A Phase 2 Study of Erdafitinib in Subjects With Advanced Solid Tumors and FGFR Gene Alterations
Phase: PHASE2
Conditions: Advanced Solid Tumor
Sponsor: Janssen Research & Development, LLC

CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved, Date: 22 February 2023
Janssen Research & Development *
Clinical Protocol
A Phase 2 Study of Erdafitinib in Subjects with Advanced Solid Tumors and FGFR Gene
Alterations
Protocol 42756493CAN2002; Phase 2
Amendment 6
JNJ-42756493 (erdafitinib)
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries/territories. Therefore, the legal entity acting as the sponsor for Janssen Research &
Development studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP;
Janssen Biologics, BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Pharmaceutica NV; Janssen
Sciences Ireland UC; Janssen Biopharma Inc.; or Janssen Research & Development, LLC. The term
“sponsor” is used throughout the protocol to represent these various legal entities; the sponsor is identified
on the Contact Information page that accompanies the protocol.
United States (US) sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).
IND: 143545
EudraCT NUMBER:    2019-002113-19
Status: 
Approved
Date: 
22 February 2023
Prepared by: Janssen Research & Development, LLC
EDMS number: 
EDMS-ERI-179740920, 9.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory
requirements.
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that
the Company customarily holds close and treats as confidential. The information is being provided under
the assurance that the recipient will maintain the confidentiality of the information under applicable
statutes, regulations, rules, protective orders or otherwise.
NCT04083976

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
2
Status: Approved, Date: 22 February 2023
TABLE OF CONTENTS
TABLE OF CONTENTS............................................................................................................................... 2
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 6
PROTOCOL AMENDMENTS....................................................................................................................... 7
1. 
PROTOCOL SUMMARY..................................................................................................................... 9
1.1. 
Synopsis........................................................................................................................................... 9
1.2. 
Schema.......................................................................................................................................... 12
1.3. 
Schedule of Activities: For Adults (≥18 Years of Age)................................................................... 13
1.4. 
Schedule of Activities: For Children and Adolescents (≥6 to <18 Years of Age)........................... 18
2. 
INTRODUCTION................................................................................................................................ 25
2.1. 
Study Rationale.............................................................................................................................. 25
2.2. 
Background .................................................................................................................................... 26
2.2.1. 
Erdafitinib.................................................................................................................................... 26
2.2.2. 
The Role of Fibroblast Growth Factor Receptor......................................................................... 27
2.2.3. 
Fibroblast Growth Factor Receptor Alterations in Solid Tumors ................................................ 28
2.3. 
Benefit-Risk Assessment............................................................................................................... 32
3. 
OBJECTIVES AND ENDPOINTS..................................................................................................... 33
3.1. 
Cholangiocarcinoma Expansion Cohort......................................................................................... 34
4. 
STUDY DESIGN ................................................................................................................................ 34
4.1. 
Overall Design................................................................................................................................ 34
4.2. 
Scientific Rationale for Study Design............................................................................................. 38
4.2.1. 
Cohort Design............................................................................................................................. 38
4.2.2. 
Biomarker Collection................................................................................................................... 39
4.2.3. 
Patient-reported Outcomes Research........................................................................................ 40
4.2.4. 
Study-Specific Ethical Design Considerations ........................................................................... 40
4.2.5. 
Participant Input Into Design ...................................................................................................... 41
4.3. 
Justification for Dose...................................................................................................................... 42
5. 
STUDY POPULATION ...................................................................................................................... 46
5.1. 
Inclusion Criteria............................................................................................................................ 46
5.2. 
Exclusion Criteria........................................................................................................................... 50
5.3. 
Lifestyle Considerations................................................................................................................. 53
5.4. 
Screen Failures.............................................................................................................................. 53
5.5. 
Study Completion (ie, End of Data Collection Timepoint) and End of Study................................. 54
5.5.1. 
Study Completion (ie, End of Data Collection Timepoint) Definition .......................................... 54
5.5.2. 
End of Study Definition –Overall Study ..................................................................................... 54
6. 
STUDY DRUG ................................................................................................................................... 54
6.1. 
Study Drug Administered ............................................................................................................... 54
6.2. 
Preparation/Handling/Storage/ Accountability ............................................................................... 57
6.3. 
Measures to Minimize Bias: Randomization and Blinding............................................................. 58
6.4. 
Study Drug Compliance ................................................................................................................. 58
6.5. 
Concomitant Therapies.................................................................................................................. 58
6.5.1. 
Permitted Medications ................................................................................................................ 58
6.5.2. 
Prohibited Medications ............................................................................................................... 59
6.5.3. 
Precautions for Concomitant Medications.................................................................................. 59
6.6. 
Dose Modifications......................................................................................................................... 60
6.6.1. 
Guidance for Specific Erdafitinib Toxicities ................................................................................ 63
6.6.1.1. 
Guidelines for the Management of Elevated Phosphate Levels ............................................. 63
6.6.1.2. 
Guidelines for the Management of Dry Mouth and Mucositis ................................................. 65

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
3
Status: Approved, Date: 22 February 2023
6.6.1.3. 
Guidelines for the Management of Dry Skin and Skin Toxicity............................................... 67
6.6.1.4. 
Guidelines for the Management of Nail Toxicity (Onycholysis, Onychodystrophy, and
Paronychia).............................................................................................................................. 68
6.6.1.5. 
Guidelines for the Management of Eye Toxicity Associated With Vision Changes ................ 70
6.6.1.6. 
Guidelines for the Management of Dry Eye ............................................................................ 72
6.7. 
Study Drug After Study Completion............................................................................................... 73
7. 
DISCONTINUATION OF STUDY DRUG AND SUBJECT
DISCONTINUATION/WITHDRAWAL............................................................................................... 73
7.1. 
Discontinuation of Study Drug ....................................................................................................... 73
7.2. 
Subject Discontinuation/Withdrawal From the Study..................................................................... 74
7.2.1. 
Withdrawal From the Use of Research Samples ....................................................................... 74
8. 
STUDY ASSESSMENTS AND PROCEDURES............................................................................... 74
8.1. 
Study Procedures........................................................................................................................... 75
8.1.1. 
Screening Phase ........................................................................................................................ 75
8.1.1.1. 
Molecular Eligibility Screening Period ..................................................................................... 75
8.1.1.2. 
Full-study Screening Period .................................................................................................... 77
8.1.2. 
Treatment Phase ........................................................................................................................ 77
8.1.3. 
End-of-Treatment Visit................................................................................................................ 77
8.1.4. 
Follow-Up Phase ........................................................................................................................ 78
8.2. 
Efficacy Assessments .................................................................................................................... 78
8.2.1. 
Evaluations ................................................................................................................................. 79
8.2.1.1. 
RECIST and RANO Assessment of Disease .......................................................................... 79
8.2.1.2. 
Radiographic Assessment....................................................................................................... 79
8.2.2. 
Continuation of Treatment After Disease Progression ............................................................... 79
8.3. 
Safety Assessments....................................................................................................................... 80
8.3.1. 
History and Physical Examinations ............................................................................................ 80
8.3.1.1. 
History and Physical Examinations for Children and Adolescent Subjects............................. 80
8.3.2. 
Vital Signs................................................................................................................................... 81
8.3.3. 
Electrocardiograms..................................................................................................................... 82
8.3.4. 
Clinical Safety Laboratory Assessments .................................................................................... 82
8.3.5. 
Ophthalmologic Examination...................................................................................................... 82
8.3.6. 
Performance Status.................................................................................................................... 83
8.3.7. 
Bone-related Assessments (Children and Adolescents)............................................................ 83
8.4. 
Adverse Events and Serious Adverse Events ............................................................................... 84
8.4.1. 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event
Information.................................................................................................................................. 84
8.4.2. 
Method of Detecting Adverse Events and Serious Adverse Events .......................................... 85
8.4.3. 
Follow-up of Adverse Events and Serious Adverse Events ....................................................... 85
8.4.4. 
Regulatory Reporting Requirements for Serious Adverse Events ............................................. 85
8.4.5. 
Pregnancy................................................................................................................................... 85
8.4.6. 
Disease-related Events and Disease-related Outcomes Not Qualifying as Adverse
Events or Serious Adverse Events............................................................................................. 85
8.4.7. 
Adverse Events of Special Interest............................................................................................. 86
8.5. 
Pharmacokinetics........................................................................................................................... 86
8.5.1. 
Analytical Procedures................................................................................................................. 87
8.6. 
Biomarkers..................................................................................................................................... 87
8.7. 
Tumor Markers............................................................................................................................... 88
8.8. 
Patient-reported Outcomes............................................................................................................ 88
8.9. 
Medical Resource Utilization.......................................................................................................... 89
9. 
STATISTICAL CONSIDERATIONS.................................................................................................. 89
9.1. 
Statistical Hypothesis..................................................................................................................... 90
9.2. 
Sample Size Determination ........................................................................................................... 90
9.2.1. 
Broad Panel Cohort.................................................................................................................... 90
9.2.2. 
Cholangiocarcinoma Expansion Cohort..................................................................................... 90
9.2.3. 
Pediatric Cohort.......................................................................................................................... 91

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
4
Status: Approved, Date: 22 February 2023
9.3. 
Populations for Analyses................................................................................................................ 91
9.3.1. 
Broad Panel Cohort.................................................................................................................... 91
9.3.2. 
Exploratory Cohort...................................................................................................................... 92
9.3.3. 
Cholangiocarcinoma Expansion Cohort..................................................................................... 92
9.3.4. 
Pediatric Cohort.......................................................................................................................... 92
9.4. 
Statistical Analyses ........................................................................................................................ 92
9.4.1. 
Primary Endpoint ........................................................................................................................ 92
9.4.2. 
Secondary Efficacy Endpoints.................................................................................................... 93
9.4.3. 
Efficacy Analyses........................................................................................................................ 93
9.4.3.1. 
Primary Analysis...................................................................................................................... 93
9.4.3.2. 
Final Analysis........................................................................................................................... 94
9.4.4. 
Pharmacokinetic and Pharmacodynamic Analyses ................................................................... 94
9.4.5. 
Biomarker Analyses.................................................................................................................... 95
9.4.6. 
Medical Resource Utilization and Patient-reported Outcomes Analyses................................... 95
9.4.7. 
Safety Analyses.......................................................................................................................... 96
9.5. 
Interim Analyses............................................................................................................................. 97
9.6. 
Data Review Committee ................................................................................................................ 99
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS.......................... 100
10.1. 
Appendix 1: Abbreviations ........................................................................................................... 100
10.2. 
Appendix 2: Clinical Laboratory Tests ......................................................................................... 102
10.3. 
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations....................................... 103
10.3.1. 
Regulatory and Ethical Considerations .................................................................................... 103
10.3.2. 
Financial Disclosure.................................................................................................................. 106
10.3.3. 
Informed Consent Process and Assent Form .......................................................................... 107
10.3.4. 
Data Protection ......................................................................................................................... 108
10.3.5. 
Long-Term Retention of Samples for Additional Future Research .......................................... 109
10.3.6. 
Committee Structure................................................................................................................. 109
10.3.7. 
Publication Policy/Dissemination of Clinical Study Data.......................................................... 109
10.3.8. 
Data Quality Assurance............................................................................................................ 111
10.3.9. 
Case Report Form Completion................................................................................................. 111
10.3.10. Source Documents ................................................................................................................... 112
10.3.11. Monitoring ................................................................................................................................. 112
10.3.12. On-site Audits ........................................................................................................................... 113
10.3.13. Record Retention...................................................................................................................... 113
10.3.14. Study and Site Start and Closure ............................................................................................. 114
10.4. 
Appendix 4: Adverse Events: Definitions and Procedures for Recording, Evaluating,
Follow-up, and Reporting............................................................................................................. 115
10.4.1. 
Adverse Event Definitions and Classifications ......................................................................... 115
10.4.2. 
Severity Criteria........................................................................................................................ 116
10.4.3. 
Special Reporting Situations .................................................................................................... 117
10.4.4. 
Procedures ............................................................................................................................... 118
10.4.5. 
Contacting Sponsor Regarding Safety..................................................................................... 120
10.4.6. 
Product Quality Complaint Handling......................................................................................... 120
10.5. 
Appendix 5: ECOG Performance Status Scale ........................................................................... 121
10.6. 
Appendix 6: ECOG/Karnofsky/Lansky Performance Scales ....................................................... 122
10.7. 
Appendix 7: Cockcroft-Gault (Adults) and CKiD Schwartz (Children [≥6 to <12 years] and
Adolescents [≥12 to <18 years]) Formulas for Estimated Creatinine Clearance......................... 123
10.8. 
Appendix 8: The Stages of Heart Failure –New York Heart Association (NYHA)
Classification ................................................................................................................................ 124
10.9. 
Appendix 9: Amsler Grid .............................................................................................................. 125
10.10. Appendix 10: Drugs Classified as Strong or Moderate In Vivo Inhibitors and Inducers of
CYP3A4/2C9 Enzymes................................................................................................................ 126
10.11. Appendix 11: List of Target Fibroblast Growth Factor Receptor (FGFR) Mutations.................... 127
10.12. Appendix 12: Guidance on Study Conduct During a National Disaster for Enrolled
Subjects ....................................................................................................................................... 128
10.13. Appendix 13: Long-term Extension Phase................................................................................... 130

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
5
Status: Approved, Date: 22 February 2023
10.14. Appendix 14: Protocol Amendment History................................................................................. 132
11. REFERENCES................................................................................................................................. 152
INVESTIGATOR AGREEMENT............................................................................................................... 155

