this refers to rhegmatogenous retinal detachment (when a hole occurs in the retina). There is no 
grading for SRD/RPED (no hole in the macula, just fluid accumulation). Therefore, grading 
should be based on the CTCAE v5.0 term of retinopathy. 
The starting dose of pemigatinib will be 13.5 mg QD, intermittent dosing regimen (2 weeks on 
treatment and 1 week off treatment). Dose reductions should follow as noted below: 
• Starting dose: 13.5 mg QD intermittent dosing 
• First dose reduction: 9 mg QD intermittent dosing 
• Second dose reduction: 4.5 mg QD intermittent dosing 
Dose reductions below 4.5mg QD are not allowed. Following a dose reduction and resolution of 
pemigatinib-related toxicities, a participant's dose may be returned to the starting dose at the 
discretion of the investigator and in consultation with the sponsor's medical monitor. 


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6.5.2. 
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 8. 
The use of diet modifications alone include food exchanges from high-phosphate foods to 
low-phosphate foods and can be implemented once serum phosphate levels are above the ULN 
but do not exceed 7.0 mg/dL. Diet modification should continue with the inclusion of phosphate 
binders once serum phosphate levels exceed 7.0 mg/dL. Examples of phosphate binders are 
sevelamer HCl (examples of name brands: Renegel® and Renvela®) or lanthanum HCl. 
Administration of phosphate binders should be 3 times per day (eg, with each meal) to reduce 
absorption of phosphate. Doses and frequency of doses should be based on the participant's 
tolerance for the binder and the control of the serum phosphate. If binders are used to manage 
hyperphosphatemia during treatment, it is recommended to stop binders, together with the 
low-phosphate diet, at the same time pemigatinib is stopped to reduce the risk of 
hypophosphatemia. 
Note that CTCAE v5.0 now has a category for grading hyperphosphatemia. 
Table 8: 
Recommended Approach for Hyperphosphatemia Management 
Serum 
Phosphate Level 
Supportive Care 
Guidance for 
Interruption/Discontinuation 
of Pemigatinib 
Guidance for Restarting 
Pemigatinib 
> 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. 
Monitor serum phosphate 
approximately twice a week, 
and adjust the dose of binders 
as needed; continue to 
monitor serum phosphate at 
least twice a week until level 
returns 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 
pemigatinib for up to 2 weeks.  
Restart at the same dose 
when serum phosphate is 
< 7 mg/dL. If serum 
phosphate level recurs at 
> 7 mg/dL, restart 
pemigatinib 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 
approximately twice a week 
until level returns to 
≤ 7 mg/dL. 
If serum phosphate level is 
> 10 mg/dL for 1 week 
following phosphate-binding 
therapy and low-phosphate 
diet, interrupt pemigatinib. If 
there is recurrence of serum 
phosphate level in this range 
following 2 dose reductions, 
permanently discontinue 
pemigatinib. 
Restart pemigatinib at 
reduced dose with 
phosphate binders when 
serum phosphate is 
< 7 mg/dL. 


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6.5.3. 
Criteria for Permanent Discontinuation of Study Drug 
The occurrence of unacceptable toxicity not caused by the underlying disease will require that 
the study drug be permanently discontinued. Unacceptable toxicity is defined as follows: 
• The occurrence of an AE that is related to study drug that, in the judgment of the 
investigator or the sponsor's medical monitor, compromises the participant's ability to 
continue study-specific procedures or is considered to not be in the participant's best 
interest. 
• An AE requiring more than 3 dose reductions. 
• A persistent AE requiring a delay of therapy for more than 2 weeks (14 days) unless a 
greater delay has been approved by the sponsor. 
See Section 7 for discontinuation procedures. 
6.6. 
Concomitant Medications and Procedures 
All concomitant medications and treatments (including over-the-counter or prescription 
medicines, vitamins, vaccines, and/or herbal supplements) must be recorded in the eCRF. Any 
prior medication received up to 30 days before the first dose of study drug through 30 to 35 days 
after the last dose of study drug, or until the participant begins a new anticancer therapy, 
whichever occurs first, will be recorded in the eCRF. Any addition, deletion, or change in the 
dose of these medications will also be recorded. Concomitant medications administered for 
treatment of SAEs (as defined in Section 9.2) should be recorded even if the SAE is reported 
beyond 30 to 35 days after the last dose of study drug. Concomitant treatments/procedures that 
are required to manage a participant's medical condition during the study will also be recorded in 
the eCRF. The medical monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
6.6.1. 
Restricted Medications and Procedures 
The use of mild CYP3A4 inhibitors or inducers, moderate CYP3A4 inhibitors, proton pump 
inhibitors, and OCT2 substrates should involve careful monitoring. If the use of moderate 
CYP3A4 inhibitors is unavoidable, the pemigatinib dose should be reduced by one level (unless 
at 4.5mg). Once concomitant use of moderate CYP3A4 inhibitor is discontinued, as well as 
3 half-lives of the CYP inhibitor, the dose of pemigatinib may be returned to the original dose. 
Calcium-based, phosphate-binding medications should not be used due to a concern for soft 
tissue mineralization. 
Palliative radiotherapy is permitted if considered of benefit and medically necessary by the 
investigator. The sponsor must be notified prior to start of any procedure that may be considered 
restricted. 


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6.6.2. 
Prohibited Medications and Procedures 
The following medications and measures are prohibited: 
• The concomitant administration of potent CYP3A4 inhibitors and inducers and 
moderate CYP3A4 inducers (see Appendix F). Based on the low overall 
bioavailability of topical ketoconazole, there are no restrictions on topical 
ketoconazole. 
• Any concomitant use of a selective FGFR inhibitor (other than the study drug). 
• Any other investigational study drug for any indication. 
• Use of any anticancer medications, treatments, or procedures other than the study 
drug. Discuss with the sponsor any treatment plans. 
The sponsor must be notified prior to start of any procedure that may be considered prohibited. 
6.7. 
Treatment After the End of the Study 
Upon completion of this study, for participants who are continuing to receive study drug and 
benefiting from treatment with pemigatinib, the rollover study, INCB 54828-801, is available. 


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7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
7.1.1. 
Reasons for Discontinuation 
Participants must be discontinued from study treatment for the following reasons: 
• The participant is confirmed to be pregnant. 
• Consent is withdrawn. 
Note: Study staff must differentiate if the participant is withdrawing consent for the 
entire study or just continuing treatment. Withdrawing consent for the study will 
mean that the participant has explicitly indicated that they do not want to be followed 
any longer; in this case no further data, except data in public domain, may be solicited 
from or collected on the participant. If a participant chooses to withdraw consent for 
continuing treatment, this participant will remain on the study and will be followed 
for progression and survival. 
• Further treatment would be injurious to the participant's health or well-being, in the 
investigator's medical judgment. The participant 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, as noted in Section 6.5. 
• Disease progression has been reported by the ICR. 
• Other antineoplastic treatment (not including palliative radiation) is initiated. 
A participant may be discontinued from study treatment as follows: 
• If, during the course of the study, a participant 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 participant should be 
discontinued from treatment. This includes cases where the local genomic testing 
result is positive for an acceptable FGFR alteration (see Appendix B) but the central 
genomic testing is not. 
• If a participant is noncompliant with study procedures or study drug administration in 
the investigator's opinion, the sponsor should be consulted for instruction on handling 
the participant. 
7.1.2. 
Discontinuation Procedures 
In the event that the decision is made to permanently discontinue the study treatment, the EOT 
visit should be conducted. Reasonable efforts should be made to have the participant return for a 
follow-up visit. These visits are described in Table 3. The last date of the last dose of study drug 
and the reason for discontinuation of study drug will be recorded in the eCRF. 


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If a participant is discontinued from study treatment: 
• The study monitor or sponsor must be notified. 
• The reason(s) for discontinuation must be documented in the participant's medical 
record and the primary reason for discontinuation must be included in the eCRF. 
• The EOT visit should be performed and date recorded. 
• The status of the participant should be updated to EOT in the IRT. 
• Participants must be followed for safety until the time of the follow-up visit or until 
study drug–related toxicities resolve, return to baseline, or are deemed irreversible, 
whichever is longest. 
If the participant 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, participants will have the option of withdrawing consent for study 
treatment but continuing in the follow-up period of the study for safety/efficacy assessments. 
7.2. 
Participant Withdrawal From the Study 
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons. 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the investigator must document this in the site study records. If the participant 
withdraws consent for disclosure of future information, the sponsor may retain and continue to 
use any data collected before such a withdrawal of consent. 
See Table 3 for data to be collected at the time of study withdrawal and follow-up and for any 
further evaluations that need to be completed. 
7.3. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant's last known mailing address 
or local equivalent methods). These contact attempts should be documented in the 
participant's medical record. 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 


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8. 
STUDY ASSESSMENTS AND PROCEDURES 
8.1. 
Administrative and General Procedures 
8.1.1. 
Informed Consent Process 
• The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions 
regarding the study. 
− Informed consent must be obtained before any study-related procedures are 
conducted, unless otherwise specified by the Protocol. 
− Informed consent must be obtained using the IRB/IEC-approved version in a 
language that is native and understandable to the participant. 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 participant records. 
− The ICF must contain all required elements and describe the nature, scope, and 
possible consequences of the study in a form understandable to the study 
participant. 
• Participants must be informed that their participation is voluntary. Participants or 
their legally authorized representative will be required to sign a statement of informed 
consent that meets the applicable requirements and regulations for the countries in 
which the study is being conducted as well as the IRB/IEC or study center. 
• The participant must be informed that his/her personal study-related data will be used 
by the sponsor in accordance with local data protection laws. The level of disclosure 
must also be explained to the participant. 
• The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
• Participants must provide consent to the most current version of the ICF during their 
participation in the study. 
• A copy of the ICF(s) must be provided to the participant or the participant's legally 
authorized representative. 
Participants who are rescreened are required to sign a new ICF and will be assigned a new 
participant number. 


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8.1.2. 
Screening Procedures 
Screening is the interval between signing the ICF and the day the participant is enrolled in the 
study (Cycle 1 Day 1). Screening may not exceed 30 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 participant's routine clinical management (eg, blood count, 
imaging study) and obtained before signing of the ICF may be used for screening or baseline 
purposes provided the procedure meets the Protocol-defined criteria and has been performed in 
the timeframe of the study as noted in this Protocol. For participants who are enrolled in the 
study, information associated with eligibility requirements must be entered into the appropriate 
eCRF pages. 
Results from the screening visit evaluations will be reviewed to confirm 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 eligibility. Treatment should start as soon as possible but 
within 3 days after the date of enrollment. 
See Sections 5.4 and 5.5 for information regarding screen failures and replacement of 
participants, respectively. 
8.1.3. 
Interactive Response Technology Procedure 
Each participant will be identified in the study by a participant ID number, which is a 
combination of a country's abbreviation, the site ID, and the participant number. Site staff should 
contact the IRT to obtain the participant ID number during screening. Upon determining that the 
participant is eligible for study entry, the IRT will be contacted to enroll the participant. 
Additionally, the IRT will be contacted on Day 1 of each cycle to update the study drug supply. 
Additional details are provided in the IRT Manual. 
8.1.4. 
Distribution of Reminder Cards 
Participants will be provided with a reminder card at each visit. The reminder card will indicate 
the date/time of the next visit. 
8.1.5. 
Demography and Medical History 
8.1.5.1. 
Demographics and General Medical History 
Demographic data and general medical history will be collected at screening by the investigator 
or qualified designee and will include year of birth/age, race, ethnicity, medical and surgical 
history, and current illnesses. Medical history will include relevant medical or surgical treatment 
within the last 10 years that are considered to be clinically significant by the investigator. 


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8.1.5.2. 
Disease Characteristics and Treatment History 
A disease-targeted medical and treatment history will be collected at screening. Details regarding 
the participant's malignancy under study, including date of diagnosis, initial and current cancer 
stage, tumor histology, relevant disease characteristics, and prior treatments, including systemic 
treatments, radiation, and surgical procedures will be recorded. 
8.2. 
Efficacy Assessments 
8.2.1. 
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 and head may be included if clinically indicated. In cases where participants are 
diagnosed with brain metastases prior to initiation of study, standard-of-care brain scans would 
be clinically appropriate. 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 9 weeks (ie, every 3 cycles starting at Cycle 3), and then at EOT (if applicable). If a 
participant discontinues before the first on-treatment assessment, and the baseline imaging was 
performed in the 2 weeks before Cycle 1 Day 1, then an EOT assessment is not required. 
Imaging should continue in 9-week intervals regardless of delays in cycle starts. For participants 
showing a response, a confirmatory scan may be performed a minimum of 4 weeks (per 
RECIST v1.1) from the previous scan. For participants showing a progression based on local 
radiologic review, treatment should not be discontinued until progression of disease has been 
determined by the ICR group unless the principal investigator believes it is in the best interest of 
the participant to discontinue treatment before receiving confirmation. 
For participants who discontinue treatment for reasons other than disease progression, every 
effort should be made to continue monitoring their disease status by radiographic imaging until 
the start of new anticancer therapy, documented disease progression, death, or the end of the 
study, whichever occurs first. 
8.2.2. 
ECOG Performance Status 
Eastern Cooperative Oncology Group performance status (see Table 9) will be assessed at the 
visits specified in Table 3. 