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
6
Status: Approved, Date: 22 February 2023
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Frequency of FGFR Mutations and Fusions in Advanced Cancer........................................... 29
Table 2: 
FGFR Mutations and Fusions Observed in Common Pediatric Tumors .................................. 30
Table 3: 
Erdafitinib Dose Modification Rules Based on Erdafitinib-related Toxicity Severity................. 60
Table 4: 
Erdafitinib Dose Reduction Levels: Adults and Adolescents Aged ≥15 to <18 Years.............. 61
Table 5: 
Erdafitinib Dose Reduction Levels: Adolescents Aged ≥12 to <15 Years................................ 62
Table 6: 
Erdafitinib Dose Reduction Levels: Children Aged ≥6 to <12 Years ........................................ 63
Table 7: 
Grading of Hyperphosphatemia Adverse Events ..................................................................... 63
Table 8: 
Guidelines for Management of Serum Phosphate Elevation.................................................... 64
Table 9: 
Guidelines for Management of Dry Mouth (Xerostomia).......................................................... 66
Table 10:  Guidelines for the Management of Oral Mucositis..................................................................... 66
Table 11: Guidelines for Management of Dry Skin................................................................................... 68
Table 12: Grading of Nail Adverse Events................................................................................................ 68
Table 13: Guidelines for Management of Nail Toxicity (Onycholysis/ Onychodystrophy)........................ 69
Table 14: Guidelines for Management of Paronychia.............................................................................. 70
Table 15: Guidelines for Management of Eye Toxicity............................................................................. 71
Table 16: List of Tumor Histologies for Futility and Cap........................................................................... 98
Table 17: Schedule of Activities (Long-term Extension Phase).............................................................. 131
FIGURES
Figure 1: Schematic Overview of the Study............................................................................................. 12
Figure 2: Overlap of Pediatric Alterations with Broad Panel Cohort Markers.......................................... 30
Figure 3: Key molecular differences between adult and pediatric cancers ............................................. 31
Figure 4: Study CAN2002: Analysis Cohorts and Populations................................................................ 37
Figure 5: Instructions for up-titration of erdafitinib based on serum phosphate levels ............................ 55
Figure 6: Molecular Screening Approaches............................................................................................. 76
Figure 7: Interim Analyses for the Broad Panel Cohort ........................................................................... 98

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
7
Status: Approved, Date: 22 February 2023
PROTOCOL AMENDMENTS
DOCUMENT HISTORY
Document 
Date
Amendment 6 
22 February 2023
Amendment 5 
10 November 2022
Amendment 4 
29 August 2022
Amendment 3 
12 Aug 2021
Amendment 2 
19 Aug 2020
Stand-alone National Disaster Appendix  
08 Jun 2020
Amendment 1 
15 Aug 2019
Original Protocol 
25 Jun 2019
Amendment 6 (22 February 2023)
Overall Rationale for the Amendment:  To modify the end of study definition and introduce a long-term
extension phase for continued treatment with erdafitinib, with limitation of data collection, after study
completion.
The changes made to Clinical Protocol 42756493CAN2002 as part of Protocol Amendment 6 are listed
below, including the rationale for each change and a list of all applicable sections. Changes made in
previous protocol amendments are listed in Section 10.14 Appendix 14: Protocol Amendment History.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis, Overall
Design, Intervention
Groups and Duration;
1.3 Schedule of Activities:
For Adults (≥18 years of
age [footnote a]);
1.4 Schedule of Activities:
For Children and
Adolescents (≥6 to <18
Years of Age [footnote b])
4.1 Overall Design;
4.3 Justification for Dose;
5.5 Study Completion (ie,
End of Data Collection
Timepoint) and End of
Study
5.5.1 Study Completion
(i.e. End of Data
Collection Timepoint)
Definition;
5.5.2 End of Study
Definition –Overall Study;
6.1 Study Drug
Administered;
6.7 Study Drug After
Study Completion.
8.1.2 Treatment Phase;
8.1.3 End-of-Treatment
Visit;
8.1.4 Follow-Up Phase;
9.4.3.2 Final Analysis;
Study completion is defined as the end of data
collection timepoint, ie, the date at which  the
clinical cutoff for the primary analysis has been
achieved. For subjects <18 years of age, the end
of data collection is defined as the timepoint
when the most recently enrolled pediatric subject
still participating in the study has 6 months of
follow-up or the last follow-up visit of the last
pediatric subject, whichever occurs first.
The end of study is defined as the time when the
last subject receives the last dose of study drug on
the study.
The title of Section 5.5, End of Study Definition,
was revised to Study Completion (ie, End of Data
Collection Timepoint) and End of Study.
The title of Section 5.5.1, End of Study Definition
Per Cohort, was revised to Study Completion (i.e.
End of Data Collection Timepoint) Definition.
In the applicable sections, it was clarified that the
subject follow-up and data collection will end
once the end of data collection timepoint has been
achieved (removed “for a cohort”). Subjects in
the treatment phase who continue to derive
benefit from study treatment will be allowed to
receive study treatment in the LTE Phase and
only serious adverse events will be reported in the
company safety repository.
To revise the end of study
definition, study completion
definition (ie, end of data
collection timepoint definition),
and to modify data collection
during continued treatment
with erdafitinib after the study
data collection timepoint.
To clarify monitoring of only
serious adverse events for
subjects continuing study
treatment (ie, in the LTE
Phase).

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
8
Status: Approved, Date: 22 February 2023
Section Number 
and Name
Description of Change 
Brief Rationale
10.3.1 Regulatory and
Ethical Considerations
(Long-term Extension and
Post-trial Access)
1.2 Schema (Figure 1); 
1.3 Schedule of Activities: 
For Adults (≥18 Years of 
Age); 
1.4 Schedule of Activities: 
For Children and 
Adolescents (≥6 to <18
Years of Age);
5.5.1 Study Completion
(i.e. End of Data
Collection Timepoint)
Definition;
6.7 Study Drug After
Study Completion;
8.1.3 End-of-Treatment
Visit;
10.3.1 Regulatory and
Ethical Considerations
(Long-Term Extension and
Post-trial Access);
10.13 Appendix 13 Long-
term Extension Phase
Added Appendix 13 for the Long-term 
Extension (LTE) Phase. 
In the applicable sections, added reference to 
Appendix 13 for details on the LTE phase. 
Additional instruction for
continued treatment with
erdafitinib after the end of the
data collection timepoint
(termed the LTE Phase with
Amendment 6) was provided.
1.4 Schedule of Activities: 
For Children and 
Adolescents (≥6 to <18 
Years of Age)
Timepoints removed and added that the PRO 
measurements are discontinued with 
Amendment 6. 
PRO measurements after this
timepoint are no longer
necessary.
8.2 Efficacy Assessments 
Removed with Amendment 6, the IRC central 
read for confirmation of progression. 
IRC confirmation of
progression of disease is no
longer required.
1.4 Schedule of Activities: 
For Children and 
Adolescents (≥6 to <18 
Years of Age);
3. Objectives and 
Endpoints; 
9.4.8 Other Analyses 
Removed acceptability and palatability of 
erdafitinib as an exploratory objective and 
Palatability VAS as an assessment. 
Removed Section 9.4.8 (Other Analyses) and
Appendix 10.13 (Pediatric Cohort Medicine
Palatability Testing).
Palatability VAS assessment is
no longer required for children
included in the study.
Throughout the protocol 
Minor corrections, formatting or spelling 
changes were made. 
Minor errors, formatting or
spelling errors were noted

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
9
Status: Approved, Date: 22 February 2023
1. 
PROTOCOL SUMMARY
1.1. 
Synopsis
A Phase 2 Study of Erdafitinib in Subjects with Advanced Solid Tumors and FGFR Gene Alterations
Erdafitinib (JNJ-42756493) is a selective and potent pan fibroblast growth factor receptor (FGFR) tyrosine
kinase inhibitor with  demonstrated clinical activity in subjects with solid tumors identified to have
alterations in the FGFR pathway.
OBJECTIVES
Primary Objective (Broad Panel Cohort and Core Panel Cohort)
 
To evaluate the efficacy of erdafitinib in terms of overall response rate (ORR) as assessed by the
Independent Review Committee (IRC) in subjects with advanced solid tumors with target FGFR
mutations and any gene fusions (Broad Panel Cohort), or in a pre-specified subgroup of subjects with
a selected panel of FGFR markers (Core Panel Cohort), or in both cohorts.
Primary Objective (Pediatric Cohort)
 
To evaluate the efficacy of erdafitinib in terms of ORR as assessed by the IRC in pediatric subjects
with advanced solid tumors with FGFR mutations, any gene fusions or FGFR internal tandem
duplication (Pediatric Cohort), including adolescent subjects with target FGFR mutations and any gene
fusions
Secondary Objectives
 
To evaluate the efficacy of erdafitinib, in terms of ORR, as assessed by the investigator
 
To evaluate the efficacy of erdafitinib in terms of duration of response (DOR)
 
To evaluate other measures of efficacy including disease control rate (DCR), clinical benefit rate
(CBR), progression-free survival (PFS), and overall survival (OS)
 
To evaluate erdafitinib pharmacokinetics (PK)
 
To evaluate safety and tolerability of erdafitinib
 
To evaluate health-related quality of life (HRQoL)
Cholangiocarcinoma Expansion Cohort
 
To evaluate the efficacy and safety of erdafitinib in subjects with cholangiocarcinoma with target FGFR
mutations and any gene fusions
OVERALL DESIGN
This is a Phase 2, open-label study of the efficacy and safety of erdafitinib in subjects ≥6 years of age with
advanced solid tumors (other than urothelial tumors) and FGFR gene alterations. Subjects ≥12 years of age
with target FGFR mutations or any FGFR gene fusions will be enrolled into the Broad Panel Cohort. Target
FGFR mutations include select mutations based on predicted likelihood for pathogenicity with preclinical
sensitivity to erdafitinib, or those with clinical or correlative evidence supporting inclusion. A subgroup of
subjects in the Broad Panel Cohort with a select panel of pre-specified FGFR markers will be identified as
the Core Panel Cohort (for analysis only). While the Broad Panel Cohort consists of target FGFR mutations
and any fusions, the Core Panel Cohort consists of a select subset of FGFR mutations or fusions with known
observed clinical activity in previous studies and/or with a high level of recurrence. Subjects with any other

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
10
Status: Approved, Date: 22 February 2023
FGFR mutations that are not captured in the Broad Panel Cohort will be included in the study as the
Exploratory Cohort. A separate Cholangiocarcinoma Expansion Cohort will enroll subjects with target
FGFR mutations or any FGFR gene fusion once the Broad Panel Cohort has reached the cap of
approximately 30 subjects for cholangiocarcinoma. A Pediatric Cohort will enroll all subjects ≥6 to
<18 years of age with locally advanced or metastatic solid tumors harboring FGFR alterations who have
either progressed following prior therapies and who have no acceptable standard therapies, or who have a
newly-diagnosed solid tumor and who have no acceptable standard therapies. Adolescent subjects enrolled
in the Broad Panel Cohort (≥12 to <18 years) will be analyzed as part of the Broad Panel Cohort and the
Pediatric Cohort.
The Screening Phase will start with the Molecular Eligibility Screening Period. Subjects with study-eligible
FGFR alterations may be identified by central next-generation sequencing (NGS) from tissue sample, or
based on locally performed and commercial testing from tissue or blood (NGS tests, direct digital counting
methods, or the Qiagen therascreen® FGFR reverse transcription polymerase chain reaction [RT-PCR]
test). Starting with Amendment 4, only local reports will be used for molecular screening. The Full-study
Screening Period will occur after the completion of prior treatment and documentation of disease
progression for subjects who meet the molecular screening criteria. The Treatment Phase will continue until
disease progression, intolerable toxicity, withdrawal of consent, decision by the investigator to discontinue
treatment, or the end of data collection timepoint has been achieved. The post-treatment Follow-up Phase
will extend from the End-of-Treatment Visit until the subject has died, withdraws consent, is lost to follow-
up, or study completion, whichever comes first.
Study completion and end of study are distinct timepoints. Study completion is defined as the end of data
collection timepoint, ie, the date at which the clinical cutoff for the primary analysis has been achieved. For
subjects <18 years of age, the end of data collection is defined as the timepoint when the most recently
enrolled pediatric subject still participating in the study has 6 months of follow-up or the last follow up visit
of the last pediatric subject, whichever occurs first. End of study is defined as the time when the last subject
receives the last dose of study drug on the study.
Upon initiation of the LTE Phase, participation in the Follow-Up Phase will end and study data collection
will conclude in the clinical database; and only serious adverse events will be reported to the company
safety repository.
NUMBER OF SUBJECTS
Approximately 280 subjects ≥12 years of age with FGFR genetic alterations will be enrolled in the Broad
Panel Cohort (approximately 240 subjects) and the Exploratory Cohort (approximately 40 subjects). An
additional approximately 30 subjects will be enrolled in the Cholangiocarcinoma Expansion Cohort. The
Pediatric Cohort (approximately 26 subjects) consisting of children or adolescent subjects ≥6 to <18 years
of age with locally advanced or metastatic solid tumors will enroll 20 children or adolescent subjects who
have progressed following prior therapies and who have no acceptable standard therapies, and
approximately 6 additional children or adolescent subjects who have a newly-diagnosed solid tumor and
who have no acceptable standard therapies. Adolescent subjects enrolled in the Broad Panel Cohort (≥12
to <18 years) will be analyzed as part the Broad Panel Cohort and the Pediatric Cohort.
INTERVENTION GROUPS AND DURATION
Subjects will take erdafitinib orally once daily for 21 days on a 21-day cycle until disease progression,
intolerable toxicity, withdrawal of consent, decision by the investigator to discontinue treatment, or the end
of data collection timepoint has been achieved. Adults (aged 18 years and older for dosing purposes) and
adolescent subjects aged ≥15 to <18 years will start with an erdafitinib dose of 8 mg with possible up-
titration to 9 mg based on Cycle 1 Day 14 serum phosphate levels. Adolescent subjects aged ≥12 to <15
years will start with an erdafitinib dose of 5 mg with possible up-titration to 6 mg or further to 8 mg based
on Cycle 1 Day 14 and Cycle 2 Day 7 serum phosphate levels. Children aged ≥6 to <12 years will start with