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Table 9: 
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. 
 
 
 
8.2.4. 
Medical Resource Utilization and Health Economics 
Medical resource utilization and health economics data, associated with medical encounters, may 
be assessed using data already captured in the eCRF for all participants in this study (eg, AEs, 
concomitant medications, procedures). 
The data collected may be used to conduct exploratory economic analyses and may include: 
• Number and duration of medical care encounters, including surgeries, and other 
selected procedures (inpatient and outpatient). 
• Duration of hospitalization (total days or length of stay, including duration by wards 
[eg, intensive care unit). 
• Number and type of diagnostic and therapeutic tests and procedures. 
• Outpatient medical encounters and treatments (including physician or emergency 
room visits, tests and procedures, and medications). 
8.3. 
Safety Assessments 
See Section 6.5 for guidelines regarding the management of relevant laboratory or other safety 
assessment abnormalities. 
8.3.1. 
Adverse Events 
Adverse events will be monitored from the time the participant signs the ICF until at least 
30 days after the last dose of study drug or until the start of new anticancer therapy. Adverse 
events for enrolled participants that begin or worsen after informed consent should be recorded 
on the Adverse Events Form in the eCRF regardless of the assumption of a causal relationship 
with the study drug. Conditions that were already present at the time of informed consent should 


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be recorded on the Medical History Form in the eCRF. Adverse events (including laboratory 
abnormalities that constitute AEs) should be described using a diagnosis whenever possible 
rather than by individual underlying signs and symptoms. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative). The investigator and any 
qualified designees are responsible for detecting, documenting, and recording events that meet 
the definition of an AE or SAE and remain responsible for following-up on AEs that are serious, 
considered related to the study drug/procedures, or that caused the participant to discontinue the 
study drug and/or withdraw from the study. Care will be taken not to introduce bias when 
detecting AEs and/or SAEs. Open-ended and nonleading verbal questioning of the participant, 
such as "How are you feeling?" is the preferred method to inquire about AE occurrences. 
Adverse events may also be detected when they are volunteered by the participant during the 
screening process or between visits or through physical examinations, laboratory tests, or other 
assessments. The definition, reporting, and recording requirements for AEs are described in 
Section 9. 
All SAEs will be reported to the sponsor or designee within 24 hours. The investigator will 
submit any updated SAE data to the sponsor within 24 hours of it being available. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
8.3.2. 
Physical Examinations 
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. Abnormalities identified after the first dose of study treatment constitute an AE if they 
are considered clinically meaningful, induce clinical signs or symptoms, require concomitant 
therapy, or require changes in study drug. Investigators should pay special attention to clinical 
signs related to previous serious illnesses. 
At the screening visit, a comprehensive physical examination should be conducted. The 
comprehensive physical examination will include height and body weight, and assessment 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. 
During the study, participants will be assessed by the investigator or medically qualified 
designee per institutional standard of care. These assessments should be an evaluation as 
indicated by participant symptoms, AEs, or other findings and documented on the AE eCRF. 
Weight will also be assessed at each study visit. 
8.3.3. 
Vital Signs 
Abnormal vital sign results identified after the first dose of study drug constitute an AE if they 
are considered clinically meaningful, induce clinical signs or symptoms, require concomitant 
therapy, or require changes in study drug/treatment. 


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Vital sign measurements should be taken before blood collection for laboratory tests and include 
blood pressure, pulse, respiratory rate, pulse oximetry, and body temperature. If vital signs 
cannot be taken before blood collection for laboratory tests, there must be a minimum of 
approximately 30 minutes from the completion of the blood collection procedures to the 
beginning of the vital signs collection. Blood pressure and pulse will be taken with the 
participant in the recumbent, semirecumbent, or sitting position after approximately 5 minutes of 
rest. 
8.3.4. 
Electrocardiograms 
Single 12-lead ECGs will be obtained as outlined in the SoA (see Table 3) using an ECG 
machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTcF 
intervals. All 12-lead ECGs will be performed with the participant 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 
participant management. Additional 12-lead ECGs may be performed as clinically indicated to 
manage participant safety. The decision to include or exclude a participant or discontinue study 
treatment 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. In the event that a single QTcF is > 480 milliseconds at screening, the 
participant may enroll if the average QTcF for 3 ECGs is ≤ 480 milliseconds or with approval 
from the medical monitor. For participants with an intraventricular conduction delay (QRS 
interval > 120 milliseconds) at screening, the JTc interval may be used in place of the QTcF with 
medical monitor approval. In addition, the JTc interval should be used for all subsequent 
assessments. 
8.3.5. 
Comprehensive Eye Examination 
A comprehensive eye examination must be performed by a qualified ophthalmologist at 
screening, once every 3 cycles (± 7 days, starting at Cycle 3), at EOT, and as clinically indicated. 
The eye examination must 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. 
Per CTCAE v 5.0, retinal detachment is graded as 3 (macular sparing) and 4 (macula‐off), but 
this refers to rhegmatogenous retinal detachment (when a hole occurs in the retina). There is no 
grading for SRD/RPED (no hole in the macula, just fluid accumulation). Therefore, grading 
should be based on the CTCAE v5.0 term of retinopathy. 
8.3.6. 
Laboratory Assessments 
See Table 10 for the list of clinical laboratory tests to be performed and Table 3 for the timing 
and frequency. A certified laboratory local to the investigative site will perform all clinical 
laboratory assessments for safety (ie, blood chemistries, hematology assessments, coagulation 
tests, endocrine function, serology assessments, and urinalysis). The investigative site will enter 
the laboratory results and laboratory normal ranges into the eCRF. Additional testing may be 


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required by the sponsor based on emerging safety data. Additional tests may also be performed if 
clinically indicated. 
Clinically significant abnormal laboratory findings are those that are not associated with the 
underlying disease, unless judged by the investigator to be more severe than expected for the 
participant's condition. All laboratory tests with values considered clinically significantly 
abnormal during participation in the study or within 30 days after the last dose of study treatment 
should be repeated until the values return to normal or baseline or are no longer considered 
clinically significant by the investigator or medical monitor. 
Screening laboratory assessments must be performed within 3 days before Cycle 1 Day 1. If 
performed more than 3 days before Cycle 1 Day 1, then the tests must be repeated and eligibility 
confirmed before study treatment administration on Cycle 1 Day 1. 


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Table 10: 
Required Laboratory Analytes 
Blood Chemistries  
Hematology  
Urinalysis With 
Microscopic Examination  
Serology 
Coagulation  
Albumin 
Alkaline phosphatase 
ALT 
AST 
Amylase 
Bicarbonate or CO 
Blood urea nitrogen or urea 
Calcium (uncorrected) 
Chloride 
Creatinine 
Glucose 
Lactate dehydrogenase 
Lipase 
Magnesium 
Phosphate 
Potassium 
Sodium 
Total bilirubin 
Direct bilirubin (if total bilirubin 
is elevated above ULN) 
Total protein 
Uric acid 
Urea 
Vitamin D (25-hydroxyvitamin D 
and 1, 25- dihidroxyvitamin D 
Complete blood count, 
including: 
• Hemoglobin 
• Hematocrit 
• Platelet count 
• Red blood cell count 
• WBC count 
 
Differential count, including: 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
Color and appearance 
pH and specific gravity 
Bilirubin 
Glucose 
Ketones 
Leukocytes 
Nitrite 
Occult blood 
Protein 
HB surface antigen 
HB surface antibody 
Hepatitis B core antibody 
HBV-DNA 
HCV antibody 
HCV-RNA 
HIV (if indicated) 
PT 
PTT or aPTT 
INR 
Endocrine Function 
Pregnancy Testing 
PTH 
hCG (serum and urine) 
Note: Additional tests may be required, as agreed upon by the investigator and sponsor, based on emerging safety data or to rule out a diagnosis. 


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8.3.6.1. 
Pregnancy Testing 
A serum pregnancy test will be required for all WOCBP during screening. Urine pregnancy tests 
will be performed locally on Day 1 of each cycle (before the first dose of study drug), at EOT, 
and at the safety follow-up visit as outlined in Table 3. Urine pregnancy tests will also be 
performed as medically indicated (eg, in case of loss of menstrual cycle, when pregnancy is 
suspected), or per country-specific requirement (note that country-required urine pregnancy 
testing will be outlined and communicated to investigational sites under separate cover). 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, the investigator will assess 
the potential benefit/risk to the participant and determine whether it is in the participant's best 
interest to resume study drug and continue participation in the study. 
If a pregnancy is confirmed by a serum pregnancy test, see Section 9.7 for reporting 
requirements. 
8.3.6.2. 
Serology 
Hepatitis screening assessments will be performed at the screening visit to rule out hepatitis 
infection; required analytes are shown in Table 10. Generally, hepatitis tests should be performed 
early in the screening process due to the length of time needed to obtain the results. Additional 
tests, including HIV testing, may be performed if appropriate and/or clinically indicated. 


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8.6. 
Unscheduled Visits 
Unscheduled visits may occur as clinically indicated. They can be used for visits that occur 
outside of visit windows and should be noted in the eCRF as an unscheduled visit. 
8.7. 
End of Treatment and/or Early Termination 
When the participant permanently discontinues study drug, whether the participant is terminating 
the study early or the participant has completed the study, the EOT visit should be conducted. If 
the EOT visit coincides with a regular study visit, the EOT evaluations will supersede those of 
that scheduled visit, and the data should be entered in the EOT visit in the eCRF. The participant 
should be encouraged to return for the follow-up visit. 
8.8. 
Follow-Up 
8.8.1. 
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 1) at least 
30 days after the last dose of study drug or the start of a new anticancer therapy or 2) until 
toxicities resolve, return to baseline, or are deemed irreversible, whichever is longer. Reasonable 
efforts should be made to have the participant return for the follow-up visit and report any AEs 
that may occur during this period. 
If a participant is scheduled to begin a new anticancer therapy before the end of the 30-day safety 
follow-up period, the safety follow-up visit should be performed before a new anticancer therapy 
is started. 
8.8.2. 
Post-Treatment Disease Follow-Up 
Participants who discontinue study drug for a reason other than disease progression will move 
into the disease status follow-up period and should be assessed every 12 weeks ± 7 days by 


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radiologic imaging to monitor disease status. Every effort should be made to collect imaging 
information regarding disease status until: 
• Disease progression. 
• Death. 
• The end of study. 
Continue to send all additional imaging tumor assessments for ICR review. 
8.8.3. 
Survival Follow-Up 
Once a participant has received the last dose of study drug, has confirmed disease progression, or 
starts a new anticancer therapy, the participant 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. 
For participants having entered the survival follow-up period of the study, the site will use 
continuing participant records to supply data on subsequent treatment regimens, tumor 
assessments (if discontinued treatment for a reason other than progression), and overall survival 
in the eCRF. For participants 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. 


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9. 
ADVERSE EVENTS: DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING 
9.1. 
Definition of Adverse Event 
Adverse Event Definition 
• An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or 
not it is considered drug-related. 
• An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. 
Additional Guidance for Events Meeting the Adverse Event Definition 
• Any safety assessments (eg, ECG, vital signs measurements), including those that worsen from 
baseline, considered clinically significant in the medical and scientific judgment of the investigator 
(ie, not related to progression of underlying disease) are to be reported as an AE. 
• Abnormal laboratory test results are to be reported as an AE if they are considered clinically 
meaningful, induce clinical signs or symptoms, require concomitant therapy, or require changes in 
study drug. Whenever possible, a diagnosis (eg, anemia, thrombocytopenia) should be recorded in 
the eCRF rather than the abnormal laboratory test result (eg, low hemoglobin, platelet count 
decreased). 
• Exacerbation of a chronic or intermittent pre-existing condition/disease, including either an increase 
in the frequency and/or intensity of the condition, is to be reported as an AE. 
• New conditions detected or diagnosed after the start of study drug administration are to be reported 
as an AE. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction are to be reported as 
an AE. 
• Signs and/or symptoms from dosing errors of a study drug (eg, overdose) or a concomitant 
medication are to be reported as an AE. 
• "Lack of efficacy," "disease progression," or "failure of expected pharmacological action" will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. 
• A condition that leads to a medical or surgical procedure (eg, endoscopy, appendectomy) will be 
reported as an AE if it occurs after obtaining informed consent. If the condition is present before 
entering the study, then it should be captured as medical history. 
• Pre-existing diseases or conditions with expected fluctuations in signs or symptoms should be 
reported as an AE only if the investigator judges the fluctuation to have worsened more than 
expected during study participation. 