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
11
Status: Approved, Date: 22 February 2023
an erdafitinib dose of 3 mg with possible up-titration to 4 mg or further to 5 mg based on Cycle 1 Day 14
and Cycle 2 Day 7 serum phosphate levels.
EVALUATIONS
Assessment of response will be performed according to Response Evaluation Criteria in Solid Tumors
(RECIST, version 1.1) or Response Assessment in Neuro-Oncology (RANO) by the IRC and investigators.
Pharmacokinetic assessments (plasma concentrations of erdafitinib and alpha-1-acid glycoproteins, total
protein, and fraction unbound, if required, using venous blood samples), biomarker assessments (molecular
screening to determine eligibility for the study; and possibly exploratory deoxyribonucleic acid (DNA),
ribonucleic acid (RNA), and protein analyses using archival or fresh biopsy tissue and blood (circulating
tumor [ct]DNA) for exploratory research), patients’ health-related QoL assessments, and safety
assessments (including adverse event [AE] reports and results of vital sign measurements,
electrocardiograms [ECGs], physical examinations, clinical laboratory tests, performance status
assessment, and ophthalmologic examinations) will be conducted as described on the Schedule of
Activities. Additional safety assessments for children and adolescent subjects include radiographic (growth
plate assessment and bone age) imaging, dual-energy X-ray absorptiometry (DEXA) scan for bone
densitometry, and clinical laboratory tests for thyroid stimulation hormone (TSH), total triiodothyronine
(T3), and free thyroxine (T4) and insulin-like growth factor 1 (IGF-1), and will be conducted as described
on the Schedule of Activities.
STATISTICAL METHODS
For the Broad Panel Cohort, the primary endpoint is ORR based on RECIST v1.1. or RANO as assessed
by the IRC and will be calculated with a 95% 2-sided exact confidence interval (CI). The primary endpoint
will be analyzed using data from the Treated Population (defined as all subjects [FGFR+] who receive at
least 1 dose of study drug) in the Broad Panel Cohort and the Core Panel Cohort. An error-spending function
approach will be used to split the significance level for the Broad Panel Cohort and the Core Panel Cohort.
The secondary  endpoints include ORR by investigator assessment, DOR, DCR, CBR, PFS, OS, PK
exposure parameters, incidence and severity of AEs, and PROs. The ORR assessed by the investigator will
be analyzed in the same way as the ORR assessed by the IRC. The distributions of DOR, PFS and OS will
be summarized using Kaplan-Meier estimates and the estimated median will also be reported along with a
95% CI. The PRO assessments will be analyzed with descriptive summaries (ie, mean, standard deviation
including change from baseline) at each assessment time point. The Pediatric Cohort will have the same
primary and secondary endpoints as the Broad Panel Cohort; subjects in the Pediatric Cohort will be
evaluated separately from the Broad Panel Cohort. The Cholangiocarcinoma Expansion Cohort will also
be evaluated separately from the Broad Panel Cohort.
Three interim futility analyses are planned when 30%, 50%, and 70% of the subjects in the Broad Panel
Cohort (ie, approximately 60, 100, and 140 subjects) have been treated and are considered response-
evaluable by investigator assessment, irrespective of the tumor histologies and the distribution among the
tumor histologies. The interim analyses for futility will be based on the ORR assessed by investigator using
a Bayesian hierarchical model (BHM), implemented in FACTS v6.2 Enrichment Design –Dichotomous.
In addition, an interim efficacy analysis will be conducted for the Broad Panel Cohort at the same time as
the second interim futility analysis.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
12
Status: Approved, Date: 22 February 2023
1.2. 
Schema
Figure 1: 
Schematic Overview of the Study
Note: The LTE phase is not included in the schematic (see Appendix 13).
a See Section 8.1.1 for information regarding consent during the screening periods. During the Molecular Eligibility Screening Period, either the
central or local screening approach may be followed as described in Section 8.1.1.1. Starting with Amendment 4, only local reports will be used
for molecular screening.
b See Section 6.1 for detailed information regarding titration of erdafitinib based on serum phosphate levels. Treatment is continued until progressive
disease, intolerable toxicity, consent withdrawal, or investigator decision to stop treatment. See Section 8.2.2 for continuation of treatment after
progressive disease. Note that children and adolescent subjects remain under the titration and dosing schedule under which they were enrolled.
c Up to 30 subjects in each tumor histology will be enrolled in the Broad Panel Cohort with the possibility of increasing the number of subjects in
a specific tumor histology upon decision by the sponsor’s Data Review Committee. The rationale for biomarker selection is described in
Section 4.2.1.
d Subjects with target FGFR mutations are eligible for enrollment in the Broad Panel Cohort. The List of Target FGFR Mutations (over 30 validated
FGFR mutations) is provided in Section 10.11.
e Subjects with any FGFR gene fusion are eligible for enrollment in the Broad Panel Cohort. FGFR gene fusions must have an intact FGFR kinase
domain. FGFR gene identifiers for reference are provided in Section 5.1, Criterion 2.
f Subjects with FGFR mutations that do not meet the Broad Panel Cohort criteria (ie, not on the List of Target FGFR Mutations) are eligible for
enrollment in the Exploratory Cohort.
g A separate Cholangiocarcinoma Expansion Cohort will enroll subjects with target FGFR  mutations or any FGFR gene fusion once the Broad
Panel Cohort has reached the cap of approximately 30 subjects for cholangiocarcinoma.
h The Pediatric Cohort will enroll 20 children and adolescent subjects who have progressed following prior therapies and who have no acceptable
standard therapies, and approximately 6 additional children and adolescent subjects who have a newly-diagnosed solid tumor and who have no
acceptable standard therapies. Adolescent subjects enrolled in the Broad Panel Cohort (≥12 to <18 years) will be analyzed as part of the Broad
Panel Cohort and the Pediatric Cohort; therefore 240 subjects in the Broad Panel Cohort can include subjects from Pediatric Cohort.
i Subjects with FGFR mutations (exclusive of valine gatekeeper and resistance alterations), any FGFR gene fusion, or FGFR internal tandem
duplication are eligible for enrollment in the Pediatric Cohort (see Section 5.1, Criterion 2).

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
25
Status: Approved, Date: 22 February 2023
2. 
INTRODUCTION
Erdafitinib (JNJ-42756493) is a selective and potent pan fibroblast growth factor receptor (FGFR)
1-4 inhibitor with demonstrated clinical activity in subjects with solid tumors identified to have
alterations in the FGFR pathway. In the United States (US), erdafitinib (BALVERSATM) was
approved on 12 April 2019 for the treatment of adult patients with locally advanced or metastatic
urothelial carcinoma, that has susceptible FGFR3 or FGFR2 genetic alterations, and has
progressed during or following at least 1 line of prior platinum-containing chemotherapy,
including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. This
Phase 2, open-label study will evaluate the safety and efficacy of erdafitinib in subjects with
advanced solid tumors (other than urothelial tumors), and FGFR gene alterations.
The term “sponsor” used throughout this document refers to the entities listed in the Contact
Information page(s), which will be provided as a separate document.
2.1. 
Study Rationale
FGFR gene alterations (mutations and fusions) are proposed to be oncogenic drivers in many solid
tumors. Review of literature and genetic databases reveal multiple solid tumor histologies with
FGFR mutations and fusions that may be plausible targets for treatment with erdafitinib. FGFR
alteration frequency and observed alterations (mutations versus fusions) vary across tumor types,
eg, FGFR mutations are more common in urothelial carcinoma while FGFR fusions are more
frequently observed in glioblastoma. The common result of FGFR alterations across tumor types
is activated FGFR signaling, providing rationale that patients with FGFR alterations may benefit
from erdafitinib treatment. The antitumor effect of erdafitinib was observed in subjects with
urothelial cancer with select FGFR alterations in both Phase 1 and Phase 2 studies, and clinical
activity has also been observed in subjects with cholangiocarcinoma (Chen 2018). This study
targets the underlying altered biology of FGFR-driven tumors irrespective of the solid tumor
histology subtype.
Patients with solid tumors with a significant frequency of FGFR alterations (Table 1) have a dismal
prognosis in advanced disease and limited efficacy with standard of care options in the recurrent,
metastatic setting; especially for second-line therapy or beyond. Glioblastoma multiforme (GBM)
is a solid tumor with a high frequency of FGFR alterations (~21%). Approved second-line GBM
therapies include bevacizumab (US) or lomustine (European Union [EU]) with a median
progression-free survival (PFS) of 4 months and a median survival of 9 months (Friedman 2009).
Squamous cell carcinomas of the head and neck (ie, HNSCC) have an FGFR alteration frequency
of 9%, and HNSCC patients with recurrent or metastatic disease on second-line therapy have a
median survival between 7 to 8 months and a median PFS of 2.1 months with programmed
death-ligand 1 (PD-L1) therapies (Ferris 2016). Cholangiocarcinoma is a low prevalence tumor
type with a notable frequency of FGFR alterations (11%) for which there are no approved
second-line therapies. Patients with solid tumors in which FGFR alterations are most frequently
observed (Table 1) have poor outcomes and limited therapeutic options; thus, there remains a high
unmet need for additional treatments in the metastatic setting. In general, for pediatric subjects, no
standard of care has been established for relapsed and or refractory disease in these tumor types,

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
26
Status: Approved, Date: 22 February 2023
which represents an unmet medical need. Taken together, the common underlying biology of
FGFR-altered tumors in conjunction with the high unmet need for additional therapeutic options
for patients with these tumors provide a strong rationale for targeting the FGFR-positive
population across solid tumors with erdafitinib.
2.2. 
Background
In the US, erdafitinib (BALVERSATM) was approved on 12 April 2019 for the treatment of adult
patients with locally advanced or metastatic urothelial carcinoma that has susceptible FGFR3 or
FGFR2 genetic alterations and has progressed during or following at least 1 line of prior platinum
containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum
containing chemotherapy. The label also notes that patients are selected for therapy based on an
FDA-approved companion diagnostic, ie, the QIAGEN therascreen® FGFR RGQ RT PCR Kit
that was also approved by the Agency on 12 April 2019. Detailed information regarding
erdafitinib, as well as the role of FGFR and FGFR alterations in solid tumors is provided in this
section.
2.2.1. 
Erdafitinib
Erdafitinib is an oral pan-FGFR tyrosine kinase inhibitor shown to have in vivo antitumor activity
in mouse xenograft models of FGFR-driven gastric, bladder, and non-small cell lung cancer
(NSCLC) tumor models, and in patient-derived xenografts from squamous NSCLC, gastric, breast,
and hepatocellular tumors.
In humans, erdafitinib exhibited a dose-related increase in the maximum plasma drug
concentration (Cmax) and area under the curve (AUC) and time-independent pharmacokinetics
(PK) within the dose range of 0.5 mg to 12 mg, both after single and multiple daily dosing. Median
time to maximum concentration observed ranged from 2 to 4 hours (erdafitinib as capsule).
Relative bioavailability was comparable under fed and fasted conditions. Erdafitinib is highly
bound to plasma proteins such as α1-acid glycoprotein (α1-AGP). Free fractions of erdafitinib in
human plasma were small (average~0.36%). Erdafitinib is a P-glycoprotein (P-gp) substrate.
An in vitro metabolism study in human liver microsomes and hepatocytes showed major
involvement of cytochrome P 450 (CYP) enzymes CYP2C9 and CYP3A4. Long terminal phase
half-life of erdafitinib (>50 hours) in plasma was observed resulting in approximately 3-fold
accumulation of Cmax and AUC following multiple daily dosing.
In a Phase 1 study (Study 42756493EDI1001, n=187), the antitumor effect of erdafitinib was
observed in subjects with urothelial cancer with selected FGFR aberrations, as well as other solid
tumors. For all subjects with relapsed/refractory urothelial cancer, the overall response rate (ORR)
across dose levels was 40.0% (12/30 subjects). At the 9 mg dose level, ORR was
70.0% (7/10 subjects) for response-evaluable subjects with urothelial cancer who harbored
selected FGFR aberrations. The most frequently reported adverse events (AEs) were
hyperphosphatemia (65%), dry mouth (46%), asthenia (45%), stomatitis (39%), constipation
(37%), and decreased appetite (34%).

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
27
Status: Approved, Date: 22 February 2023
In a Phase 2a Study (Study 42756493LUC2001, based on preliminary data from the
cholangiocarcinoma cohort with a clinical cut-off date of 25 March 2019), the antitumor effect of
erdafitinib was observed among subjects with any FGFR alterations (ORR, 46.7% [7/15 subjects];
median duration of response [DOR], 7.1 months; disease control rate [DCR], 80.0%
[12/15 subjects]; median PFS, 5.6 months [13/15 subjects]) and an even greater antitumor response
was observed among the 9 evaluable subjects with FGFR2 or FGFR 3 fusions (ORR, 66.7%
[6/9 subjects]; median DOR, 7.3 months; DCR, 100.0% [9/9 subjects]; median PFS, 12.7 months
[7/9 subjects with events]). In addition, for the 6 subjects with FGFR2 and FGFR 3 mutations, the
ORR was 16.7% (1/6 subjects) and the DCR was 50.0% (3/6 subjects).
In a global Phase 2 study (Study 42756493BLC2001, n=210), the antitumor effect of erdafitinib
was demonstrated in subjects with locally advanced or metastatic urothelial cancer who also had
select FGFR alterations. The confirmed ORR for chemo-relapsed/refractory subjects who were
treated in the erdafitinib 8-mg daily regimen with pharmacodynamically guided up-titration to
9-mg daily  (N=87) was 40.2% based on investigator assessment and 32.2% by Independent
Review Committee (IRC) assessment. The most frequently reported AEs were hyperphosphatemia
(77%), stomatitis (58%), diarrhea (51%), and dry mouth (46%). For the most comprehensive
nonclinical and clinical information regarding erdafitinib, refer to the latest version of the
Investigator’s Brochure.
A subprotocol of the NCI-Children’s Oncology Group (COG) Pediatric Molecular Analysis for
Therapy Choice (MATCH) Trial APEC1621Ba is currently enrolling pediatric subjects ≥1 and
≤21 years of age with recurrent or refractory solid tumors (including non-Hodgkin lymphomas,
histiocytoses, and central nervous system (CNS) tumors) harboring specified activating mutations
of the FGFR1/2/3/4 pathway for treatment with erdafitinib. The primary endpoint is ORR. Subjects
will remain on treatment until progression of disease or drug-related toxicity requiring
discontinuation of treatment; otherwise, a subject may remain on erdafitinib for 2 years. The study
began 30 November 2017 and approximately 20 subjects are expected to be enrolled. As of
, no new safety signals from the 
 subjects enrolled (  subjects aged between
≥1 and <12 years of age and 
subjects aged between ≥12 and <21 years of age) were reported
from this ongoing study.
2.2.2. 
The Role of Fibroblast Growth Factor Receptor
The FGFRs 1 to 4 are a family of highly conserved, widely distributed transmembrane tyrosine
kinase receptors (Parker 2014). Binding of fibroblast growth factor to FGFR results in receptor
dimerization and phosphorylation of the kinase domain, with activation of subsequent downstream
signaling pathways regulating key cellular processes, including differentiation, proliferation,
survival, migration, and angiogenesis (Dienstmann 2014).
a    The National Cancer Institute (NCI) Molecular Analysis for Therapy Choice (MATCH) APEC1621B study, Phase
2 Subprotocol of JNJ-42756493 (Erdafitinib) in Patients with Tumors Harboring FGFR1/2/3/4 Alterations; this is
the sponsor’s collaborative study with NCI and the Children’s Oncology Group (COG).
CCI
C
CI
CCI
C
C

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
28
Status: Approved, Date: 22 February 2023
Deregulation of FGFR signaling has been implicated in many forms of human malignancies
(Babina 2017, Dienstmann 2014, Touat 2015). FGFR signaling can be aberrantly activated in
tumor cells in several ways including amplification, gene fusion, or mutation. Mutations occurring
in the extracellular or transmembrane domains of the receptor result in ligand-independent
dimerization and constitutive activity. FGFR gene fusions induce aberrant activation via
substitution of the C-terminal regulatory domain of FGFR with protein-protein interaction
modules of the fusion partner, leading to ligand-independent dimerization and activation of FGFR
(Katoh 2019). FGFR alterations have been associated with neoplastic progression and tumor
vascularization in multiple cancer types, including breast, lung, prostate, endometrial, gastric, and
urothelial carcinoma (Parker 2014, Katoh 2019). Therefore, targeting FGFRs with a small
molecule kinase inhibitor is a logical development strategy.
2.2.3. 
Fibroblast Growth Factor Receptor Alterations in Solid Tumors
FGFR alterations in adult and pediatric solid tumors are discussed in the following subsections.
Further detail regarding tumor histologies selected for central screening and the inclusion of any
FGFR mutation or fusion positive tumor histology based on local testing is provided in
Section 8.1.1.1. Starting with Amendment 4, only local reports will be used for molecular
screening.
Adult Solid Tumors
FGFR alterations including gene amplification, mutation, and fusion are observed across many
types of cancer, with FGFR amplification being the most commonly observed event (Katoh 2019).
Although FGFR gene amplifications are frequent, clinical activity with FGFR kinase inhibitors
like erdafitinib has been most clearly observed in patients with FGFR mutations and gene fusions.
FGFR mutations and fusions have been reported in breast cancer, urothelial cancer, NSCLC,
cholangiocarcinoma, gynecological cancers, and other tumor histologies.
For some tumor histologies, the predominant FGFR alteration (ie, fusion vs. mutation) may be
tissue specific. For example, FGFR fusions are more prevalent (than mutations) in glioblastoma
and cholangiocarcinoma, while FGFR mutations are more prevalent (than fusions) in urothelial
and endometrial cancers (Katoh 2019, Knowles 2015, Babina 2017).
Target FGFR mutations and FGFR fusions, FGFR mutations and fusions predicted to likely be
pathogenic based on genomic features, as defined in Study CAN2002 (see Section 4.2.1), are found
across multiple tumor histologies. Table 1 lists approximate frequencies of total (unfiltered), and
target FGFR mutations and gene fusions based on filtering of alterations identified in the TCGA
(The Cancer Genome Atlas) and GENIE (the AACR Project Genomics Evidence Neoplasia
Information Exchange) genomic databases. For pancreatic cancer, although no target FGFR
alterations were observed in TCGA and GENIE databases, clinical experience supports the
presence of target FGFR alterations (ie, FGFR fusions) in this histology.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
29
Status: Approved, Date: 22 February 2023
Table 1: Frequency of FGFR Mutations and Fusions in Advanced Cancer
GENIE Database Estimates
Tumor Type 
N 
RAGNAR Eligible
FGFR variants %1
Cholangiocarcinoma 
1111 
7.65
Head and Neck Squamous Cell Carcinoma 
1076 
2.51
Low Grade Glioma 
1157 
2.33
High Grade Glioma 
1986 
2.06
Cervix  
522 
1.92
Endometrial Carcinoma 
3240 
1.82
Lung Squamous Cell Carcinoma 
1134 
1.68
Cancer of Unknown Primary  
2669 
1.09
Colorectal Adenocarcinoma 
7451  
0.47
Invasive Breast Carcinoma2 
8367 
0.45
Cervical Adenocarcinoma 
241 
0.41
Stomach Adenocarcinoma 
746 
0.40
Salivary Carcinoma 
597 
0.34
Lung Adenocarcinoma 
8127 
0.25
Soft Tissue3 
3778 
0.16
Pancreas 
3805 
0.16
Renal Cell Carcinoma 
1591 
0.13
1. AACR-GENIE database accessed June 2021
2. In CAN2002 ER/PR positive only
3. Soft Tissue cancers (in AACR-GENIE database) including: Dendritic Cell Sarcoma, Epitheloid Fibrosarcoma,
Liposarcoma, Myxoma, Rhabdomyosarcoma
Pediatric Solid Tumors
FGFR alterations have also been observed in pediatric cancers.
The screening protocol for the NCI-COG Pediatric MATCH study identified 422 pediatric patients
(aged 1 to 21 years) with treatment-refractory or recurrent cancers between 24 July 2017 and
31 December 2018: 71% solid tumors, 24% CNS tumors, and 5% lymphomas/histiocytoses
(Parsons 2019). The percentage of subjects with actionable mutations was similar between younger
(35%, <12 years of age) and older (25%, ≥12 years of age) subjects and 5 subjects were reported
with FGFR1 alterations.
While the incidence and prevalence of specific types of solid tumors differs between adult and
pediatric subjects, FGFR alterations are observed in both populations which may be candidates for
targeted treatment with erdafitinib. Observed differences between adult and pediatric cancers

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
30
Status: Approved, Date: 22 February 2023
indicate that the pediatric FGFR-altered subject population may be better served with customized,
broader FGFR molecular eligibility criteria.
The list of Broad Panel Cohort eligible FGFR mutations was defined based on genomic datasets
derived predominantly from adult subjects. Broad Panel Cohort eligible FGFR mutations are
observed in the pediatric population (Table 2). However, a significant number ofpediatric tumors
have mutations not included on the Broad Panel Cohort list. This list was determined by assessing
the FGFR alteration landscape of the 8 most common pediatric tumors (Table 2). Although 9 of
185 FGFR mutations observed in the pediatric population are present in the Broad Panel Cohort
(Figure 2), the bulk of pediatric mutations are not represented.
Table 2: 
FGFR Mutations and Fusions Observed in Common Pediatric Tumors
Abbreviation 
Histology  
Patients 
FGFR+ 
% 
Broad Panel Cohort
Representation (%)
GBM
Glioblastoma multiforme
267
33 
8
LGG
Low Grade Glioma
1179
20 
10
PA
Pilocytic Astrocytomas
241
14 
9
RMS
Rhabdomyosarcomas
321 
13 
8
WLM
Wilms’ tumor
127
6 
1
NBL
Neuroblastoma
394
5 
1
EWS
Ewing Sarcoma
268
3
MDB  
Medulloblastoma 
199 
1
FGFR=fibroblast growth factor receptor
FoundationInsights database accessed June 2020.
Note that the FoundationInsights database may underrepresent fusions due to limitation of DNA-based profiling.
Figure 2 shows the overlap of the pediatric landscape of FGFR mutations in 8 common pediatric
tumors with the list of Broad Panel Cohort eligible alterations derived from adult data. Notably,
compared with the >8,000 mutations observed across adult tumors, the most common pediatric
tumors exhibited 185 distinct FGFR mutations.
Figure 2: 
Overlap of Pediatric Alterations with Broad Panel Cohort Markers

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
31
Status: Approved, Date: 22 February 2023
FGFR alteration frequencies for 8 of the most frequently observed pediatric tumors were assessed
utilizing the FoundationInsights database. The table below lists the percent of pediatric subjects
with FGFR mutations and fusions and the proportion of subjects eligible for the Broad Panel
Cohort.
Additional considerations supportive of a custom cohort for pediatric tumors are the smaller
landscape of FGFR alterations in pediatric tumors, the lower overall mutation burden in pediatric
tumors compared to adults, and that driver alterations are largely mutually exclusive in the
pediatric population. Gröbner et al (Gröbner 2018), analyzed the landscape of genomic alterations
across childhood cancers compared with adults. As anticipated, the burden of somatic alterations
was higher in the adult population compared to pediatric patient tumors, with mutation frequencies
14 times lower in the pediatric cancers. Significantly mutated genes were largely mutually
exclusive across pediatric cancer types, highlighting the relevance of single-driver alterations in
pediatric cancers versus the adult population where co-alterations are more frequent. Notably,
FGFR1 was reported as one of 77 significantly mutated genes in pediatric cancers. In contrast,
FGFR1 alterations are relatively rare in the adult population where FGFR2 and FGFR3 alterations
are more common.
Recurrence of alterations, within or across tumor types, was a key factor in determining likely
pathogenicity in the Broad Panel Cohort based on adult genomic data. Recurrent FGFR mutations
are relatively rare in the pediatric population. Assessment of the 8 most common pediatric tumors
using the FoundationInsights database revealed that 91% of 185 FGFR alterations identified were
observed in ≤2 instances (Figure 3). Additionally, the Gröbner study (Gröbner 2018) reported 47%
of pediatric tumors had at least one significant mutation with 57% of those tumors having only
one significantly mutated gene; as opposed to the adult population where 93% of cancers had at
least one significantly mutated gene alteration and 76% had alterations in multiple significantly
mutated genes.
Figure 3: 
Key molecular differences between adult and pediatric cancers
Mut = mutation