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9.2. 
Definition of Serious Adverse Event 
If an event is not an AE per the definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death due 
to progression of disease). 
A serious adverse event is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term "life-threatening" in the definition of "serious" refers to an adverse drug experience that 
places the participant, in the opinion of the initial reporter, at immediate risk of death from the adverse 
experience as it occurs. This does not include an adverse drug experience that, had it occurred in a 
more severe form, might have caused death. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician's office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious. When in doubt as to whether hospitalization occurred or was necessary, the AE 
should be considered serious. 
Hospitalization for elective treatment or planned surgery (eg, stent replacement, hip surgery) is not 
considered an SAE. 
Hospitalization for medical interventions in which no unfavorable medical occurrence occurred 
(ie, elective procedures or routine medical visits) are not considered SAEs. 
d. Results in persistent or significant disability/incapacity 
• The term "disability" means a substantial disruption of a person's ability to conduct normal life 
functions. This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental 
trauma (eg, sprained ankle), that may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Is an important medical event 
An important medical event is an 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 participant and may require medical or surgical intervention to prevent 
one of the outcomes listed in the above definition. Examples of such events include new invasive or 
malignant cancers, intensive treatment in an emergency department or at home for allergic 
bronchospasm, blood dyscrasias, or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. Secondary malignancies should always be considered SAEs. 


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9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse 
Events 
Adverse Event and Serious Adverse Event Recording 
• An AE/SAE that begins or worsens after informed consent is signed should be recorded on the 
Adverse Event Form in the eCRF. AEs/SAEs should be reported for enrolled participants, but only 
SAEs need to be reported for screen failure participants. For enrolled participants, conditions that 
were present at the time informed consent was given should be recorded on the Medical History 
eCRF. For detailed information refer to the eCRF guidelines. 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(eg, hospital progress notes, laboratory reports, and diagnostic reports) related to the event. 
• The investigator (or delegate) will then record all relevant AE/SAE information in the eCRF. 
• It is not acceptable for the investigator to send photocopies of the participant's medical records 
in lieu of completing the Adverse Event Form in the eCRF. 
• There may be rare instances when copies of medical records for certain cases are requested. In this 
case, all participant identifiers, with the exception of the participant number, will be redacted by the 
site staff on the copies of the medical records before submission. These records can be submitted to 
Incyte Pharmacovigilance by email/fax per the contact information listed in the Study Reference 
Manual. 
• The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or 
other clinical information. Whenever possible, the diagnosis (not the individual signs/symptoms) will 
be documented as the AE/SAE. When a clear diagnosis cannot be identified, each sign or symptom 
should be reported as a separate AE/SAE. 
To the extent possible, each AE/SAE should be evaluated to determine the following: 
• The severity grade (CTCAE v5.0 [NCI 2017] Grade 1 to 5). See below for further instructions on the 
assessment of intensity. 
• Whether there is at least a reasonable possibility that the AE is related to the study drug: suspected 
(yes) or not suspected (no). See below for further instructions on the assessment of causality. 
• The start and end dates, unless unresolved at the final safety follow-up visit. 
• The action taken with regard to study drug as a result of the AE/SAE(s). 
• The event outcome. 
• The seriousness, as per the SAE definition provided in Section 9.2. 
• The action taken with regard to the event. Note: If an AE is treated with a concomitant medication or 
nondrug therapy, this action should be recorded on the Adverse Event Form and the treatment should 
be specified on the appropriate eCRF 


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Assessment of Intensity 
The severity of AEs will be assessed using CTCAE v5.0 Grades 1 through 5. 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. 
The investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to 1 of the following categories: 
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment 
not indicated. 
• Grade 2: Moderate; minimal, local, or noninvasive treatment 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 treatment indicated. 
• Grade 5: Fatal. 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study drug and each occurrence of 
each AE/SAE. 
• A "reasonable possibility" of a relationship conveys that there are medical facts, evidence, and/or 
arguments to suggest a causal relationship, rather than that a relationship cannot be ruled out. 
• The investigator will use clinical judgment to determine the possibility of a relationship. 
• The investigator will also consult the RSI in the IB for study drug in making his/her assessment. 
• Alternative causes, such as underlying or concurrent disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study drug administration, will be 
considered and investigated. 
• For each AE/SAE, the investigator must document in the medical notes that he/she has reviewed the 
AE/SAE and has provided an assessment of causality. 
• With regard to assessing causality of SAEs: 
− There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report. However, the causality assessment is one of the criteria 
used when determining regulatory reporting requirements. Therefore, it is very important that 
the investigator always make an assessment of causality based on the available information 
for every event before the initial transmission of the SAE. 
− The investigator may change his/her opinion of causality in light of follow-up information and 
submit the updated causality assessment. 


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Follow-Up of Adverse Events and Serious Adverse Events 
• The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the sponsor to elucidate the nature 
and/or causality of the AE or SAE as fully as possible. This may include additional laboratory tests 
or investigations, histopathological examinations, or consultation with other health care 
professionals. 
• Once an AE is detected, it should be followed in the AE eCRFs 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. 
• Updated SAE information will be recorded in the originally completed eCRF and reported to Incyte 
Pharmacovigilance (in the SAE EDC CRF) until resolution, stabilization, the event is otherwise 
explained, or the participant is lost to follow-up. 
• Any updated SAE data (including SAEs being downgraded to nonserious) will be submitted to the 
sponsor (or designee) within 24 hours of receipt of the information. 
See Appendix D for the management of potential Hy's law cases. 
9.4. 
Reporting of Serious Adverse Events 
Regardless of suspected causality (eg, relationship to study drug or study procedures), all SAEs 
occurring after the participant has signed the ICF through the last safety visit or at least 35 days 
after the last dose of study drug or until the participant starts a new anticancer therapy must be 
reported to the sponsor (or designee) immediately, without undue delay but not later than within 
24 hours of obtaining knowledge of its occurrence unless otherwise specified by the Protocol. 
The investigator will submit any updated SAE data to the sponsor (or designee) immediately, 
without undue delay but not later than within 24 hours of it being available. 
Investigators are not obligated to actively seek SAE information after the safety follow-up visit 
or 35 days after the last dose of study drug. If the investigator learns of any SAE, including 
death, at any time during this period, and he/she considers the event to be reasonably related to 
the study drug or study participation, then the investigator must notify the sponsor (or designee) 
within 24 hours of becoming aware of the event. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
Prompt notification by the investigator to the sponsor regarding an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a study 
drug under clinical investigation are met. 
If the SAE is not documented in the RSI of the IB for the study drug (new occurrence) and is 
thought to be related to the study drug, the sponsor or its designee may urgently require further 
information from the investigator for expedited reporting to health authorities. The sponsor or its 
designee may need to issue an Investigator Notification to inform all investigators involved in 
any study with the same drug that this SAE has been reported. Suspected unexpected serious 


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adverse reactions 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. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study drug under clinical investigation. The sponsor 
will comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB/IEC, and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and sponsor policy and forwarded to investigators as 
necessary. 
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate, according to local requirements. 
Serious Adverse Event Reporting 
• Information about all SAEs is collected and recorded on the Adverse Event Form in the eCRF. 
• The investigator must report within 24 hours of learning of its occurrence any SAE via the EDC 
system (primary method) or by completing the Serious Adverse Event Report Form in English (only 
if the EDC system is not available. The contact information for Incyte Pharmacovigilance by 
email/fax is listed in the Study Reference Manual). 
• In circumstances where the EDC system is not accessible for reporting SAE information (initial 
and/or follow-up SAE information) to the sponsor within 24 hours, refer to the Incyte Reference 
Guide for Completing the Serious Adverse Report Form. Once the EDC system is functional, the 
SAE report should be retrospectively added to the EDC system and follow-up should be completed 
through the EDC. The original copy of the Serious Adverse Event Report Form and the email or 
facsimile confirmation sheet must be kept at the study site (refer to the Incyte Reference Guide for 
Completing the Serious Adverse Report Form or Study Reference Manual for details and for the 
email address or fax number). 
• Follow-up information is also recorded in the eCRF and transmitted to Incyte Pharmacovigilance via 
the EDC system. The follow-up report should include information that was not provided previously, 
such as the outcome of the event, treatment provided, action taken with study drug because of the 
SAE (eg, dose reduced, interrupted, or discontinued), or participant 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. 
9.5. 
Events of Clinical Interest 
Not applicable. 
9.6. 
Emergency Unblinding of Treatment Assignment 
Not applicable. 


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9.7. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE unless there is suspicion that the study drug 
may have interfered with the effectiveness of a contraceptive medication or method. When a 
pregnancy has been confirmed in a participant during maternal or paternal exposure to study 
drug, the following procedures should be followed in order to ensure safety: 
• The study treatment must be interrupted immediately (female participants only). 
• If the female participant is no longer pregnant and meets the treatment continuation 
criteria within 14 days of the scheduled start of a cycle, study treatment may be 
resumed after approval has been received from the sponsor medical monitor. 
• 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 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 or Study Reference Manual. 
Any SAE occurring during pregnancy of a study participant must be recorded on the 
Serious Adverse Event Report Form and submitted to the sponsor or its designee. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, or ectopic pregnancy) are considered SAEs (if occurring in the study participant) and 
must be reported as described in Section 9.4. If an abnormal pregnancy outcome is reported in a 
study participant's partner, the event should be reported to the sponsor on the Clinical Trial 
Pregnancy Form. 
9.8. 
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. Any 
important new safety information should be discussed with the participant during the study as 
necessary. If new significant risks are identified, they will be added to the ICF. 
9.9. 
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. 


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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 recorded as described in Section 9.3. 
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. 
9.10. 
Treatment of Overdose 
There has been no clinical experience with overdose of pemigatinib. Treatment of overdose 
should consist of general supportive measures. 


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10. 
STATISTICS 
10.1. 
Sample Size Determination 
Approximately 125 participants with select FGFR alterations are planned for the final analysis of 
the endpoint of ORR. With the assumed rates of 40% for pemigatinib, a sample size of 
approximately 100 participants would provide about > 95% probability to have a 95% CI with 
lower limit of > 20%. Up to 25 participants will be enrolled in Cohort B, which will provide 
> 80% chance of observing at least 3 responders in this cohort if the underlying ORR is 20%. 
10.2. 
Populations for Analyses 
Table 13 presents the populations for analysis. 
Table 13: 
Populations for Analysis 
Population 
Description 
Full analysis set 
The full analysis set includes all enrolled participants who received at least 
1 dose of pemigatinib. 
The full analysis set will be used for the summary of demographics, baseline 
characteristics, participants disposition, and analyses of all efficacy data,  
Safety 
The safety population includes all enrolled participants who received at least 
1 dose of pemigatinib. 
All safety analyses will be conducted using the safety population.  
Per protocol  
Participants in the full analysis set who are considered to be sufficiently 
compliant with the Protocol comprise the per protocol population. 
RECIST evaluable 
The RECIST evaluable population includes all participants in full analysis set 
who have at least 2 objective tumor response assessments per ICR review or who 
withdrew from the study or discontinued treatment without post-treatment tumor 
assessments. 
10.3. 
Level of Significance 
All CIs will be provided at a 95% confidence level. 
10.4. 
Statistical Analyses 
10.4.1. 
Primary Analysis 
The primary endpoint of the study is ORR in Cohort A, defined as the proportion of participants 
who achieve a CR or PR based RECIST v1.1 as assessed by an ICR review. The primary 
analysis of ORR will be based on the full analysis set. Participants 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 the per protocol population as sensitivity analysis. 


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10.4.2. 
Secondary Analysis 
Secondary efficacy analysis will be conducted for the full analysis set. 
Objective response rate in Cohort B is defined as the proportion of participants who achieve a 
CR or a PR based RECIST v1.1 as assessed by an ICR review. Participants 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. 
Progression-free survival is defined as the time from the date of first dose of pemigatinib to the 
date of the first documented progressive disease or death due to any cause, whichever is first. 
Progressive disease will be evaluated according to RECIST v1.1 and assessed by an ICR review. 
Participants who are alive without progression before the analysis cut-off date will be censored. 
Censoring for PFS will follow the algorithm based on FDA guidance (FDA 2007). 
Progression-free survival data will be analyzed by the Kaplan-Meier method. 
For objective responders, DOR is defined as the time from the date that a participant first 
achieves CR or PR, until the date of first documented progressive disease or death, whichever is 
first. Responses and progressive disease will be evaluated based on RECIST v1.1 by an ICR 
review. Participants 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. 
Overall survival is defined as the time from the date of first dose of pemigatinib to the date of 
death due to any cause. Participants 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. 
10.4.3. 
Safety Analyses 
Safety analyses will be conducted for the safety population. Adverse events will be coded by the 
MedDRA dictionary, and TEAEs (ie, AEs reported for the first time or worsening of a 
pre-existing event after first dose of pemigatinib and within 30 days of last dose of pemigatinib) 
will be tabulated by preferred term and system organ class for all events, related events, and 
events of Grade 3 or higher according to NCI CTCAE v5.0, and events leading to dose 
interruption, dose reduction, and study treatment discontinuation. Quantitative safety variables 
(eg, laboratory values, vital signs) and their changes from baseline will be summarized with 
descriptive statistics. Clinically notable abnormal values will be flagged and tabulated based on 
predefined criteria. 
The clinical laboratory data will be analyzed using summary statistics. In addition, distributions 
of key laboratory parameters may be plotted over time; these values will also be classified into 
CTCAE v5.0 toxicity grades, and tabulated. 
Descriptive statistics and mean change from baseline will be determined for vital signs and each 
ECG parameter at each assessment time. Vital sign and ECG results will be reviewed for 
clinically notable abnormalities. Participants exhibiting clinically notable ECG abnormalities 
will be listed. 
Measures of exposure of pemigatinib will be summarized by means of summary statistics. 


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10.5. 
Interim Analysis 
A futility analysis will be performed when approximately 25 participants are enrolled into 
Cohort A and have at least 2 objective tumor response assessments per ICR review or are 
withdrawn from the study or discontinued from treatment without post-treatment tumor 
assessments. Cohort A can be stopped for futility if ≤ 6 responders are observed in the RECIST 
evaluable population, for which there is < 15% probability of claiming ORR > 20% at final 
analysis. This rule is just a guidance and nonbinding. 


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11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
11.1. 
Investigator Responsibilities 
• The Protocol, Protocol amendments, ICF, IB, and other relevant documents 
(eg, advertisements) must be submitted to an IRB/IEC by the investigator and 
reviewed and approved by the IRB/IEC and Health Authorities, before the study is 
initiated. 
• The investigator is responsible for ensuring that the safety reports provided by the 
sponsor are reviewed and processed in accordance with regulatory requirements, the 
policies and procedures established by the IRB/IEC, and institutional requirements. 
• Any amendments to the Protocol will require approval from both Health Authorities 
and IRB/IEC before implementation of changes made to the study design, except for 
changes necessary to eliminate an immediate hazard to study participants. 
• The investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC. 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
− Providing oversight of the conduct of the study at the site and adherence to GCP, 
IRB/IEC requirements, institutional requirements, and applicable laws and 
country-specific regulations. 
• 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 participants 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. 


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− 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. 
11.1.1. 
Identification of the Coordinating Principal Investigator 
A coordinating principal investigator will be appointed by the sponsor before the end of the 
study. As part of his or her responsibilities, the coordinating principal investigator will review 
the final CSR. Agreement with the final CSR will be documented by the dated signature of the 
coordinating principal investigator. 
11.2. 
Data Management 
Data management will be performed in a validated EDC system. The investigator will be 
provided with access to an EDC system so that an eCRF can be completed for each participant. 
The site will be provided with eCRF completion guidelines for instructions on data entry in 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. Other data outside the EDC system required in the study conduct of 
the Protocol such as documents or results transmitted to the sponsor via a central laboratory or 
specialized technical vendors and, as designated by the sponsor, will have their own data flow 
management plans, study charters, 
 as applicable. 
The sponsor (or designee) will be responsible for: 
• Managing the integrity of the data and the quality of the conduct of the study, such as 
ensuring that study monitors perform ongoing source data verification to confirm that 
data entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved Protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• Managing and reconciling the data generated, and/or collected including documents 
and results such as laboratory or imaging data analyzed centrally by a designated 
vendor of the sponsor. 
The investigator will be responsible for: 
• Recording, or ensuring the recording of, all relevant data relating to the study in the 
eCRF. 
• Delivering, or ensuring the delivery of, all other results, documents, data, know-how, 
or formulas relating to the study to the sponsor or designee electronically and/or 
centrally (eg, laboratory data, imaging data, 
 photographs, diary data), 
or as otherwise specified in the Protocol. 


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• Maintaining adequate and accurate source documents and trial records that include all 
pertinent observations on each of the site's trial participants. Source data should be 
attributable, legible, contemporaneous, original, accurate, and complete. Changes to 
source data should be traceable, should not obscure the original entry, and should be 
explained if necessary (eg, via an audit trail). Source data are, in general, all 
information in original records and certified copies of original records of clinical 
findings, observations, or other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial. Source data are contained in source 
documents (original records or certified copies). 
• Verifying that data entries are accurate and correct by physically or electronically 
signing the eCRF. 
• Maintaining accurate documentation (source data) that supports the information 
entered in the eCRF, or sent to a central vendor designated by the sponsor, or as 
described in other study and data flow manuals. 
− Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed and 
available at the investigator's site. Examples of source documents are original 
documents, data, and records (eg, hospital records, electronic hospital records, 
clinical and office charts, laboratory notes, memoranda, participants' diaries or 
evaluation checklists, pharmacy dispensing records, recorded data from 
automated instruments, copies or transcriptions certified after verification as being 
accurate copies, microfiches, photographic negatives, microfilm or magnetic 
media, x-rays, participants' files, and e-records/records kept at the pharmacy, at 
the laboratories and at medico-technical departments involved in the clinical 
trial). 
− Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, 
depending on the study. Current applicable medical records must be available. 
• Sending participants' data, either as unique samples, or copies, or photographs, to be 
evaluated centrally or analyzed centrally, or both, by a qualified vendor designated by 
the sponsor. 
• 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 
participant records at each monitoring visit. 


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− 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 participants. 
− 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. 
11.3. 
Data Privacy and Confidentiality of Study Records 
The investigator and the sponsor or its designee must adhere to applicable data protection laws 
and regulations. The investigator and the sponsor or its designee are responsible for ensuring that 
sensitive personal information is handled in accordance with local data protection laws 
(including but not limited to HIPAA and GDPR) as applicable. Appropriate consent for 
collection, use and disclosure and/or transfer (if applicable) of personal information must be 
obtained in accordance with local data protection laws. 
Participant names will not be supplied to the sponsor or its designee. Only the participant 
number will be recorded in the eCRF; if the participant'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 
appropriate technical and organizational measures as required by local data protection laws. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for 10 years after study completion unless local regulations require 
otherwise. No records may be destroyed during the retention period without the written approval 
of the sponsor. No records may be transferred to another location or party without written 
notification to the sponsor. 
11.4. 
Financial Disclosure 
Before study initiation, all clinical investigators participating in clinical studies subject to FDA 
Regulation Title 21 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 participants, 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 


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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. 
11.5. 
Publication Policy 
By signing the study Protocol, the investigator and his/her institution agree that the results of the 
study may be used by the sponsor, Incyte Corporation, 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. 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission. 
This allows the sponsor to protect proprietary information and to provide comments. 
The sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined in line with International Committee of Medical Journal Editors 
authorship requirements. 
11.6. 
Study and Site Closure 
The sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the Protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines. 
• Inadequate recruitment of participants by the investigator. 
• Discontinuation of further study treatment development. 


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12. 
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Balversa (erdafitinib) [prescribing information]. Janssen Pharmaceutical Companies; April 2020. 
Campbell JD, Alexandrov A, Kim J, et al. Distinct patterns of somatic genome alterations in lung 
adenocarcinomas and squamous cell carcinomas. Nat Genet 2016;48:607-616. 
Chantharasamee J, Poungvarin N, Danchaivijitr P, Techawatanawanna S. Clinical outcome of 
treatment of metastatic non-small cell lung cancer in patients harboring uncommon EGFR 
mutation. BMC Cancer 2019;19:701. 
Clinical Trials Facilitation and Coordination Group. Recommendations related to contraception 
and pregnancy testing in clinical trials. 2020. 
Dailey L, Ambrosetti D, Mansukhani A, Basilico C. Mechanisms underlying differential 
responses to FGF signaling. Cytokine Growth Factor Rev 2005;16:233-247. 
Dela Cruz CS, Tanoue LT, Matthay RA. Lung cancer: epidemiology, etiology, and prevention. 
Clin Chest Med 2011;32:605-644. 
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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. 
European Medicines Agency. Guidance on the Management of Clinical Trials During the 
COVID-19 (Coronavirus) Pandemic. 2020. 
EuroQol Group. EuroQol--a new facility for the measurement of health-related quality of life. 
Health Policy 1990;16:199-208. 
Farrow EG, White KE. Recent advances in renal phosphate handling. Nat Rev Nephrol 
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Fennell DA, Summers Y, Cadranel J, et al. Cisplatin in the modern era: the backbone of first-line 
chemotherapy for non-small cell lung cancer. Cancer Treat Rev 2016;44:42-50. 
Food and Drug Administration. Guidance for Industry: Clinical Trial Endpoints for the Approval 
of Cancer Drugs and Biologics. 2007. 
 
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 
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Global Cancer Observatory. GLOBOCAN 2020. Accessed October 11, 2021. https://gco.iarc.fr 
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. 
Helsten T, Elkin S, Arthur E, Tomson BN, Carter J, Kurzrock R. The FGFR Landscape in 
cancer: analysis of 4,853 tumors by next-generation sequencing. Clin Cancer Res 
2016;22:259-267. 
Itoh N. Hormone-like (endocrine) FGFs: their evolutionary history and roles in development, 
metabolism, and disease. Cell Tissue Res 2010;342:1-11. 
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J 
Clin 2011;61:69-90. 
Keytruda (pembrolizumab) [prescribing information]. Merck & Co., Inc; August 2021. 
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. 
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Used?. Cancers (Basel) 2019;11:366. 
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lung cancer. Eur J Cancer 2019;108:120-128. 
Nakamura H, Arai Y, Totoki Y, et al. Genomic spectra of biliary tract cancer. Nat Genet 
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5.0. 2017. 
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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. 
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Rades D, Setter C, Dahl O, Schild SE, Noack F. Fibroblast growth factor 2--a predictor of 
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APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS AND DEFINITIONS 
Definitions 
WOCBP: A woman who is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below) 
Women in the following categories are not considered WOCBP: 
• Premenarchal 
• Premenopausal with 1 of the following:a 
− Documented hysterectomy 
− Documented bilateral salpingectomy 
− Documented bilateral oophorectomy 
• Postmenopausal 
− A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. 
o A high FSH level in the postmenopausal range may be used to confirm a postmenopausal state in 
women not using hormonal contraception or HRT. However, in the absence of 12 months of 
amenorrhea, confirmation with 2 FSH measurements in the postmenopausal range is required. 
− Females on HRT and whose menopausal status is in doubt will be required to use 1 of the nonhormonal, 
highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, 
they must discontinue HRT to allow confirmation of postmenopausal status before study enrollment. 
For male participants of reproductive potentialb 
The following methods during the Protocol-defined timeframe in Section 5.1 are highly effective: 
• Use of a male condom plus partner use of an additional contraceptive method when having penile-vaginal 
intercourse with a woman of childbearing potential who is not currently pregnant 
• Vasectomy with medical assessment of the surgical success (verified by site personnel's review of the 
participant's medical records) 
• Sexual abstinencec 
− Abstinence from penile-vaginal intercourse 
The following are not acceptable methods of contraception: 
• Periodic abstinence (calendar, symptothermal, postovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhoea method 
• Male condom with cap, diaphragm, or sponge with spermicide 
• Male and female condom used together 
Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal 
intercourse or use a male condom during each episode of penile penetration.  


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For female participants who are WOCBP 
The following methods during the Protocol-defined timeframe in Section 5.1 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: 
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulation.d 
− oral 
− intravaginal 
− transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulationd 
− oral 
− injectable 
− implantablee 
• Intrauterine devicee 
• Intrauterine hormone-releasing systeme 
• Bilateral tubal occlusione 
• Vasectomized partnere,f 
• Sexual abstinencec  
a Documentation can come from the site personnel's review of the participant's medical records, medical examination, or medical 
history interview. 
b If the male participant has a partner with childbearing potential the partner should also use contraceptives. 
c 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 study and the preferred and usual lifestyle of the 
participant. 
d Hormonal contraception may be susceptible to interaction with the investigational medicinal product, which may reduce the 
efficacy of the contraception method. Two methods of contraception should be used. 
e Contraception methods that in the context of this guidance are considered to have low user dependency. 
f Vasectomized partner is a highly effective method of avoiding pregnancy provided that partner is the sole sexual partner of the 
WOCBP study participant and that the vasectomized partner has received medical assessment of the surgical success. 
Source: Clinical Trials Facilitation and Coordination Group (2020). 