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
32
Status: Approved, Date: 22 February 2023
These data indicate that a customized approach is warranted to best serve the pediatric
FGFR-altered subject population. Therefore, the molecular eligibility criteria selected for the
Pediatric Cohort differ from those of the Broad Panel Cohort (see Section 5.1).
2.3. 
Benefit-Risk Assessment
FGFR alterations have been shown to be associated with oncogenic potential in several tumor
histologies and have been observed across many tumor histologies. The patients with advanced
life-threatening disease and FGFR alterations who will be enrolled in this study will have already
failed at least one prior line of systemic therapy and have limited available treatment options. For
this group, there is unmet medical need due to the absence of available treatments at this stage of
their disease. Erdafitinib inhibits FGFR signaling in FGFR-driven tumors. In clinical studies,
erdafitinib treatment resulted in durable anti-tumor response. Corresponding DOR, PFS, and OS
endpoints predict clinical benefit for patients with locally advanced or metastatic urothelial cancer
who have FGFR alterations and have relapsed after platinum-based chemotherapy. The potential
risks of erdafitinib for adults include central serous retinopathy and hyperphosphatemia. In
addition to the risk for adults, risks for adolescents and children include the possibility of bone
growth abnormalities based on pre-clinical findings in rats and dogs (cartilage dysplasia) attributed
to the pharmacology of erdafitinib. In this study, to monitor bone growth in adolescents and
children (subjects younger than 18 years), radiographic imaging and bone densitometry will be
conducted as indicated on the Schedule of Activities for Children and Adolescents. Subjects
<6 years of age are not included in the study because an age-appropriate formulation of erdafitinib
is not currently available. The safety profile of erdafitinib was acceptable in the urothelial cancer
population; the profile was characterized by mostly mild to moderate eye, skin and nail disorders.
The events in the urothelial population were manageable with available medical measures,
temporary treatment interruption, or eventual dose reduction.
Taking into account the measures utilized to minimize risk to subjects in this study (eg, guidance
regarding blood volume in adolescents in Section 4.2.4, guidance for specific erdafitinib toxicities
in Section 6.6.1, prohibited medications in Section 6.5.2, precautions for concomitant medications
in Section 6.5.3, and monitoring of results of safety assessments in Section 8.3), the potential risks
identified in association with  erdafitinib are justified by the anticipated benefits that may be
afforded to patients with advanced solid tumors with FGFR gene alterations for whom there are
no available treatments, including subjects ≥6 years of age. More detailed information about the
known and expected benefits and risks of erdafitinib may be found in the Investigator’s Brochure.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
33
Status: Approved, Date: 22 February 2023
3. 
OBJECTIVES AND ENDPOINTS
Objectives 
Endpoints
Primary Objective (Broad Panel Cohort and Core Panel Cohort)
To evaluate the efficacy of erdafitinib in terms 
of ORR as assessed by the Independent 
Review Committee (IRC) in subjects with 
advanced solid tumors with target FGFR 
mutations and any gene fusions (Broad Panel
Cohort), or in a pre-specified subgroup of
subjects with a selected panel of FGFR
markers (Core Panel Cohort), or in both
cohorts.
The proportion of subjects who achieve a complete response (CR)
or partial response (PR) based on Response Evaluation Criteria in
Solid Tumors (RECIST, version 1.1) (RECIST v1.1.) or Response
Assessment in Neuro-Oncology (RANO) as assessed by IRC
Primary Objective (Pediatric Cohort)
To evaluate the efficacy of erdafitinib in terms 
of ORR as assessed by the IRC in pediatric 
subjects with advanced solid tumors with
FGFR mutations, any gene fusions, or FGFR
internal tandem duplication (Pediatric Cohort),
including adolescent subjects with target
FGFR mutations and any gene fusions
The proportion of subjects who achieve a CR or PR based on
RECIST v1.1 or RANO as assessed by IRC
Secondary Objectives
To evaluate the efficacy of erdafitinib, in 
terms of the ORR, as assessed by investigator 
The proportion of subjects who achieve a CR or PR based on
RECIST v1.1 or RANO as assessed by investigator
To evaluate the efficacy of erdafitinib in terms 
of DOR  
DOR: the duration from the date of initial documentation of a
response to the date of first documented evidence of progressive
disease (or relapse for subjects who experience CR during the
study) or death, whichever comes first. Data from subjects who
are progression-free and alive or have unknown status will be
censored at the last tumor assessment
To evaluate other measures of efficacy 
including DCR, clinical benefit rate (CBR), 
PFS, and overall survival (OS) 
 
DCR: the proportion of subjects with CR, PR or stable disease
(SD)
 
CBR: the proportion of subjects with CR, PR or durable SD
(defined as a duration of at least 4 months)
 
PFS: the duration from the date of the first dose of study drug
until the date of first documented evidence of progressive
disease (or relapse for subjects who experience CR during the
study) or death, whichever comes first. Data from subjects
who are progression-free and alive or have unknown status
will be censored at the last tumor assessment
 
OS: measured from the date of first dose of study drug to the
date of the subject’s death. If the subject is alive or the vital
status is unknown, the subject’s data will be censored at the
date the subject was last known to be alive
To evaluate erdafitinib PK 
PK exposure parameters. This endpoint includes pediatrics.
To evaluate safety and tolerability of 
erdafitinib
Incidence and severity of AEs
To evaluate Health-Related Quality of Life 
(HRQoL) 
Change from baseline in patient-reported health status and
physical functioning scales of the European Organisation for
Research and Treatment of Cancer Quality-of-life Questionnaire
Core 30 (EORTC-QLQ-C30; for subjects ≥18 years of age) or
Pediatric Functional Assessment Of Cancer Therapy-Brain (Peds
FACT-Br for subjects <18 years of age), Patient Global
Impression of Symptom Severity (PGIS), Patient Global
Impression of Change (PGIC), and European Quality of Life –
5 Dimensions-5 Levels (EQ-5D-5L).

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
34
Status: Approved, Date: 22 February 2023
Objectives 
Endpoints
Exploratory
To evaluate the efficacy of erdafitinib in 
subjects with advanced solid tumors in the 
Exploratory Cohort in terms of ORR
 
The proportion of subjects who achieve a CR or PR based on
RECIST v1.1 or RANO as assessed by the investigator
 
DOR, DCR, CBR, PFS, OS
Identify FGFR mutations and tumor 
histologies sensitive to erdafitinib from the 
Exploratory Cohort
FGFR mutations and tumor histologies with clinical response to
erdafitinib which are not represented in the Broad Panel Cohort.
To explore PK exposure-response 
relationships 
Quantitative relationship between PK exposure parameters,
pharmacodynamic (PD) parameters (serum phosphate), and
safety/efficacy parameters
To assess tumor-specific biomarkers (DNA, 
RNA, protein) in archival tumor samples, and 
possibly blood that potentially predict tumor
response or resistance to erdafitinib
Analysis of co-occurring genomic alterations from archival tumor
samples
To evaluate the relationship between CYP2C9 
polymorphism and PK of erdafitinib
Effect of CYP2C9 polymorphism on the PK of erdafitinib
To assess the distribution of erdafitinib in the 
cerebrospinal fluid (CSF) (when available) 
Erdafitinib concentration in CSF, ie, the CSF-to-plasma
concentration ratios
To collect Medical Resource Utilization data 
that may be used in future economic models 
Evaluation of all the health states generated by the EQ-5D-5L
utility and visual analog scale (VAS).
Refer to Section 8, Study Assessments and Procedures for evaluations related to endpoints.
Hypothesis
The primary hypothesis of this study is that treatment with erdafitinib orally once daily will
improve ORR with a target rate of 35% over a null rate of 15% in subjects with advanced solid
tumors that harbor target FGFR alterations in the Broad Panel Cohort, the Core Panel Cohort, or
both cohorts. Comparable response from erdafitinib treatment is expected in the pediatric and adult
study populations, ie, a 35% of ORR with a null hypothesis of 15% for ORR.
3.1. 
Cholangiocarcinoma Expansion Cohort
Objectives 
Endpoints
To evaluate the efficacy and safety of
erdafitinib in subjects with
cholangiocarcinoma with target FGFR
mutations and any gene fusions
Key efficacy endpoints will be evaluated including ORR assessed
by IRC/investigator, DOR, PFS, and OS
Incidence and severity of AEs
4. 
STUDY DESIGN
4.1. 
Overall Design
This is a Phase 2, open-label study of the efficacy and safety of erdafitinib in subjects with
advanced solid tumors (other than urothelial tumors) and FGFR gene alterations. A diagram of the
study design is provided in Section 1.2, Schema (Figure 1).

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
35
Status: Approved, Date: 22 February 2023
Approximately 280 subjects ≥12 years of age with FGFR genetic alterations will be enrolled in the
Broad Panel Cohort (approximately 240 subjects for 200 response-evaluable subjects) and the
Exploratory Cohort (approximately 40 subjects). An additional, approximately 30 subjects will be
enrolled in the Cholangiocarcinoma Expansion Cohort. A separate Pediatric Cohort (≥6 to
<18 years) will enroll 20 children or adolescent subjects who have progressed following prior
therapies and who have no acceptable standard therapies, and approximately 6 additional children
or adolescent subjects who have a newly-diagnosed solid tumor and who have no acceptable
standard therapies. Adolescent subjects enrolled in the Broad Panel Cohort (≥12 to <18 years) will
be analyzed as part the Broad Panel Cohort and the Pediatric Cohort.
Subjects will be instructed to take erdafitinib orally at approximately the same time each day, with
or without food, until disease progression, intolerable toxicity, withdrawal of consent decision by
the investigator to discontinue treatment, or the end of data collection timepoint has been achieved.
Instructions for subjects who have difficulties swallowing the tablets are provided in Section 6.1.
Adults (aged 18 years and older) and adolescent subjects aged ≥15 to <18 years will start with a
dose of 8 mg, once daily for 21 days on a continuous 21-day cycle. The dose will be up-titrated to
9 mg once daily based on Cycle 1 Day 14 serum phosphate levels. Adolescent subjects aged ≥12
to <15 years will start with an erdafitinib dose of 5 mg with possible up-titration to 6 mg or further
to 8 mg based on Cycle 1 Day 14 and Cycle 2 Day 7 serum phosphate levels. Children ≥6 to
<12 years of age will start with an erdafitinib dose of 3 mg with possible up-titration to 4 mg or
further to 5 mg based on Cycle 1 Day 14 and Cycle 2 Day 7 serum phosphate levels. See Section
4.3 for dose justification.
The Screening Phase will start with the Molecular Eligibility Screening Period during which
samples are screened for FGFR alterations by the central or local laboratory, or the presence of an
FGFR alteration is identified by an existing local report (that must be reviewed by the sponsor).
 Subjects from all solid tumor histologies (except bladder) with an eligible FGFR mutation
or fusion identified via local testing results (as outlined in Section 8.1.1) are considered
molecularly eligible for the study.
 Subjects with advanced solid tumors may receive central molecular screening if they have
received at least 1 line of systemic therapy and are anticipated to fulfill study eligibility
criteria within 6 months. Central molecular screening will be selective to the following
tumor histologies (see Figure 6): high-grade gliomas (eg, glioblastoma) and low-grade
gliomas; squamous cell head and neck cancers; soft tissue sarcoma; cholangiocarcinoma;
endometrial, cervical, and ovarian cancers; squamous NSCLC; renal cell cancer;
esophageal and gastric cancers; hormone-sensitive breast cancer (estrogen positive
[ER]/progesterone positive [PR]); hepatocellular carcinoma, pancreatic cancer, salivary
gland tumors, colorectal cancer, and thymic cancer/thymoma. Central screening for any
tumor type will be allowed for children and adolescent subjects or if a local report is
deemed insufficient. For enrollment in each tumor histology, the sample size is capped at
approximately 30 subjects. The tumor histology list for this cap, including a group of Other,
is pre-defined in Table 16.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
36
Status: Approved, Date: 22 February 2023
 Starting with Amendment 4, only local reports will be used for molecular screening.
The Full-study Screening Period will occur after the completion of prior treatment and
documentation of disease progression for subjects who meet the molecular screening criteria.
There must be no intervening therapy between documented disease progression and enrollment in
this study.
The Treatment Phase will continue until disease progression, intolerable toxicity, withdrawal of
consent, decision by the investigator to discontinue treatment, or the end of data collection
timepoint has been achieved. Treatment with erdafitinib may continue beyond the initial
demonstration of disease progression (according to criteria in Section 8.2.2.). The post-treatment
Follow-up Phase will extend from the End-of-Treatment Visit until the subject has died, withdraws
consent, is lost to follow-up, or the study ends (ie, the end of data collection timepoint has been
achieved), whichever comes first.
Once the end of data collection timepoint has been achieved, follow-up of subjects will end, and
data collection will conclude. Only serious adverse events will be reported in the company safety
repository. Subjects in the Treatment Phase who are continuing to derive benefit from study
treatment as determined by their investigator may continue to receive access to study treatment
either on this study, with only data collection of serious adverse events in the company safety
repository via LTE phase or a post-trial access program, when permitted by local regulations.
Subjects will be assessed for disease response by the IRC and by the investigator according to
RECIST 1.1 or RANO guidelines. Pharmacokinetic assessments (plasma concentrations of
erdafitinib and alpha 1-acid glycoproteins, total protein, and fraction unbound, if required, using
venous blood samples), biomarker assessments (molecular screening to determine eligibility for
the study; and possibly exploratory DNA, RNA, and protein analyses using archival or fresh
biopsy tissue and blood [ctDNA] for exploratory research), patients’ health-related QoL
assessments, and safety assessments (including AE reports and results of vital sign measurements,
electrocardiograms, physical examinations, clinical laboratory tests, Eastern Cooperative
Oncology Group [ECOG] performance status, and ophthalmologic examinations) will be
conducted as described on the Schedule of Activities. Additional safety assessments for children
and adolescent subjects include radiographic (growth plate assessment and bone age) imaging,
dual-energy X-ray absorptiometry (DEXA) scan for bone densitometry, and clinical laboratory
tests for thyroid stimulating hormone (TSH, T3, and T4) and insulin-like growth factor 1 (IGF-1)
(Section 8.3).
Statistical analyses will be primarily based on the Broad Panel Cohort of subjects with target FGFR
mutations and any gene fusion (described in Section 4.2.1). In addition, statistical analyses will be
performed in a subset of subjects from the Broad Panel Cohort whose tumors have select FGFR
alterations (listed in Section 9.3.1), this analysis subset is designated the Core Panel Cohort. No
formal hypotheses will be tested in the Exploratory Cohort. Subjects in the Pediatric Cohort will
be evaluated separately from the Broad Panel Cohort (Figure 4).