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APPENDIX B. FGF/FGFR TESTING AND ALTERATIONS 
Screening should be performed using the investigative site genomics assay per institutional 
standard procedures. If FMI/Foundation One is not used as part of standard genomic screening 
practice, local tests may include FISH (eg, FGFR2 fusion) or non-NGS tests (eg, Therascreen 
FGFR RGQ RT-PCR). Blood cfDNA/ctDNA results from Guardant 360 or Foundation One 
liquid tests are eligible for enrollment as well. Participants enrolled using local genomics results 
will submit tumor tissue to the sponsor's central lab for confirmation of FGFR1-3 actionable 
alterations. 
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. 
Known/Likely Actionable Mutations of FGFR1-3 
Gene 
Alteration 
Position 
Gene 
Alteration 
Position 
Gene 
Alteration 
Position 
FGFR1 
R189C 
189 
FGFR2 
A315S 
315 
FGFR3 
A391E 
391 
FGFR1 
P252R 
252 
FGFR2 
C342F 
342 
FGFR3 
G342C 
342 
FGFR1 
Y372C 
372 
FGFR2 
C342G 
342 
FGFR3 
G370C 
370 
FGFR1 
Y374C 
374 
FGFR2 
C342R 
342 
FGFR3 
G375C 
375 
FGFR1 
C379R 
379 
FGFR2 
C342S 
342 
FGFR3 
G380R 
380 
FGFR1 
C381R 
381 
FGFR2 
C342W 
342 
FGFR3 
R200C 
200 
FGFR1 
R445W 
445 
FGFR2 
C342Y 
342 
FGFR3 
R248C 
248 
 
 
 
FGFR2 
C382R 
382 
FGFR3 
S249C 
249 
 
 
 
FGFR2 
C382Y 
382 
FGFR3 
S371C 
371 
 
 
 
FGFR2 
D336G 
336 
FGFR3 
Y373C 
373 
 
 
 
FGFR2 
M391R 
391 
 
 
 
 
 
 
FGFR2 
P253F 
253 
 
 
 
 
 
 
FGFR2 
P253L 
253 
 
 
 
 
 
 
FGFR2 
P253R 
253 
 
 
 
 
 
 
FGFR2 
R203C 
203 
 
 
 
 
 
 
FGFR2 
R210Q 
210 
 
 
 
 
 
 
FGFR2 
S252F 
252 
 
 
 
 
 
 
FGFR2 
S252W 
252 
 
 
 
 
 
 
FGFR2 
S267P 
267 
 
 
 
 
 
 
FGFR2 
S347C 
347 
 
 
 
 
 
 
FGFR2 
S351C 
351 
 
 
 
 
 
 
FGFR2 
S354C 
354 
 
 
 
 
 
 
FGFR2 
S372C 
372 
 
 
 
 
 
 
FGFR2 
V395D 
395 
 
 
 
 
 
 
FGFR2 
W290C 
290 
 
 
 
 
 
 
FGFR2 
Y375C 
375 
 
 
 


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APPENDIX C. INSTRUCTION TO PARTICIPANTS FOR HANDLING 
STUDY DRUG 
The participant must be instructed in the handling of study drug as follows: 
• Store study drug at room temperature (15-30°C). 
• Only remove the number of tablets needed at the time of administration. 
• Do not remove doses in advance of the next scheduled administration. 
• Make every effort to take doses on schedule. 
• Report any missed doses/lost tablets. 
• Take study drug with a full glass of water. 
• If vomiting occurs after taking study drug, do not take another dose. 
• Keep study drug in a safe place and out of reach of children. 
• Bring all used and unused study drug bottles/kits to the site at each visit. 
• If a dose of pemigatinib is missed by more than 4 hours, that dose should be skipped 
and the next scheduled dose should be administered at the usual time. 


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APPENDIX D. MANAGEMENT OF POTENTIAL HY'S LAW CASES 
INTRODUCTION 
During the course of the study, the investigator will remain vigilant for increases in liver 
biochemistry. The investigator is responsible for determining whether a participant meets PHL 
criteria at any point during the study. 
The investigator participates, in conjunction with Incyte clinical project and pharmacovigilance 
representatives, in the review and assessment of cases fulfilling PHL criteria to ascertain whether 
there is an alternative explanation for the elevations in liver biochemistry other than 
drug-induced liver injury caused by the study drug. 
The investigator fulfills requirements for the recording of data pertaining to PHL or Hy's law 
cases and AE/SAE reporting according to the outcome of the review and assessment in line with 
standard safety reporting processes. 
DEFINITIONS 
For the purpose of this process, definitions are as follows: 
Potential Hy's Law 
An increase in AST or ALT > 3 × ULN and total bilirubin > 2 × ULN at any point during the 
study. The elevations do not have to be at the same time or within a specified timeframe. 
Hy's Law 
An increase in AST or ALT ≥ 3 × ULN and total bilirubin > 2 × ULN, where no other reason can 
be found to explain the combination of increases (eg, elevated serum ALP indicating cholestasis, 
viral hepatitis, another drug). 
ACTIONS REQUIRED IN CASES OF AST OR ALT > 3 × ULN OR TOTAL BILIRUBIN 
≥ 2 × ULN 
Identification and Determination of Potential Hy's Law 
To identify cases of AST or ALT > 3 × ULN or total bilirubin > 2 × ULN and consequently 
determine whether the participant meets PHL criteria, please follow the instructions below: 
• Review the laboratory report and if a participant has AST or ALT > 3 × ULN OR 
total bilirubin > 2 × ULN at any visit: 
− Determine without delay whether the participant meets PHL criteria by reviewing 
laboratory reports from all previous visits. 
− Enter the laboratory data into the laboratory eCRF as soon as possible. 


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Potential Hy's Law Criteria Not Met 
If the participant has NOT had AST or ALT ≥ 3 × ULN AND total bilirubin > 2 × ULN at any 
point in the study (the elevations do not have to be at the same time or within a specified 
timeframe), irrespective of ALP, please follow the instruction below: 
• Perform follow-up on subsequent laboratory results according to the guidance 
provided in Section 6.5.1. 
Potential Hy's Law Criteria Met 
If the participant has had AST or ALT ≥ 3 × ULN AND total bilirubin > 2 × ULN at any point in 
the study (the elevations do not have to be at the same time or within a specified timeframe), 
irrespective of ALP, please follow the instruction below: 
• Have participant interrupt study drug. 
• Notify Incyte study team without delay. 
− The investigator, or designee, should contact the medical monitor to discuss and 
agree upon an approach for the study participant's follow-up and the continuous 
review of data. 
• Monitor the participant until liver biochemistry parameters and appropriate clinical 
symptoms and signs return to normal or baseline levels, or as medically indicated. 
• Investigate the etiology of the event and perform any relevant diagnostic 
investigations as discussed with the medical monitor. 
• Enter the laboratory data into the laboratory CRF as soon as possible. 
• If at any time (in consultation with the medical monitor) the PHL case meets serious 
criteria, report it as an SAE using standard reporting procedures. 
REVIEW AND ASSESSMENT 
No later than 3 weeks after the biochemistry abnormality is initially detected and the criteria for 
PHL is met, the medical monitor, Incyte pharmacovigilance physician, and investigator will 
discuss and review available data and agree on whether there is an alternative explanation for the 
elevations in liver biochemistry other than drug-induced liver injury caused by the study drug. 
Participant matter experts will be included in the review as appropriate. 


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Evaluation of Alternative Causes 
In order to gather additional clinical information to seek other possible causes of the observed 
liver test abnormalities, the following alternative etiologies should be considered, including but 
not limited to: 
• Active viral hepatitis 
• Alcoholic and autoimmune hepatitis 
• Hepatobiliary disorders 
− Biliary tract disease, such as migration of gallstones or intrahepatic lesions, more 
often causes cholestatic injury initially and should be investigated with gall 
bladder and ductal imaging studies, especially if alkaline phosphatase is 
increased. Malignant interruption of the biliary tract also should be considered. 
• Concomitant treatment 
• Other causes such as systemic infections (eg, bacterial, fungal, viral), nonalcoholic 
steatohepatitis, and cardiovascular diseases 
Actions After Review and Assessment 
According to outcome of the review and assessment, please follow the instructions below: 
If there is an agreed alternative explanation for the AST or ALT and total bilirubin elevations, a 
determination of whether the alternative explanation is an AE will be made and subsequently 
whether the AE meets the criteria for an SAE. 
• If the alternative explanation is not an AE, record the alternative explanation on the 
appropriate CRF if possible. 
• If the alternative explanation is an AE/SAE, record the AE/SAE in the eCRF 
accordingly and follow the standard study processes. 
• Have participant resume study drug as per Protocol guidelines. 
If it is agreed that there is no explanation that would explain the AST or ALT and total bilirubin 
elevations: 
• Have participant permanently discontinue study drug and perform end-of-treatment 
procedures. 
• Report an SAE (report term "Hy's Law"). 
− The 'medically important' serious criterion should be used if no other serious 
criteria apply. 
− As there is no alternative explanation for the Hy's law case, a causality assessment 
of related should be assigned. 
• If there is an unavoidable delay of over 3 weeks in obtaining the information 
necessary to assess whether or not the case meets the criteria for a Hy's law case, then 
it is assumed that there is no alternative explanation until such time as an informed 
decision can be made. Report an SAE (report term "Potential Hy's Law") applying 
serious criteria and causality assessment as per above. 


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ACTIONS REQUIRED FOR REPEAT EPISODES OF AST OR ALT > 3 × ULN AND/OR 
TOTAL BILIRUBIN > 2 × ULN 
The requirement to conduct follow-up, review, and assessment of a repeat occurrence(s) of PHL 
is based on the nature of the alternative cause identified for the previous occurrence. 
If the alternative cause for the previous occurrence of PHL was not chronic or progressing 
malignant disease, please follow the process for PHL review and assessment as described in this 
appendix. 
If the alternative cause for the previous occurrence of PHL was chronic or progressing malignant 
disease, please follow the instructions below: 
• Determine whether there has been a significant change* in the participant's condition. 
− If there is no significant change, no action is required. 
− If there is a significant change, follow the process described for PHL review and 
assessment as described in this appendix. 
* A 'significant' change in the participant's condition refers to a clinically relevant change in ALT, AST, or total 
bilirubin, or associated symptoms. The determination of whether there has been a significant change will be at the 
discretion of the investigator; this may be in consultation with the medical monitor if there is any uncertainty. 


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APPENDIX E. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS 
The COVID-19 global pandemic presents numerous challenges to the ongoing conduct of 
clinical trials. In line with the European Medicines Agency's Guidance on the Management of 
Clinical Trials During the COVID-19 (Coronavirus) Pandemic (2020), the sponsor has issued the 
following Protocol considerations to ensure participant safety is maintained and adequate 
benefit/risk analyses are applied relative to the completion of study procedures and maintaining 
the investigational product supply chain. 
Recognizing the flexibility required to manage the impact of the pandemic on this clinical trial, 
additional details will be added to respective study manuals and project plan documents and 
communicated to the investigative sites as needed. 
Study-Site Visits 
If local travel restrictions, isolation requirements, or the investigator's benefit/risk assessment 
determines it to be unsafe for participants to attend study visits at the investigational site, the site 
staff may elect to pursue the following: 
• In order to minimize participantt risk, study visits may be conducted via telemedicine 
modalities (phone or video). At a minimum, a review of AEs, concomitant 
medications, and study drug compliance must be completed. Periodic on-site visits 
should be conducted whenever feasible. 
• In order to support investigator oversight of participant safety and disease 
management, the participant may be asked to undergo some laboratory tests or study 
procedures (eg, eye exam) in a local (proximate) hospital laboratory or facility closer 
to the participant's residence rather than at the investigational site. In this case, the 
study physician will provide the participant with the list of parameters to be checked. 
These tests should be performed in certified laboratories. 
• Assessments that are missed should be noted as deviations to the Protocol and should 
be documented accordingly. 
Investigational Medicinal Product Dispensation and Distribution 
In order to ensure the continuity of providing their participant's clinical supplies within the 
constraints imparted by the pandemic, the site staff can decide to supply IMP to participants as 
follows: 
• Where possible, when the participant attends a visit at the study site, the investigator 
can dispense an additional amount of pemigatinib tablets to cover a longer interval 
between on-site study visits than stipulated in the SoA (see Table 3). 
• Alternatively, if the participant cannot attend a visit at the study site, adequate 
supplies of IMP to cover 1 or more cycles can be shipped to the participant by the 
investigator or appropriately delegated staff (eg, the study pharmacy staff) using a 
third-party service if duly authorized by the participant. The study site may use their 
own preferred courier, provided the courier adheres to certain standards (eg, use of 
personal protection equipment, maintenance of temperature-controlled transit 
environment), or one centrally contracted by the sponsor. 