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
37
Status: Approved, Date: 22 February 2023
The Cholangiocarcinoma Expansion Cohort will also be evaluated separately from the Broad Panel
Cohort.
Figure 4: 
Study CAN2002: Analysis Cohorts and Populations
a. 
Adult subjects with FGFR alterations on the List of Target FGFR Mutations provided in Section 10.11 or with any FGFR fusion.
b. 
Adult subjects with any FGFR gene fusion are eligible for enrollment in the Broad Panel Cohort. FGFR gene fusions must have an intact
FGFR kinase domain. FGFR gene identifiers for reference are provided in Section 5.1, Criterion 2.
c. 
The Response-evaluable Population is composed of subjects who received at least 1 dose of study drug; met eligibility criteria for the
study; and had a baseline and at least 1 adequate post-treatment radiological disease evaluation, had clinical signs or symptoms of disease
progression, or died prior to the first posttreatment disease evaluation (these subjects will be considered non-responders). Adequate
disease assessment is defined as having enough evidence to indicate that disease progression has or has not occurred.
d. 
The Core Panel Cohort is a subgroup of the Broad Panel Cohort Treated Population composed of subjects with a specified subset of
core FGFR alterations listed in Section 9.3.1. This is an analysis cohort only.
e. 
Subjects with FGFR mutations not on the List of Target FGFR Mutations will be included in the Exploratory Cohort.
f. 
The Exploratory Cohort is closed for enrollment as of 11 May 2020.
g. 
A separate Cholangiocarcinoma Expansion Cohort will enroll subjects with target FGFR mutations or any FGFR gene fusion once the
Broad Panel Cohort has reached the cap of approximately 30 subjects for cholangiocarcinoma
h. 
The Pediatric Cohort will enroll 20 children or adolescent subjects who have progressed following prior therapies and who have no
acceptable standard therapies, and approximately 6 additional children or adolescent subjects who have a newly-diagnosed solid tumor
and who have no acceptable standard therapies. Adolescent subjects enrolled in the Broad Panel Cohort will be analyzed as part the
Broad Panel Cohort and the Pediatric Cohort.
i. 
FGFR gene amplifications or copy number variation (CNV) are not eligible. See Section 5.1 for molecular eligibility criteria definitions.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
38
Status: Approved, Date: 22 February 2023
A Data Review Committee (DRC) will be commissioned for this study. Refer to Committees
Structure in Section 10.3, Regulatory, Ethical, and Study Oversight Considerations for details.
4.2. 
Scientific Rationale for Study Design
4.2.1. 
Cohort Design
This study will enroll subjects into 4 cohorts (the Broad Panel Cohort, the Exploratory Cohort, the
Cholangiocarcinoma Expansion Cohort, and the Pediatric Cohort). The histology agnostic Broad
Panel Cohort will enroll subjects ≥12 years of age with target FGFR mutations or any FGFR gene
fusion. The Exploratory Cohort will enroll subjects with FGFR mutations not captured inthe Broad
Panel Cohort. A separate Cholangiocarcinoma Expansion Cohort will enroll subjects with target
FGFR mutations or any FGFR gene fusion once the Broad Panel Cohort has reached the cap of
approximately 30 subjects for cholangiocarcinoma. The definition of target FGFR mutations and
rationale for the cohort design are outlined below. The Pediatric Cohort will enroll subjects ≥6 to
<18 years of age with FGFR mutations, any FGFR gene fusion, or FGFR internal tandem
duplication. Adolescent subjects enrolled in the Broad Panel Cohort (≥12 to <18 years) will be
analyzed as part of the Broad Panel Cohort and the Pediatric Cohort.
Over 8,000 unique mutations in FGFR1-4 have been reported in the GENIE (the AACR Project
Genomics Evidence Neoplasia Information Exchange) and FoundationInsights™ genomic
databases as of February and May 2019, respectively. It is possible that many of these mutations
represent passenger events and may not be drivers of disease. To identify FGFR mutations with
oncogenic driver potential and sensitivity to erdafitinib, genomic filtering and in-vitro sensitivity
assays were applied to FGFR mutations in the GENIE and FoundationInsights databases.
The GENIE database represents ~46,000 patients across 48 cancers, and the FoundationInsights
database contains genomic data from ~231,000 patients from 64 cancers. The >8,000 unique
mutations in FGFR1-4 were collected and annotated for pathogenicity based on the following
criteria:
 Presence of the variant in 1 of 2 oncology variant knowledge databases, which annotate
the oncogenic effect of somatic molecular alterations (OncoKB 2019, Chakravarty 2017,
Cancer Hotspots 2019, Chang 2018)
 Annotation of the variant in Foundation Insights genomic database indicating known or
likely pathogenicity
 Variant recurrently detected in the GENIE genomic database (GENIE 2019)
 Variant 
recurrently 
detected 
in 
the 
FoundationInsights 
genomic 
database
(FoundationInsights 2019)
 Variant identified in multiple tumor types across genomic datasets
 Variant is not in a position of a canonical gatekeeper mutation (FGFR1_V561,
FGFR2_V564, FGFR2_N549; FGFR3_V555, FGFR4_V550)

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
39
Status: Approved, Date: 22 February 2023
The resulting list of FGFR mutations were subsequently tested in transient transfection assays for
in-vitro sensitivity to erdafitinib, determined by inhibition of extracellular-signal-regulated kinase
(ERK) phosphorylation. FGFR mutations meeting the above criteria and with in-vitro sensitivity
to erdafitinib were designated as target FGFR mutations. The list of Target FGFR Mutations also
includes additional mutations with clinical or correlative evidence supporting inclusion. The List
of Target FGFR Mutations is provided in Section 10.11.
The frequency of target FGFR alterations in Table 1 includes filtering for likely pathogenic FGFR
gene fusions based on assessment of fusion characteristics and recurrence. Molecular eligibility
for this study has been extended to subjects with any FGFR gene fusion (FGFR gene fusions must
have an intact FGFR kinase domain. FGFR gene identifiers for reference are provided in
Section 5.1 Criterion 2). This extension of molecular ability is based on clinical experience in
cholangiocarcinoma and other tumor types where clinical responses to erdafitinib were observed
in patients with novel gene fusions.
A subgroup of subjects in the Broad Panel Cohort with a defined panel of pre-specified FGFR
markers will be identified as the Core Panel Cohort (see Section 9.3.1). The Core Panel Cohort
will be used only for statistical analysis purposes and will not affect enrollment. FGFR markers
for the Core Panel Cohort were selected based on observed clinical activity in previous studies or
a high level of recurrence of these alterations across tumor histologies.
The selection process described above, while aiming to increase the likelihood of evaluating
erdafitinib activity in FGFR-driven tumors, is not expected to capture all FGFR mutations with
oncogenic driver potential or sensitivity to erdafitinib. Therefore, the Exploratory Cohort has been
included to capture and assess driver mutation potential and sensitivity in FGFR mutations not
eligible for the Broad Panel Cohort.
Subjects from all solid tumor histologies (except bladder) with an FGFR mutation or fusion
identified via local testing results (as outlined in Section 8.1.1.1) are considered molecularly
eligible for the study, pending review and approval by the sponsor. However central molecular
screening will be selective to specified tumor histologies. Based on the predicted frequency of
target FGFR alterations, prevalence of tumor histology, and predictive modeling of distribution;
the tumor histologies that were selected for central molecular screening in this study are provided
in Figure 6.
4.2.2. 
Biomarker Collection
Biomarker samples will be collected to evaluate the mechanism of action of erdafitinib and may
help to identify population subgroups that respond differently to erdafitinib. The goal of the
biomarker analyses is to further understand the mechanism of action and potential
erdafitinib-clinical response relationships. Biomarker samples may be used to help address
emerging issues and to enable the development of safer, more effective, and ultimately
individualized therapies.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
40
Status: Approved, Date: 22 February 2023
4.2.3. 
Patient-reported Outcomes Research
Patient-reported outcome data complement data collected by other methods to support the clinical
data and cost-effectiveness modeling as well as contributing to enhanced communication of value
to patients, clinicians, regulators, and payers. The patient-reported outcome (PRO) endpoints of
interest include domain scales from the EORTC-QLQ-C30 (for subjects ≥18 years of age) or Peds
FACT-Br (for subjects <18 years of age), PGIS, PGIC, and EQ-5D-5L (utility value and visual
analog scale). PRO assessments are necessary to quantify patient benefit early in the development
on an investigational drug. Collecting PRO assessments at this time will support further
development in future studies. PRO data will be collected as outlined in the Schedule of Activities
to understand how the endpoints change over time.
4.2.4. 
Study-Specific Ethical Design Considerations
Potential subjects will be fully informed of the risks and requirements of the study and, during the
study, subjects will be given any new information that may affect their decision to continue
participation. They will be told that their consent to participate in the study is voluntary and may be
withdrawn at any time with no reason given and without penalty or loss of benefits to which they
would otherwise be entitled. Only subjects (or their legally acceptable representative) who are fully
able to understand the risks, benefits, and potential adverse events of the study, and provide their
consent voluntarily will be enrolled.
When referring to the signing of the informed consent/assent form (ICF), the terms legal guardian
and legally acceptable representative refer to the legally appointed guardian of the child with
authority to authorize participation in research. For each subject, his or her parent(s) (preferably both
parents, if available) or legally acceptable representative(s), as required by local regulations, must
give written consent (permission) according to local requirements after the nature of the study has
been fully explained and before the performance of any study-related assessments. Assent must be
obtained from children (minors) capable of understanding the nature of the study, typically subjects
7 years of age and older, depending on the institutional policies; children ≥6 to <12 years of age,
adolescents 12 years of age and above and adults will be enrolled in this study. Minors who reach
the age of majority (per local regulations) during study will need to (re)sign an ICF. For the purposes
of this study, all references to subjects who have provided consent (and assent as applicable) refers
to the subjects and his or her parent(s) or the subject's legal guardian(s) or legally acceptable
representative(s) who have provided consent according to this process. Minors who assent to a study
and later withdraw that assent should not be maintained in the study against their will, even if their
parent(s) still want them to participate.
In view of the positive results for the subjects with urothelial cancer and select FGFR alterations
in these studies and the prognosis for the subject population being considered for the study, a
positive risk-benefit profile is anticipated. It should be noted that in the Phase 1 study, different
histologies harboring FGFR amplifications, mutations or translocations did not behave uniformly
to erdafitinib treatment. Instead the response was higher in certain tumor histologies such as
urothelial cancer or cholangiocarcinoma compared to other tumor histologies included in the study.
Subjects will be closely monitored throughout the study, as discussed throughout this protocol, for

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
41
Status: Approved, Date: 22 February 2023
both safety and clinical benefit.
The potential risks of erdafitinib to adults, as well as children and adolescents, include central
serous retinopathy and hyperphosphatemia. Pre-clinical findings of cartilage dysplasia could be
indicative of possible bone growth abnormalities in children and adolescents. The safety profile of
erdafitinib, based on the urothelial population, was characterized by mild to moderate eye, skin
and nail disorders; these events were manageable with available medical measures, temporary
treatment interruption, or eventual dose reduction.
The total blood volume (approximately 230 mL for adults and 275 mL for adolescents over
6 cycles, including the screening and end of study visits [approximately 15 mL is collected at each
additional cycle]) that will be collected is considered within the normal range allowed for this
subject population over this time frame, including the adolescent subjects. For adult subjects, the
amount of blood collected is less than the American Red Cross standard blood donation of 500 mL
over 60 days (American Red Cross 2019). For children and adolescents, generally no more than
1 percent of the total blood volume may be collected at any one draw or over a 24-hour period,
and no more than 3 percent of the total blood volume may be collected over a 30-day period
(Veal 2014, Howie 2011, EMA 2019). Thus, an adolescent weighing 40 kg would have a total
blood volume of 3.2 liters and a limit of approximately 30 mL at any 1 blood draw and 90 mL over
30 days. In this study, the total blood volume collected from an adolescent subject weighing 40 kg
exceeds the 30 mL limit at Cycle 1 Day 1 visit only, due to the collection of a 20 mL blood sample
for circulating tumor DNA. All subsequent study visits do not collect blood volumes in excess of
30 mL. This difference from the maximum limit increases as body weight decreases. The
investigator should evaluate the risk versus the potential benefit of enrolling an adolescent subject
with lower body weights into this study.
4.2.5. 
Participant Input Into Design
The results of the study may be made available to all participants through a plain language
summary; a technical summary of results on registries such as clinicaltrials.gov,
clinicaltrialsregister.eu or other national registries at the conclusion of the study according to local
standards/restrictions.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
42
Status: Approved, Date: 22 February 2023
4.3. 
Justification for Dose
Adult Dose Justification
In adults, erdafitinib will be provided as a tablet for oral administration and subjects will be
instructed to take an 8-mg starting dose orally once daily on a continuous 21-day cycle, until
disease progression, intolerable toxicity, withdrawal of consent, decision by the investigator to
discontinue treatment, or the end of data collection timepoint has been achieved. Treatment will
be up-titrated to 9 mg, maintained at 8 mg, or withheld; based on the phosphate level measured on
Cycle 1 Day 14 and the observed toxicity to that day, as described in detail in Section 6.1.
The 8-mg starting dose was selected based on PD biomarker (serum phosphate), clinical activity,
and safety data as summarized below.
Clinical Activity
Data from the completed Phase 1 Study EDI1001 indicates that an increase in phosphate level of
at least 35% over the baseline level may be associated with anti-tumor response. Therefore, a PD
objective of a 50% increase in phosphate level over baseline is considered clinically meaningful.
Given the median phosphate level of 3.6 mg/dL at baseline in the Phase 1 study, and the phosphate
level of 3.3 mg/dL at baseline in the Phase 2 Study BLC2001 (Interim Analysis 1 data), an increase
of at least 50% for the majority of subjects would correspond to an absolute phosphate level of
around 5.5 mg/dL (which is also 35% over the upper limit of normal for phosphate). Subjects
achieving a phosphate level of less than 5.5 mg/dL during the first dosing cycle period would be
considered to have had inadequate PD effect and would be candidates for dose escalation or
up-titration to the 9-mg once daily dose to achieve an optimal PD effect (ie, phosphate level above
5.5 mg/dL).
In Study BLC2001, analysis of clinical response for all subjects in the 8-mg daily regimen shows
that while responses were achieved both above and below 5.5 mg/dL, the ORR and DCR were
higher (43.1% vs. 34.6% for ORR; 86.1% vs. 65.4% for DCR), and DOR and PFS were longer
(6.01 vs. 4.44 months for DOR; 5.59 vs. 3.81 months for PFS) in subjects with a serum phosphate
level ≥5.5 mg/dL compared to those with a level <5.5 mg/dL (BLC2001). Of note, all 3 CRs
occurred in subjects with serum phosphate ≥5.5 mg/dL. Median OS for subjects with serum
phosphate ≥5.5 mg/dL was not reached with a lower bound of the 95% confidence interval (CI) at
11.3 months, while median OS was 7.49 months for subjects with serum phosphate less than
5.5 mg/dL (BLC2001).
Based on an exploratory analysis of response for subjects in the 8-mg daily regimen in Study
BLC2001, when a higher phosphate level of 7 mg/dL was used as the new threshold, a larger
separation of clinical response was observed between subjects with serum phosphate ≥7 mg/dL
and <7 mg/dL (45.5 vs. 31.6% for ORR; 90.9% vs. 75% for DCR).
Hence, the clinical goal is to maximize the number of subjects reaching the new target phosphate
level of 7 mg/dL in order to attain maximum and sustained target inhibition.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
43
Status: Approved, Date: 22 February 2023
Clinical Safety
The 8-mg daily regimen from the ongoing Study BLC2001 was well tolerated and without
significant treatment interruptions (approximately 10% to 15% anticipated early interruptions).
Up-titration from the 8-mg daily regimen to the 9-mg daily regimen on Cycle 1 Day 14 in subjects
with both serum phosphate level below 5.5 mg/dL (ie, suboptimal PD effect) and without
significant drug-related toxicity (ie, Grade ≥2 toxicity or Grade ≥1 central serous retinopathy or
retinal pigment epithelial detachments) is likely to have a good overall tolerability profile and
increases the likelihood of improved efficacy.
Moreover, the observed safety of the 9-mg daily regimen in the completed Phase 1 Study EDI1001
did not raise concerns about prolonged hyperphosphatemia, and no soft-tissue calcification or
electrolyte disturbance or endocrine abnormalities were reported. Similarly, in the ongoing Phase 2
study, no such abnormalities were observed. Therefore, a more aggressive approach to up-titration
may be adopted, allowing up-titration in subjects whose Day 14 phosphate is below 7 mg/dL
(instead of below 5.5 mg/dL) without concurrent temporary use of phosphate binder treatment, or
whose serum phosphate is between 7 and 9 mg/dL with concurrent temporary use of phosphate
binder treatment (see Section 6.1).
In conclusion, the pharmacodynamically-guided dose up-titration scheme from 8-mg daily
regimen to 9-mg daily regimen based on the target phosphate level of 7 mg/dL on Cycle 1 Day 14
is expected to increase clinical activity without significantly increasing dose interruptions or
toxicity. The appropriateness of this proposed dosing regimen is also supported by modeling and
simulations and is currently being tested in Phase 3 study BLC3001 and subsequent erdafitinib
studies, ie, the proposed up-titration scheme is predicted to achieve serum phosphate target level
of 7 to 9 mg/dL in more subjects compared to the reference up-titration scheme using target
phosphate level of 5.5 mg/dL, while not increasing the number of unforeseen dose interruptions
and dose adaptations.
Children and Adolescent Dose Justification
For adolescents aged ≥15 years to <18 years, the adult regimen of 8 mg once daily with up-titration
to 9 mg once daily on Cycle 1 Day 14 will be used. For adolescents aged ≥12 years to <15 years
(ie, until the day before they turn 15 years of age), the 5-mg daily starting dose with possible
up-titration to 6 mg daily or further up-titration to 8 mg (maximum) daily will be used. For children
aged ≥6 to <12 years (ie, until the day before they turn 12 years of age), the 3 mg daily starting
dose with possible up-titration to 4 mg daily or further up-titration to 5 mg (maximum) daily will
be used. The up-titration decision for adolescents 12 to <15 of age and children ≥6 to <12 years of
age will be based on the phosphate level measured on Cycle 1 Day 14 and Cycle 2 Day 7 and the
observed toxicity to that day, as described in detail in Section 6.1. Specifically, the up-titration
scheme is an age group dependent 2-step approach. No subjects will be allowed to up-titrate
directly from the starting dose of 3 mg and 5 mg to the maximum daily dose of 5 mg and 8 mg for
children aged ≥6 to <12 years and adolescents ≥12 to <15 years of age, respectively. The
adolescent (≥12 to <15 years of age) and children (≥6 to <12 years of age) dose selections are

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
44
Status: Approved, Date: 22 February 2023
primarily driven by the baseline serum phosphate level and age effect on phosphate. The weight
effect on pharmacokinetics is minimal relative to the age effect on phosphate. No new safety
signals were observed following a review of data by the DRC from the first 2 adolescent subjects
(12 and 13 years of age) enrolled in the Broad Panel Cohort.
It has previously been shown that serum phosphate is a biomarker for erdafitinib’s safety and
efficacy based on the BLC2001 Study. In addition, it is known that serum phosphate is highly
correlated with age. Based on erdafitinib studies, adults have an average serum phosphate baseline
level of 3.1 mg/dL for men and 3.5 mg/dL for women. However, among adolescents across the
age range of 11 to 15 years, it has been reported that the median serum phosphate level is
4.9 mg/dL and 4.5 mg/dL in boys and girls, respectively and for children across the age range of
6 to 10 years 5.0 mg/dL (Adeli 2015). The serum phosphate level shows a trend of higher values
among children and younger adolescents and a gradual decrease to the adult value among older
adolescents.
Using the established PK-PD model, assuming similarity in the PK-PD relationship between
adults, adolescents and children, higher phosphate baseline distribution in adolescents and children
compared to adults and similar target phosphate threshold (7-9 mg/dL) between adults, adolescents
and children; simulations were conducted across the different age groups (≥6 to <12, ≥12 to <15,
and ≥15 to <18) to predict the percentage of subjects reaching the target phosphate range and safety
phosphate threshold (>9 mg/dL). The appropriate dosing regimen of children and adolescents was
selected for different age groups based on i) maximizing the proportions within the target
phosphate range, ii) minimizing the proportions above the target phosphate range, and
iii) minimizing the proportions with treatment interruptions as predicted by the PK-PD model, as
well as clinical considerations.
Among adolescents aged ≥15 to <18 years of age following the adult regimen, at week 6, which
corresponds to the median time to response and time of peak serum phosphate level, the percentage
of subjects within the target phosphate range was predicted to be 30.2%, compared to 21.6% in
adults. The percentage of subjects ≥15 to <18 years of age above the safety threshold was predicted
to be 11.7% compared to 6.9% in adults, and 20.4% of subjects were predicted to have their dose
interrupted within the first 6 weeks compared to 13% in adults. These predictions suggest that
among this older group of adolescents, following the same dosing regimen as adults is likely to be
acceptable from both safety and efficacy perspectives.
Among adolescents aged ≥12 to <15 years of age, the adult regimen leads, on average, to 20.4%
subjects above the target phosphate range, which is more than the 13.8% pre-specified 2-fold
increase compared with the adult reference and was not deemed acceptable. A lower starting dose
of 5 mg with up-titration to 6 mg and a starting dose of 6 mg with up-titration to 8 mg led to an
acceptable proportion of subjects with phosphate levels above 9 mg/dL, while retaining a good
proportion of subjects within the target phosphate range. The dosing algorithm was further refined
to allow for 2 possible up-titrations. This would allow younger adolescents to potentially benefit
from a wider spread of doses, between 5 and 8 mg. Up-titrations at Day 7 and 14 and up-titrations
at Day 14 and 28 were tested. The proportion of adolescents within and above the target phosphate

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
45
Status: Approved, Date: 22 February 2023
range after refinement led to 39.5% of subjects within the target range, while maintaining the
proportion below 13.8% for the 2-week up-titration (14.8% for the 1-week up-titration and 12.0%
for the 2-week up-titration). The proportion of subjects whose dose was interrupted was predicted
27.8% and 24.7% for the 1- and 2-week scenario, respectively. As the 2-week interval allows PK
and PD to reach steady-state and leads to satisfactory efficacy and safety proportions, a 5-6-8 mg
dose regimen with up-titrations at Day 14 and Day 28 was selected as the recommended dose for
adolescents ≥12 to <15 years old. Note that the predicted proportion of up-titrated subjects is
around 96% at Day 14 and 85% at Day 28 for the selected scenario with starting dose of 5 mg and
2-week up-titration to 6 and 8 mg.
Given the results in young adolescents, simulations for children ≥6 to <12 years focused on
2 up-titrations either 1 week or 2 weeks apart. The regimen that was deemed to best match the
adult reference was a starting dose of 3 mg with 4 and 5 mg up-titrations at 2-weekly intervals, ie,
at Day 14 and Day 28 with 42.8% of subjects within the target range while maintaining the
proportion above the target range at 9.9%. The proportion of subjects whose dose was interrupted
was predicted to be 22.3%. Note that the predicted proportion of subjects up-titrated is around 96%
at Day 14 and 87% at Day 28.
The table below shows an overview of proposed pediatric dosing regimens maximizing the
proportion of children and adolescent subjects within the target range, while keeping the
proportion of children and adolescent subjects that require interruptions due to phosphate levels
>9 mg/dL, less than or equal to 12%.
Age group  
Proposed erdafitinib dose regimen
Adults (reference) 
8 mg with potential up-titration to 9 mg on Day 14
Adolescents ≥15 to <18 years 8 mg with potential up-titration to 9 mg on Day 14 (same as adult dose)
Adolescents ≥12 to <15 years 5 mg with potential up-titration to 6 mg on Day 14 and 8 mg on Day 28
Children ≥6 to <12 years 
3 mg with potential up-titration to 4 mg on Day 14 and 5 mg on Day 28
As it is unknown whether the sensitivity to erdafitinib as well as the phosphate thresholds observed
in adults directly translate to children and adolescents, the simulation results need to be interpreted
with caution. However, if elevated phosphate levels are observed in children or adolescents during
the study, the phosphate elevation management guideline as described in Table 3 (Erdafitinib Dose
Modification Rules Based on Toxicity Severity) and Table 8 (Guidelines for Management of
Serum Phosphate Elevation) will be followed. In addition, this protocol mandates additional PK
sampling and serum phosphate testing on blood samples collected on Cycle 1 Day 14 and Cycle 2
Day 14 for children and adolescents. Emerging PK and phosphate data, as well as efficacy and
safety data, will be analyzed after a minimum of 5 children and adolescent subjects become
evaluable for response, and used for PK-PD analysis to evaluate the need for modification of the
dosing regimen in adolescents.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
46
Status: Approved, Date: 22 February 2023
5. 
STUDY POPULATION
Screening for molecular eligibility is performed prior to the Full-study Screening Period. See
information on the consent process for molecular screening in Section 8.1.1. Full study screening
for molecularly eligible subjects will be performed within 30 days before administration of the
study drug.
The inclusion and exclusion criteria for enrolling subjects in this study are described below. If
there is a question about these criteria, the investigator must consult with the appropriate sponsor
representative and resolve any issues before enrolling a subject in the study. Waivers are not
allowed.
For a discussion of the statistical considerations of subject selection, refer to Section 9.2, Sample
Size Determination.
5.1. 
Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study:
1. 
Criterion modified per Amendment 3
1.1 ≥6 years of age.
2. 
Criterion modified per Amendment 1
2.1 Criterion modified per Amendment 2
2.2 Criterion modified per Amendment 3
2.3 Histologic demonstration of an unresectable, locally advanced, or metastatic solid
tumor malignancy bearing an FGFR mutation or fusion, as determined by local* or
central laboratory screening (Section 8.1.1.1).
* Locally performed or commercial testing results from tissue or blood with NGS tests,
direct digital counting methods, or the Qiagen therascreen® FGFR RT-PCR test
performed in Clinical Laboratory Improvement Amendments (CLIA)-certified or
regional equivalent laboratories.
Molecular Criteria for Broad Panel Cohort and Cholangiocarcinoma Expansion Cohort:
 
Subjects with target FGFR mutations or any** FGFR gene fusions are eligible for
enrollment in the Broad Panel Cohort (The List of Target FGFR Mutations is
provided in Section 10.11).
 