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Clinical Trial Monitoring 
Study monitoring visits could be postponed; however, the site monitor will continue to employ 
off-site monitoring practices such as routine communication methods (eg, phone calls, emails, 
video visits) with the sites to get information on trial progress, participant status, and information 
on issue resolution. The study monitor may remotely review data entered into the EDC for 
accuracy and completeness. Remote source data verification may be implemented with 
agreement of the principal investigator and institution, as applicable. 
If the study site monitor cannot be on-site to perform the final drug accountability for 
reconciliation purposes, and the operation cannot be postponed, it may be performed by a 
pharmacist from the hospital pharmacy or by the study coordinator/data manager with suitable 
training. The IMP can be returned to the sponsor by the hospital pharmacy directly, or destroyed 
in accordance with local practices, if applicable, and with sponsor approval. 
Direct Contracts With Third Parties/Specialized Service Companies 
If necessary, direct contracts can be established with third-party local physicians to conduct 
activities related to the clinical management of participants for whom the investigator is 
responsible and maintains oversight. In such situations, the investigator is required to provide the 
local physician with a delegation letter listing all delegated activities. The sponsor, through the 
study investigator or institution, will reimburse the local physician for the test/procedures 
conducted outside of the standard of care. 
Reimbursement of Extraordinary Expenses 
The sponsor will arrange to reimburse participants for any extraordinary expenses, keeping 
appropriate documentation as evidence (eg, travel expenses for the local laboratory visit[s], the 
costs of local [proximate] laboratory tests). 


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APPENDIX F. CYP3A4 INHIBITORS AND INDUCERS 
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 John's 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  
Food products 
Conivaptan 
Diuretics 
Nefazodone 
Antidepressants 
Nelfinavir 
Protease inhibitors 
Saquinavir 
Protease inhibitors 
Ribociclib 
Kinase inhibitors 
Idelalisib 
Kinase inhibitors 
Boceprevir 
Antivirals 


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Inhibitor 
Therapeutic Class 
Moderate CYP3A Inhibitors  
Erythromycin 
Antibiotics 
Fluconazole 
Antifungals 
Atazanavir/RIT 
Protease inhibitors 
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 G. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Document 
Date 
Amendment 1 
08 DEC 2021 
Amendment 1 (08 DEC 2021) 
Overall Rationale for the Amendment: 
The primary purpose of the amendment is to implement updates based on feedback from the 
FDA. Additional changes are summarized below. 
1. Section 1, Protocol Summary (Table 2: Key Study Design Elements; Figure 1: Study 
Design Schema; Table 3: Schedule of Activities); Section 2.2.2, Justification for 
Dose; Section 4.1, Overall Study Design; Section 4.2, Overall Study Duration; 
Section 6, Study Treatment; Section 6.1, Study Treatment Information 
(Table 6: Study Treatment Information); Section 6.5.1, Criteria and Procedures for 
Dose Interruptions and Adjustments of Study Drug (Table 7: Guidelines for 
Interruption and Restarting of Study Drug) 
Description of change: Treatment administration changed from continuous dosing to 
intermittent dosing. 
Rationale for change: To address feedback from the FDA. 
2. Section 5.2, Exclusion Criteria (Criterion 19); Section 6.6.1, Restricted Medications 
and Procedures 
Description of change: Updated with language regarding the concomitant use of 
moderate CYP3A4 inhibitors. 
Rationale for change: To address feedback from the FDA. 
3. Section 5.2, Exclusion Criteria 
Description of change: Updated with a new exclusion criterion specific to pre-existing 
conditions. 
Rationale for change: To address feedback from the FDA. 
4. Section 6.5.1, Criteria and Procedures for Dose Interruptions and Adjustments of 
Study Drug (Table 7: Guidelines for Interruption and Restarting of Study Drug) 
Description of change: Table was updated to refine the language defining the criteria for 
interruption and discontinuation.  Additionally, criterion specific to RPE has been added. 
Rationale for change: To address feedback from the FDA. 
5. Section 8.3.6 Laboratory Assessments (Table 10: Required Laboratory Analytes) 
Description of change: Added Vitamin D to the list of blood chemistries. 
Rational for change: Vitamin D was inadvertently omitted from the original protocol. 
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. 


Signature Page for VV-CLIN-016176 v2.0
Signature Page for VV-CLIN-016176 v2.0
Approval
Approval
Approval
Approver
Approval
Approver

SAP_001.pdf: 
Oficial Title: A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety 
of Pemigatinib in Participants With Advanced Non–Small Cell Lung Cancer With an FGFR Alteration 
Who Progressed on Previous Therapy (FIGHT-210)
NCT Number: NCT05253807
Document Date: Statistical Analysis Plan Version 1: 20-Oct-2023


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Statistical Analysis Plan 
TITLE PAGE 
INCB 54828-210 
A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the 
Efficacy and Safety of Pemigatinib in Participants with Advanced Non–Small 
Cell Lung Cancer With an FGFR Alteration who Progressed on Previous 
Therapy (FIGHT-210) 
IND Number: 
158,139 
EudraCT Number: 
2021-004934-12 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
United States  
Protocol Version: 
Protocol Amendment 1 dated 08 DEC 2021 
CRF Approval Date: 
25 MAR 2022 
SAP Version: 
Original 
SAP Author: 
 
 Biostatistics 
Date of Plan: 
20 OCT 2023 
This study is being conducted in compliance with Good Clinical Practice, 
including the archiving of essential documents. 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
TABLE OF CONTENTS .................................................................................................................2 
LIST OF ABBREVIATIONS ..........................................................................................................6 
1. 
INTRODUCTION ........................................................................................................8 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS.................................9 
2.1. 
Protocol and Case Report Form Version ......................................................................9 
2.2. 
Study Objectives and Endpoints ...................................................................................9 
3. 
STUDY DESIGN .......................................................................................................11 
3.1. 
Randomization ............................................................................................................12 
3.2. 
Control of Type I Error ...............................................................................................12 
3.3. 
Sample Size Considerations .......................................................................................13 
3.4. 
Schedule of Assessments ............................................................................................13 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................14 
4.1. 
Scheduled Study Evaluations and Study Periods .......................................................14 
4.1.1. 
Day 1 ...........................................................................................................................14 
4.1.2. 
Study Day ...................................................................................................................14 
4.1.3. 
Baseline Value ............................................................................................................14 
4.1.4. 
Handling of Missing and Incomplete Dates ...............................................................14 
4.1.5. 
Cycle Length and Duration .........................................................................................15 
4.1.6. 
Analysis Window ........................................................................................................15 
4.2. 
Variable Definitions ....................................................................................................15 
4.2.1. 
Prior and Concomitant Medication .............................................................................15 
5. 
STATISTICAL METHODOLOGY ...........................................................................16 
5.1. 
General Methodology .................................................................................................16 
5.2. 
Treatment Groups .......................................................................................................16 
5.3. 
Analysis Populations ..................................................................................................16 
5.3.1. 
Full Analysis Set .........................................................................................................16 
5.3.2. 
Safety Population ........................................................................................................16 
6. 
BASELINE, EXPOSURE, AND DISPOSITION ......................................................17 
6.1. 
Demographics, Baseline Characteristics, and Disease History ..................................17 
6.1.1. 
Demographics and Baseline Characteristics ...............................................................17 


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6.1.2. 
Baseline Disease Characteristics ................................................................................17 
6.1.3. 
Disease History ...........................................................................................................17 
6.1.4. 
Prior Therapy ..............................................................................................................17 
6.1.5. 
Medical History ..........................................................................................................17 
6.2. 
Disposition of Participants ..........................................................................................17 
6.3. 
Exposure .....................................................................................................................18 
6.4. 
Study Drug Compliance .............................................................................................18 
6.5. 
Prior and Concomitant Medication .............................................................................18 
7. 
EFFICACY .................................................................................................................19 
7.1. 
Efficacy Hypothesis ....................................................................................................19 
7.2. 
Analysis of the Primary Efficacy Parameter ..............................................................19 
7.2.1. 
Primary Efficacy Analysis ..........................................................................................19 
7.2.1.1. 
Response Criteria ........................................................................................................19 
7.2.1.2. 
Objective Response Rates and Best Overall Response ..............................................19 
7.2.2. 
Subgroup Analyses for Primary Endpoint ..................................................................19 
7.3. 
Analysis of the Secondary Efficacy Parameter ..........................................................20 
7.3.1. 
Secondary Endpoints Involving Objective Response Rate ........................................20 
7.3.2. 
Progression-Free Survival ..........................................................................................20 
7.3.3. 
Duration of Response .................................................................................................21 
7.3.4. 
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 
7.5. 
Analysis of Exploratory Efficacy Variables ...............................................................22 
 
22 
7.5.2. 
Eastern Cooperative Oncology Group Performance Status ........................................23 
8. 
SAFETY AND TOLERABILITY ..............................................................................24 
8.1. 
General Considerations ...............................................................................................24 
8.2. 
Adverse Events ...........................................................................................................24 
8.2.1. 
Adverse Event Definitions ..........................................................................................24 
8.2.2. 
Adverse Event Listings ...............................................................................................25 
8.3. 
Clinical Laboratory Tests ...........................................................................................25 
8.3.1. 
Laboratory Value Definitions .....................................................................................25 
8.3.2. 
Laboratory Value Summaries .....................................................................................25 


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8.3.3. 
Potential Hy's Law Events ..........................................................................................25 
8.4. 
Vital Signs ..................................................................................................................25 
8.5. 
Electrocardiograms .....................................................................................................26 
9. 
INTERIM ANALYSIS ...............................................................................................26 
10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................27 
10.1. 
Changes to Protocol-Defined Analyses ......................................................................27 
10.2. 
Changes to the Statistical Analysis Plan .....................................................................27 
11. 
REFERENCES ...........................................................................................................28 
APPENDIX A. PLANNED TABLES, FIGURES, AND LISTINGS ........................................29 
 


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LIST OF TABLES 
Table 1: 
Objectives and Endpoints .............................................................................................9 
Table 2: 
Evaluation and Censoring of Progression-Free Survival ............................................20 
 
 
22 
Table 4: 
Criteria for Clinically Notable Vital Sign Abnormalities ...........................................26 
Table 5: 
Criteria for Clinically Notable Electrocardiogram Abnormalities .............................26 
Table 6: 
Statistical Analysis Plan Versions ..............................................................................27 
 
LIST OF FIGURES 
Figure 1: 
Study Design Scheme .................................................................................................12 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AE 
adverse event 
  
 
BOR 
best overall response 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
 
 
  
 
CR 
complete response  
CRF 
case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DOR 
duration of response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
 
 
 
 
 
EQ VAS 
EuroQoL visual analogue screening 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
FGFR 
fibroblast growth factor receptor 
FGFR1-3 
fibroblast growth factor receptor 1, 2, or 3 
ICR 
independent central radiology 
KM 
Kaplan-Meier 
NCI 
National Cancer Institute 
NE 
not evaluable 
NSCLC 
non–small cell lung cancer 
ORR 
objective response rate  
OS 
overall survival 
PD 
progressive disease 
PFS 
progression-free survival 
 
 
PP 
per Protocol 
PR 
partial response 
PT 
preferred term 


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Abbreviation 
Definition 
QoL 
quality of life 
QTc 
QT interval corrected 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAP 
Statistical Analysis Plan 
SD 
stable disease 
TEAE 
treatment-emergent adverse event 
 
 
TNM 
tumor nodes metastasis 
ULN 
upper limit of normal 
WHO 
World Health Organization 
 


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1. 
INTRODUCTION 
This is a Phase 2 open-label, single-arm, multicenter study of pemigatinib in participants with 
advanced NSCLC with an FGFR alteration who progressed on previous therapy. Section 2 of the 
Protocol provides a detailed description of the investigational product, target patient population, 
rationale for doses to be examined, and potential risks and benefits of treatment with 
pemigatinib. 
The purpose of this SAP is to provide details of the statistical analyses that have been outlined in 
the Study INCB 54828-210 Protocol. 


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2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 54828-210 Protocol Amendment 1 dated 08 DEC 2021 and CRFs 
approved 25 MAR 2022. Unless superseded by an amendment, this SAP will be effective for all 
subsequent Protocol amendments and eCRF versions. 
2.2. 
Study Objectives and Endpoints 
Table 1 presents the objectives and endpoints. 
Table 1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To determine the efficacy of pemigatinib in 
participants in Cohort A  
ORR in Cohort A, defined as the proportion of 
participants who achieve a CR or PR based on 
RECIST v1.1. Clinical response will be 
determined by an ICR review. 
Secondary 
To evaluate the efficacy of pemigatinib in 
participants in Cohort B 
ORR in Cohort B, defined as the proportion of 
participants who achieve a CR or PR based on 
RECIST v1.1. Clinical response will be 
determined by an ICR review. 
To evaluate the efficacy of pemigatinib in 
Cohort A 
• 
PFS in Cohort A, defined as the time from 
first dose of study drug until PD (according to 
RECIST v1.1 as assessed by an ICR review) 
or death, whichever is first. 
• 
DOR in Cohort A, defined as the time from 
the date of first CR or PR until the date of the 
first PD (according to RECIST v1.1 as 
assessed by an ICR review), or death, 
whichever is first. 
• 
OS in Cohort A, defined as the time from first 
dose of study drug to death of any cause. 
To assess safety and tolerability of pemigatinib in 
all participants 
Safety and tolerability, as assessed by the 
occurrence of TEAEs and treatment-related 
TEAEs according to NCI CTCAE v5.0, physical 
examination changes, vital sign changes, 
laboratory evaluations, and ECGs. 


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Table 1: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 
Exploratory 
To evaluate the efficacy of pemigatinib in 
Cohort B 
PFS in Cohort B, defined as the time from first 
dose of study drug until PD (according to 
RECIST v1.1 as assessed by an ICR review) or 
death, whichever is first. 
DOR in Cohort B, defined as the time from the 
date of first CR or PR until the date of the first PD 
(according to RECIST v1.1 as assessed by an ICR 
review), or death, whichever is first. 
OS in Cohort B, defined as the time from first 
dose of study drug to death of any cause. 
 


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3. 
STUDY DESIGN 
This is an open-label, monotherapy study of pemigatinib in participants with advanced NSCLC 
with an FGFR alteration who progressed while on previous therapy. The study includes 
2 cohorts, Cohort A and Cohort B, and will enroll approximately 125 participants. Participants 
will receive pemigatinib 13.5 mg once daily on an intermittent dose schedule (2 weeks on 
therapy and 1 week off therapy schedule). Full study drug administration information can be 
found in the Protocol, Section 6. 
All potential participants must have documented FGFR1-3 mutations or fusions/rearrangements 
before enrollment. Acceptable FGFR alterations may be classified as fusion, rearrangement, 
translocation, mutation, or fluorescent in-situ hybridization-positive. 
Previous therapies may include targeted therapies, chemotherapeutic agents and 
immunotherapies, with or without radiotherapy. Participants receiving radiotherapy to target 
lesion(s) must show progression of the target lesion prior to entry into the study. 
Due to the different histology (eg, squamous, nonsquamous, and large cell) and genetic markers 
(eg, epidermal growth factor receptor mutant), participants enrolled in this study will be assigned 
to 1 of 2 cohorts as follows: 
• Cohort A: Squamous NSCLC with known or likely FGFR1-3 driver mutations outside 
the kinase domain or fusions/rearrangements (n ≈ 100). 
• Cohort B: Nonsquamous NSCLC with known or likely FGFR1-3 driver mutations 
outside the kinase domain or fusions/rearrangements, including participants who have 
relapsed on prior targeted therapy (n ≈ 25). 
Treatment will start on Cycle 1 Day 1. Participants will undergo regular safety assessments 
during treatment, as well as regular efficacy assessments. Participants will be allowed to 
continue study drug 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 Scheme 
 
3.1. 
Randomization 
Not applicable. 
3.2. 
Control of Type I Error 
Unless otherwise specified, all CIs provided will be at the 95% confidence level. 


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3.3. 
Sample Size Considerations 
Approximately 125 participants with select FGFR alterations are planned for the final analysis of 
the primary endpoint of ORR. With the assumed rates of 40% for pemigatinib, a sample size of 
approximately 100 participants would provide about > 95% probability of having a 95% CI with 
a lower limit of > 20%. 
Up to 25 participants will be enrolled in Cohort B, which will provide > 80% chance of 
observing at least 3 responders in this cohort if the underlying ORR is 20%. 
3.4. 
Schedule of Assessments 
Refer to Protocol Amendment 1 dated 08 DEC 2021 for a full description of all study procedures 
and assessment schedules for this study. 


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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 pemigatinib is administered to the participants. 
4.1.2. 
Study Day 
If a visit/reporting date is on or after Day 1, 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 Day 1, 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 the last nonmissing measurement obtained before the first administration of 
pemigatinib. When scheduled assessments and unscheduled assessments occur on the same day 
and the 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 assessment 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 Dates 
In general, values for missing dates will not be handled unless methods for handling missing 
dates are specified in this section or relevant sections. The original reported dates collected on 
the eCRF should be used in all relevant listings. The following rules will be used for handling 
partial dates for analyses requiring dates. 
When calculating time since diagnosis of cancer, partial cancer diagnosis date will be handled as 
follows in the calculation: 
• If only the day is missing, then the first day of the month will be used. 
• If both the month and day are missing, then 01 JAN of the year will be used. 
• If the diagnosis date is completely missing, then the time since diagnosis will not be 
calculated. 


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When date of last dose is used in deriving variables, such as duration of treatment or TEAE flag, 
a missing or partial date of the last dose will be handled as follows: 
• If only the day is missing, then use the earlier date of the last day of the month or the 
date that the participant discontinued treatment will be used. 
• Otherwise, the date that the participant discontinued treatment will be used as the date 
of the last dose. 
For relevant efficacy endpoints, a partial date of the death date will be handled as follows in the 
calculation: 
• If mmyyyy for the last known alive date = mmyyyy for the death date, then the death 
date will be set to the day after the last known alive date. 
• If mmyyyy for the last known alive 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 pemigatinib is administered. The scheduled cycle 
length is 21 days. The actual Day 1 of subsequent cycles will correspond with the first day of 
administration of pemigatinib 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 
4.2.1. 
Prior and Concomitant Medication 
Prior medication is defined as any nonstudy medication started before the first dose of 
pemigatinib. 
Concomitant medication is defined as any nonstudy medication that is started accordingly: 
• Before the date of first administration of pemigatinib 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 pemigatinib and is ongoing or ends during 
the course of study drug administration. 


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A prior medication could also be classified as "both prior and concomitant medication," if the 
end date is on or after the first dose of pemigatinib. In the listing, it will be indicated whether a 
medication is only prior, only concomitant, or both prior and concomitant. 
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 or later) will be used 
for the generation of all tables, listings, and statistical analyses. 
Interim analyses will not be conducted due to early termination. 
5.2. 
Treatment Groups 
This is an open-label, single treatment group study. Participants will be listed by treatment 
cohort. Cohort determination will be based on the results of histology and genetic markers from 
central genomics laboratory. 
5.3. 
Analysis Populations 
5.3.1. 
Full Analysis Set 
The FAS will include all enrolled participants who received at least 1 dose of pemigatinib. 
Participants will be analyzed according to the treatment cohort to which they are initially 
assigned. The FAS will be used for the listings of demographics, baseline characteristics, 
participant disposition, and analyses of all efficacy data. 
5.3.2. 
Safety Population 
The safety population will include all enrolled participants who received at least 1 dose of 
pemigatinib. All safety analyses will be conducted using the safety population. 


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6. 
BASELINE, EXPOSURE, AND DISPOSITION 
Appendix A provides a list of data displays. 
6.1. 
Demographics, Baseline Characteristics, and Disease History 
6.1.1. 
Demographics and Baseline Characteristics 
The following demographics and baseline characteristics will be listed for the FAS: age, sex, 
race, ethnicity, weight and height. 
6.1.2. 
Baseline Disease Characteristics 
The following baseline disease characteristics will be listed for the FAS: ECOG performance 
status and baseline phosphate. 
6.1.3. 
Disease History 
The time since diagnosis, tumor histology, TNM staging at initial diagnosis, current TNM 
staging, current stage of disease, current sites of disease, smoking status, and tumor marker test 
results will be listed for all participants in the FAS. 
Time since diagnosis will be calculated as follows: 
Time since diagnosis (years) = (Day 1 date – date of diagnosis + 1) / 365.25 
6.1.4. 
Prior Therapy 
The prior systemic cancer therapy regimens will be listed for all participants in the FAS. The 
component drugs of prior systemic therapy regimens will be coded using the WHO Drug 
Dictionary. The prior systemic cancer therapy 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 for all participants in the FAS. 
The prior radiotherapy type, body site, start and stop dates, total dose, and best response will be 
listed for all participants in the FAS. 
The date and description of the prior surgery/procedure for disease under study will be listed for 
all participants in the FAS. 
6.1.5. 
Medical History 
For participants in the FAS, medical history will be listed. This list will include the medical 
history event for each body system/organ class as documented on the eCRF. 
6.2. 
Disposition of Participants 
The treatment group, that is, if the treatment is ongoing or discontinued, and the primary reason 
for treatment discontinuation, or if the participant is still in study or withdrawal, and the primary 
reason for study withdrawal, will be listed for all participants in the FAS. 


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6.3. 
Exposure 
For participants in the safety population, exposure to pemigatinib will be listed as the following: 
• Number of treatment cycles:  
Number of cycles with a nonzero dose of pemigatinib. 
• Duration of treatment with pemigatinib (days):  
Date of last dose of pemigatinib – date of first dose of pemigatinib + 1 
• Average daily dose of pemigatinib (mg/day):  
Total actual dose taken (mg) / duration of treatment with pemigatinib (days) 
Total actual dose taken will be calculated based on the information entered on the 
Drug Accountability eCRF. 
• Pemigatinib dose modifications:  
Participants who had pemigatinib dose reduction and interruption. 
6.4. 
Study Drug Compliance 
For participants in the safety population, overall compliance (%) for pemigatinib will be 
calculated for all participants 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 are dispensed drugs that have not been returned yet, the actual 
dose taken starting from the dispense date of the unreturned drugs will be imputed by the dose 
taken as reported on the Dosing eCRF. 
6.5. 
Prior and Concomitant Medication 
Prior medications and concomitant medications will be coded using the WHO Drug Dictionary. 
The prior and concomitant medication will be listed for participants in the FAS by WHO drug 
class and WHO drug preferred term. In the data listing, each medication will be recorded as only 
prior, only concomitant, or both prior and concomitant. 


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7. 
EFFICACY 
Appendix A provides a list of data displays. 
7.1. 
Efficacy Hypothesis 
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 Cohort A. Objective response rate is defined as the 
proportion of participants who achieve a CR or PR based on RECIST v1.1 (Eisenhauer 2009), as 
assessed by an ICR review committee. Confirmation of CR and PR is required and documented 
in the ICR charter. This analysis will be based on the FAS. Participants 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. 
7.2.1.1. 
Response Criteria 
Overall disease status will be categorized and listed using RECIST v1.1 (Eisenhauer 2009). 
Participants will have their overall response evaluated as CR, PR, SD, PD, or NE at each 
postbaseline radiologic assessment based on changes in target lesions, nontarget lesions, and 
appearance of new lesions. 
7.2.1.2. 
Objective Response Rates and Best Overall Response 
A participant is considered an objective responder if they have a best overall response of CR or 
PR at any postbaseline visit prior to first PD. 
In general, under the RECIST v1.1, BOR is the best response recorded postbaseline prior to and 
including the first PD, in the order of CR, PR, SD, PD, and NE. The BOR will be determined 
from response assessments before or on the same day as the new anticancer therapy. If any 
alternative cancer therapy is taken while on study, any subsequent assessment(s) will be 
excluded from the BOR determination. A BOR of CR or PR needs to be confirmed; the 
confirmation method is described in the ICR charter. 
In the case of SD, measurements must meet the SD criteria at least once after the date of first 
dose (ie, a minimum interval of 42 days). Participants who fail to meet this criterion will have 
either a BOR of PD, if the next available assessment indicates PD, or NE, if there is no 
additional assessment available. 
7.2.2. 
Subgroup Analyses for Primary Endpoint 
Not applicable. 


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7.3. 
Analysis of the Secondary Efficacy Parameter 
7.3.1. 
Secondary Endpoints Involving Objective Response Rate 
The ORR in Cohort B is defined as the proportion of participants who achieve a CR or a PR 
based RECIST v1.1 as assessed by an ICR review. Confirmation of CR and PR is required and 
documented in the ICR charter. This analysis will be based on the FAS. Participants 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. 
7.3.2. 
Progression-Free Survival 
Progression-free survival is defined as the time from the date of first dose of pemigatinib (Day 1) 
to the date of the first documented PD or death due to any cause, whichever is first. Progressive 
disease will be evaluated according to RECIST v1.1 and assessed by an ICR review. Partial 
death dates will be handled using the rules described in Section 4.1.4. Participants who are alive 
without progression, before the analysis cutoff date, will be censored. Censoring for PFS will 
follow the algorithm outlined in Table 2 based on FDA guidance (FDA 2015, FDA 2018). 
Table 2: 
Evaluation and Censoring of Progression-Free Survival 
Situation 
Outcome 
Date of Progression or Censoring 
No baseline tumor assessments 
Censored 
Day 1 
No valid postbaseline response assessments 
Censored 
Day 1 
Progression documented between scheduled 
response assessments 
Progressed 
Date of first overall response of PD 
No progression 
Censored 
Date of last valid radiologic assessment 
(not NE and not missing) 
Study discontinuation for undocumented 
progression 
Censored 
Date of last valid radiologic assessment 
(not NE and not missing) 
Study discontinuation for toxicity or other reason 
Censored 
Date of last valid radiologic assessment 
(not NE and not missing) 
New anticancer treatment started 
Censored 
Date of last valid radiologic assessment 
(not NE and not missing) on/before starting a 
new anticancer treatment 
Death before first PD assessment 
Progressed 
Date of death 
Death between adequate response assessments 
Progressed 
Date of death 
Death or progression after 2 or more missed 
assessments 
Censored 
Date of last valid radiologic assessment 
(not NE and not missing) 
 


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Progression-free survival data will be analyzed by the KM method in Cohort A. The number of 
participants who progressed or died and the number of participants censored will be summarized. 
The KM estimates of median PFS will be presented with its 95% CI. The 95% CI will be 
calculated using the generalization of Brookmeyer and Crowley's method (1982) with log-log 
transformation (Klein and Moeschberger 1997). 
7.3.3. 
Duration of Response 
For objective responders, DOR is defined as the time from the date that a participant first 
achieves CR or PR, until the date of first documented disease progression or death, whichever is 
first. Responses and PD will be evaluated based on RECIST v1.1 by an ICR review. The partial 
death dates will be handled using the rules described in Section 4.1.4. Participants who are alive 
without progression before the analysis cutoff date will be censored. Censoring of DOR will 
follow the same algorithm as the censoring of PFS (see Section 7.3.2). 
The DOR data will be analyzed by the KM method in Cohort A. The total number of responders, 
the number of participants who progressed or died, and the participants censored will be 
summarized. The KM estimate of median DOR will be presented with its 95% CI. The 95% CI 
will be calculated using the generalization of Brookmeyer and Crowley's method (1982) with 
log-log transformation (Klein and Moeschberger 1997). 
7.3.4. 
Overall Survival 
Overall survival is defined as the time from the date of first dose of pemigatinib to the date of 
death due to any cause. Date of death will be determined using Death Report, Survival 
Follow-up, and Participant Status eCRFs. Participants who are lost to follow-up or still alive at 
the time of the analysis will be right-censored at the earlier of the date the participant was last 
known alive and clinical data cutoff date for the analysis. The last known alive date is defined as 
the later of the last study visit and the date the participant was last known alive from the Survival 
Follow-up and Participant Status eCRFs. The partial death dates will be handled using the rules 
described in Section 4.1.4. 
The OS will be analyzed by the KM method in Cohort A. The number of participants who died 
and the number of participants censored will be summarized. The median survival will be 
estimated using the KM method. The 95% CIs for median survival time will be calculated using 
the generalization of Brookmeyer and Crowley's method (1982) with log-log transformation 
(Klein and Moeschberger 1997). 
7.4. 
Analysis of Other Efficacy Parameters 
7.4.1. 
Largest Percentage Reduction in Sum of Diameters of Target Lesions 
For each participant in the FAS with measurable target lesions at baseline, target lesion sizes will 
be measured by sum of diameters. The best percentage change from baseline, defined as the 
largest decrease in target lesion size for each participant during the study, will be listed. 


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Per RECIST criteria, 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 a target lesion is 
unaccounted for in a particular postbaseline timepoint (ie, assessment missing or not evaluable), 
then the overall sum of diameters for target lesions will not be evaluable for that postbaseline 
timepoint. 
7.5. 
Analysis of Exploratory Efficacy Variables 
The PFS, DOR (ie, per RECIST v1.1 and as assessed by ICR), and OS in Cohort B will be 
analyzed for the FAS in the same fashion as Cohort A. 


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7.5.2. 
Eastern Cooperative Oncology Group Performance Status 
The ECOG performance status at scheduled assessment times will be listed by treatment cohorts. 


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8. 
SAFETY AND TOLERABILITY 
Appendix A provides a list of data displays. 
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 PTs reported on relatively few participants. 
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 the 
first dose of study treatment until 30 days of the last dose of study treatment. Analysis of AEs (as 
discussed below) will be limited to TEAEs, but data listings will include all AEs regardless of 
their timing and in relation to study treatment administration. For purposes of analysis, all AEs 
will be considered TEAEs unless the AE can unequivocally be defined as not 
treatment-emergent. 
Adverse events will be listed by Medical Dictionary for Regulatory Activities PT and system 
organ class. Severity of AEs will be graded using the NCI CTCAE v5.0. The CTCAE 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 v5.0 criteria, it will be rated on a scale of 1 to 5 as follows: 1 = mild, 2 = moderate, 
3 = severe, 4 = life-threatening, and 5 = fatal. 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. If the investigator does not specify the relationship of the AE to study 
drug, the AE will be considered to be treatment-related. The incidence of AEs and 
treatment-related AEs will be listed. In addition, serious TEAEs and serious AEs will be listed. 
Any missing data pertaining to date of onset, causality, or severity of an AE must be queried for 
resolution. Unresolved missing causality or severity of an AE will be handled according to the 
following rules: 
• An unresolved missing causality will be considered treatment-related. 
• An unresolved missing severity will be identified as an unknown severity. 


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8.2.2. 
Adverse Event Listings 
The following listings will be produced: 
• Listing of AEs 
• Listing of serious AEs 
• Listing of Grade 3 or higher AEs 
• Listing of AEs with a fatal outcome 
• Listing of pemigatinib treatment-related AEs 
• Listing of AEs leading to interruption, reduction, or discontinuation of pemigatinib 
8.3. 
Clinical Laboratory Tests 
8.3.1. 
Laboratory Value Definitions 
Laboratory values and change from baseline values will be listed. Baseline will be determined 
according to Section 4.1.3. If there are multiple values that meet the criteria for baseline, 
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 upon the 
numerical component of CTCAE v5.0. 
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. 
Severity grades will be assigned to laboratory test values based on the numerical component of 
CTCAE v5.0. CTCAE grades will be reported. Separate lists for abnormally high and 
abnormally low laboratory values will be provided when the laboratory parameter has both high 
and low grading criteria. 
8.3.3. 
Potential Hy's Law Events 
The participants with elevated alanine transaminase or aspartate transaminase > 3 × ULN range 
and alkaline phosphatase < 2 × ULN range accompanied by total bilirubin > 2 × ULN range at 
the same visit will be listed by cohort. 
8.4. 
Vital Signs 
Values at each scheduled visit for vital signs, including weight, systolic blood pressure, diastolic 
blood pressure, pulse, temperature, and respiratory rate, will be listed. 


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Criteria for clinically notable vital sign abnormalities are defined in Table 4. The abnormal 
values for participants exhibiting clinically notable vital sign abnormalities will be listed along 
with their cohort. Alert vital signs are defined as an absolute value outside the defined normal 
range and percentage change from baseline greater than 25%. Note that the definition of alert 
vital signs does not apply for body temperature and weight. The abnormal values for participants 
exhibiting alert vital sign abnormalities will be listed. 
Table 4: 
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 breaths/min 
< 8 breaths/min 
8.5. 
Electrocardiograms 
Twelve-lead ECGs including heart rate (HR), PR, QRS, QT and QTc intervals will be obtained 
for each participant during the study. Values at each scheduled visit, change, and percent change 
from baseline will be listed for each ECG parameter. Baseline will be determined as the average 
of all nonmissing values before the first administration of pemigatinib. 
Criteria for clinically notable ECG abnormalities are defined in Table 5. The ECG values will 
also be considered abnormal if the absolute percentage change from baseline is more than 25% 
(QRS 30%). Participants exhibiting ECG abnormalities will be listed with study visit and 
assigned cohort. Abnormal values for participants with alert ECG values, defined as both the 
absolute value and the percentage change from baseline being outside the defined normal ranges, 
will be identified and listed. 
Table 5: 
Criteria for Clinically Notable Electrocardiogram Abnormalities 
Parameter  
High Threshold 
Low Threshold 
PR  
> 220 ms 
< 75 ms 
HR  
> 100 bpm 
< 45 bpm 
QT  
> 500 ms 
< 300 ms 
QRS  
> 120 ms 
< 50 ms 
QTc 
> 460 ms 
< 295 ms 
9. 
INTERIM ANALYSIS 
Not applicable. 


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10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN 
All versions of the SAP are listed in Table 6. 
Table 6: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
20 OCT 2023 
10.1. 
Changes to Protocol-Defined Analyses 
A decision was made to terminate study enrollment. At the time of study termination there were 
fewer than 10 participants enrolled; as a result, an interim futility analysis and a sensitivity 
analysis will not be conducted. The RECIST-evaluable population and the Per-Protocol 
population will not be generated for analysis. 
10.2. 
Changes to the Statistical Analysis Plan 
Not applicable. 


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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 (v1.1). Eur J Cancer 2009;45:228-247. 
Food and Drug Administration. Guidance for industry: clinical trial endpoints for the approval of 
non–small cell lung cancer drugs and biologics. 2015. 
Food and Drug Administration. Guidance for industry: clinical trial endpoints for the approval of 
cancer drugs and biologics. 2018. 
Klein JP, Moeschberger ML. Survival analysis: techniques for censored and truncated data. New 
York: Springer-Verlag. 1997. 


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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. Shells are provided in a separate document for tables that are not in the Standard Safety 
Tables v1.13. 
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. 
Tables 
Table No. 
Title 
Population 
Standard 
Efficacy 
2.1 Primary Efficacy 
2.1.1 
Summary of Best Overall Response and Objective Response Rate – 
Cohort A 
FAS 
 
2.2 Secondary Efficacy 
2.2.1 
Summary of Best Overall Response and Objective Response Rate – 
Cohort B 
FAS 
 
2.2.2 
Summary of Progression-Free Survival – Cohort A 
FAS 
 
2.2.3 
Summary of Duration of Response – Cohort A 
FAS 
 
2.2.4 
Summary of Overall Survival – Cohort A 
FAS 
 
Listings 
Listing No. 
Title 
2.1 Participant Disposition 
2.1.1 
Participant Enrollment and Disposition Status 
2.1.2 
Participant Inclusion and Exclusion Criteria Violations 
2.3 Safety Analyses 
2.3.1 
Analysis Populations 
2.4 Demographics and Baseline Characteristics (Including Concomitant Medications) 
2.4.1 
Demographic and Baseline Characteristics 
2.4.2 
Disease History 
2.4.3 
Prior Radiation Treatment  
2.4.4 
Prior Systemic Therapy 
2.4.5 
Prior Surgery or Surgical Procedure 
2.4.6 
Medical History 
2.4.7 
Prior and Concomitant Medication 
2.4.8 
Procedures and Nondrug Therapy 
2.4.9 
Post Therapy 
2.5 Drug Compliance 
2.5.1 
Study Drug Compliance 
2.5.2 
Study Drug Administration 
2.6 Efficacy 
2.6.1 
Deaths 
2.6.2 
Best Overall Response, Duration of Response, Progression-Free Survival, and Overall Survival 
2.6.3 
Overall Response Assessment by Visit – RECIST 
2.6.4 
Response Assessment: Target Lesions – RECIST 
2.6.5 
Response Assessment: Nontarget Lesions – RECIST 
2.6.6 
Response Assessment: New Lesions – RECIST 
2.6.7 
FGFR Status 


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Listing No. 
Title 
2.6.8 
ECOG Status 
 
 
 
 
2.7 Adverse Events 
2.7.1 
Adverse Events  
2.7.2 
Serious Adverse Events 
2.7.3 
Grade 3 and higher Adverse Events 
2.7.4 
Fatal Adverse Events 
2.7.5 
Treatment-Related Adverse Events 
2.7.6 
Adverse Events Leading to Interruption, Reduction, or Discontinuation of Pemigatinib 
2.8 Laboratory Data 
2.8.1 
Clinical Laboratory Values – Hematology 
2.8.2 
Clinical Laboratory Values – Chemistry 
2.8.3 
Clinical Laboratory Values – Coagulation 
2.8.4 
Clinical Laboratory Values – Urinalysis 
2.8.5 
Abnormal Clinical Laboratory Values – Hematology 
2.8.6 
Abnormal Clinical Laboratory Values – Chemistry 
2.8.7 
Abnormal Clinical Laboratory Values – Coagulation 
2.8.8 
Potential Hy's Law Events  
2.8.9 
Serology Laboratory Test 
2.8.10 
Pregnancy Test 
2.9 Vital Signs 
2.9.1 
Vital Signs 
2.9.2 
Abnormal Vital Sign Values 
2.9.3 
Alert Vital Sign Values 
2.10 ECG 
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 Eye Examinations 
2.11.1 
Eye Examination 
2.11.2 
Optical Coherence Tomography