Subjects with other FGFR mutations*** not captured in the Broad Panel Cohort are
eligible for enrollment in the Exploratory Cohort.
Molecular Criteria for Pediatric Cohort:
 
Subjects with any FGFR mutation*** (exclusive of FGFR valine gatekeeper and
resistance alterations defined in the Exclusion Criteria) or any** FGFR gene fusions,

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
47
Status: Approved, Date: 22 February 2023
or FGFR internal tandem duplication**** are eligible for enrollment in the Pediatric
Cohort
**FGFR Fusion Specifications:
 
Have a report suggesting the presence of an intact FGFR kinase domain
 
FGFR fusion with a 3-prime partner (FGFR gene is listed first, eg FGFR-GENE or
FGFR3-TACC3):
 
The FGFR portion of the fusion must involve exon 17 or greater (≥17)
 
FGFR fusion with a 5-prime partner (Partner gene is listed first and FGFR gene is
second, eg GENE-FGFR or KLK2-FGFR2):
 
The FGFR portion of the fusion must involve less than or equal to exon 11 (≤11)
 
Have a named FGFR fusion partner gene (self-fusions or rearrangements, eg FGFR-
FGFR, are not eligible) (Broad Panel Cohort only)
FGFR gene identifiers, canonical transcript identifiers, and kinase domain positions are
provided below for reference.
Gene 
Ensembl ID  
RefSeqID  
mRNA  
Kinase 
Domain AA 
Positionⱡ 
Kinase
Domain
Exonsⱡ
FGFR1 
ENST00000447712 
NM_023110.3 
478 → 754  
Exons 11-17
FGFR2 
ENST00000358487 
NM_000141.5 
481 → 757 
Exons 11-17
FGFR3 
ENST00000440486 
NM 000142.4 
478 → 754  
Exons 11-17
FGFR4 
ENST00000292408 
NM_002011.5 
467 → 743 
Exons 11-17
Pfam=Protein Families (database)
Kinase domains defined by Pfam annotations from NCBI Entrez Gene. Exons of the RefSeq
transcript are inclusive of the kinase domain. Exon boundaries defining the kinase domain are
equivalent to NM_015850.
*** Mutations in this study are defined as protein-coding single nucleotide variant
(SNV) and insertions or deletions (indels). Copy number gains or gene-level
amplifications are not eligible. FGFR mutations annotated as germline in local reports,
or subjects presenting with a hereditary condition/disorder associated with a germline
FGFR mutation are not eligible for enrollment in the absence of a qualifying FGFR
mutation or fusion. Note, testing for germline mutations is not required for this study.
**** For Pediatric Cohort Only: Intragenic duplication of the FGFR kinase domain
(FGFR-FGFR) if one breakpoint is located within intron 8 through exon 11 and the
other breakpoint is in intron 17 through intron 18 (including 3' UTR). Copy number
gains or gene-level amplifications are not eligible.
3 
Measurable disease according to RECIST v1.1 or RANO for primary brain tumors.
4. 
Criterion modified per Amendment 2
4.1 Criterion modified per Amendment 3

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
48
Status: Approved, Date: 22 February 2023
4.2 Subject must have received at least one prior line of systemic therapy in the
advanced, unresectable, or metastatic setting; or is a child or adolescent subject with a
newly-diagnosed solid tumor and no acceptable standard therapies.
5. 
Subject does not have standard of care options that have shown meaningful clinical
benefit for the relevant underlying histology and line of therapy or the subject is unable
to tolerate the therapy.
6. 
Criterion modified per Amendment 4
6.1 Documented progression of disease, defined as any progression that requires a
change in treatment, prior to full study screening. Note: Not applicable for treatment
naïve pediatric subjects with no standard of care therapies.
7. 
Toxicities from previous anticancer therapies should have resolved to baseline levels or
to Grade 1 or less except for alopecia, peripheral neuropathy, and Grade 2 laboratory
values eligible per Inclusion Criterion 9.
8. 
Criterion modified per Amendment 3
8.1 Criterion modified per Amendment 4
8.2 For adults (≥18 years of age), ECOG performance status Grade 0 or 1
(Section 10.5).
For children and adolescents (≥6 to <16 years of age), Lansky Score of ≥70
(Section 10.6).
For adolescents (≥16 to <18 years of age), Karnofsky Score of ≥70 (Section 10.6).
9. 
Criterion modified per Amendment 1
9.1 Criterion modified per Amendment 2
9.2 Criterion modified per Amendment 3
9.3 Adequate bone marrow, liver, and renal function:
a. Bone marrow function (without the support of cytokines or erythropoiesis-stimulating
agent transfusions in preceding 2 weeks):
 
Absolute neutrophil count (ANC) ≥1,000/mm3
 
Platelet count ≥75,000/mm3
 
Hemoglobin ≥8.0 g/dL
b. Liver function:
 
Total bilirubin ≤1.5 x institutional ULN OR direct bilirubin ≤ULN for subjects
with total bilirubin levels >1.5xULN
 
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5x
institutional ULN or ≤5x institutional ULN for subjects with liver metastases

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
49
Status: Approved, Date: 22 February 2023
c. Renal function: Creatinine clearance (CrCl) >30 mL/min calculated using the
Cockcroft-Gault formula for adult subjects or the CKiD (Chronic Kidney Disease in
Children) Schwartz formula for children and adolescent subjects (≥6 to <18 years of
age) (Section 10.7)
d. Phosphate: <ULN within 14 days of treatment and prior to Cycle 1 Day 1 (medical
management allowed)
10. 
Criterion modified per Amendment 3
10.1 Must sign an ICF (or their legally acceptable representative must sign) indicating
that the subject understands the nature, significance, and purpose of the study, and
procedures required for the study, and consequence of the study; and is willing to
participate in the study. For children and adolescent subjects, parent(s) (preferably both if
available or as per local requirements) (or their legally acceptable representative) must
sign an ICF indicating that the subject understands the purpose of, and procedures
required for, the study and is willing to allow the child to participate in the study. Assent
is also required of children and adolescent subjects as described in Informed Consent
Process in Section 10.3, Regulatory, Ethical, and Study Oversight Considerations.
11. 
A female of childbearing potential must have a negative pregnancy test (β-human
chorionic gonadotropin [hCG]) at Screening (urine or serum).
12. 
Criterion modified per Amendment 1
12.1. Criterion modified per Amendment 3
12.2. Contraceptive use by male or female subjects should be consistent with local
regulations regarding the use of contraceptive methods for subject participating in
clinical studies.
For females of childbearing potential (defined as: fertile, following menarche and until
becoming post-menopausal unless permanently sterile [for the purpose of this study].
Permanent sterilization methods include hysterectomy, bilateral salpingectomy and
bilateral oophorectomy):
 
practice a highly effective method of contraception (failure rate of <1% per year
when used consistently and correctly)
Examples of highly effective contraceptives include
 
user-independent methods: implantable progestogen-only hormone
contraception associated with inhibition of ovulation; intrauterine device
(IUD); intrauterine hormone-releasing system (IUS); vasectomized partner;
permanently sterile; sexual abstinence: true abstinence when this is in line with
the preferred and usual lifestyle of the subject (Note: periodic abstinence [eg,
calendar, ovulation, symptothermal, post-ovulation methods], declaration of

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
50
Status: Approved, Date: 22 February 2023
abstinence for the duration of exposure to study drug, and withdrawal are not
acceptable methods of contraception.)
 
user-dependent methods: combined (estrogen- and progestogen-containing)
hormonal contraception associated with inhibition of ovulation: oral,
intravaginal, and transdermal; progestogen-only hormone contraception
associated with inhibition of ovulation: oral and injectable
 
agree to remain on a highly effective method of contraception during the study and
for at least 3 months after the last dose of study drug
 
agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction
during the study and for at least 3 months after the last dose of study drug
 
no plan to breastfeed and no plan to become pregnant during the study and for at
least 3 months after the last dose of study drug
For males who are sexually active:
 
agree to use a condom with spermicidal foam/gel/film/cream/suppository
 
agree to not donate sperm during the study and for at least 3 months after the last
dose of study drug
 
no plan to father a child during the study or within 3 months after the last dose of
study drug
5.2. 
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating
in the study:
1. 
Criterion modified per Amendment 2
1.1 Criterion modified per Amendment 3
1.2 Has had prior chemotherapy, targeted therapy, or treatment with an investigational
anticancer agent within 15 days or <5 half-lives of the agent (whichever is longer) and
up to a maximum of 30 days before the first dose of erdafitinib. Has had prior
monoclonal antibody or immunotherapy within 30 days before the first dose of
erdafitinib and/or has an ongoing Grade ≥2 immunotherapy-related toxicity.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
51
Status: Approved, Date: 22 February 2023
2. 
Criterion modified per Amendment 2
2.1 Criterion modified per Amendment 3
2.2 The known* presence of FGFR valine gatekeeper and resistance alterations.
Mutations in the following positions: FGFR1 V561; FGFR2 V564; FGFR3 V555;
FGFR4 V550; FGFR1 N546; FGFR2 N549; FGFR3 N540 and FGFR4 N535.
* Observation of a gatekeeper/resistance alteration in the local or central report. If the
local test does not screen for all four FGFRs, eg FGFR4, the local report remains
evaluable for molecular screening.
3. 
Criterion modified per Amendment 1
3.1 Criterion modified per Amendment 2
3.2 Criterion modified per Amendment 3
3.3 Criterion modified per Amendment 4
3.4 For NSCLC subjects only - pathogenic somatic mutations in EGFR* or BRAF
V600E, KRAS, or any gene fusions in the following genes: ALK, ROS1, or NTRK.
* Assessment of these genes may be performed per institutional standard and do not
have to be assessed via NGS.
For colorectal subjects only –pathogenic somatic mutations in BRAF, KRAS, NRAS
and PIK3CA.
4. 
Criterion modified per Amendment 2
4.1 Histologic demonstration of urothelial carcinoma.
5. 
Hematologic malignancy (ie, myeloid and lymphoid neoplasms).
6. 
Active malignancies other than for disease requiring therapy.
7. 
Symptomatic central nervous system metastases (except for subjects with primary CNS
tumors).
8. 
Criterion modified per Amendment 2
8.1 Received prior selective FGFR inhibitor treatment.
9. 
Known allergies, hypersensitivity, or intolerance to erdafitinib or its excipients.
10. 
Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of
any grade.
11. 
Criterion modified per Amendment 1
11.1 Criterion modified per Amendment 2
11.2 Criterion modified per Amendment 3

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
52
Status: Approved, Date: 22 February 2023
11.3 History of uncontrolled cardiovascular disease including:
 
Unstable angina, myocardial infarction, ventricular fibrillation, Torsades de
Pointes, cardiac arrest, or known congestive heart failure Class III-IV
(Section 10.8) within the preceding 3 months; cerebrovascular accident or transient
ischemic attack within the preceding 3 months.
 
QTc prolongation (Fridericia: QTc >480 milliseconds; or for children and
adolescent subjects, Bazett: QTc >440 milliseconds).
12. 
Known history of AIDS (human immunodeficiency virus [HIV] infection), unless the
subject has been on a stable anti-retroviral therapy regimen for the last 6 months or
more, has had no opportunistic infections in the last 6 months, and has CD4 count >350
13. 
Criterion modified per Amendment 1
13.1 Criterion modified per Amendment 2
13.2. Evidence of active hepatitis B or C infection (for example, subjects with history
of hepatitis C infection but normal hepatitis C virus polymerase chain reaction [PCR]
test and subjects with inactive hepatitis B with positive HBsAg antibody or normal PCR
are allowed).
14. 
Not recovered from reversible toxicity of prior anticancer therapy (except toxicities
which are not clinically significant such as alopecia, skin discoloration, neuropathy,
hearing loss).
15. 
Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers,
known gastric ulcers, or unhealed incisions.
16. 
Major surgery within 4 weeks before first dose of erdafitinib.
17. 
Criterion modified per Amendment 2
17.1 Palliative radiation to the target lesion within 2 weeks before the first dose of
erdafitinib.
18. 
Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study
or within 3 months after the last dose of drug.
19. 
Plans to father a child while enrolled in this study or within 3 months after the last dose
of drug.
20. 
Any condition for which, in the opinion of the investigator, participation would not be
in the best interest of the subject (eg, compromise the well-being) or that could prevent,
limit, or confound the protocol-specified assessments. Examples include ongoing active
infection requiring systemic therapy and uncontrolled ongoing medical conditions.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
53
Status: Approved, Date: 22 February 2023
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening.
If a subject's clinical status changes (including any available laboratory results or receipt of
additional medical records) after screening but before the first dose of study drug is given such
that the subject no longer meets all eligibility criteria, then the subject should be excluded from
participation in the study. The required source documentation to support meeting the enrollment
criteria is noted in Section 10.3, Regulatory, Ethical, and Study Oversight Considerations.
5.3. 
Lifestyle Considerations
Potential subjects must be willing and able to adhere to the following lifestyle restrictions during
the course of the study to be eligible for participation:
1. 
Refer to Section 6.5, Concomitant Therapies, for details regarding prohibited and
restricted therapy during the study.
2. 
Subjects should avoid consuming grapefruit or Seville oranges due to CYP 3A4/5
inhibition.
3. 
Subjects should check with the site prior to taking over the counter medication: known
to increase serum levels of phosphate, such as potassium phosphate supplements (oral
or IV), vitamin D supplements, antacids, and phosphate-containing enemas and
laxatives (oral/rectal) thought to increase serum phosphate levels.
4. 
Agree to follow all requirements that must be met during the study as noted in the
Inclusion and Exclusion Criteria (eg, contraceptive requirements).
5. 
Subjects should be advised on sperm banking and egg preservation, respectively, prior
to entering the study, if appropriate.
5.4. 
Screen Failures
Subject Identification, Enrollment, and Screening Logs
The investigator agrees to complete a subject identification and enrollment log to permit easy
identification of each subject during and after the study. This document will be reviewed by the
sponsor study-site contact for completeness.
The subject identification and enrollment log will be treated as confidential and will be filed by
the investigator in the study file. To ensure subject confidentiality, no copy will be made. All
reports and communications relating to the study will identify subjects by subject identification
and age at initial informed consent. In cases where the subject is not enrolled into the study, the
date seen and age at initial informed consent will be used.
Individuals who do not meet the criteria for participation in this study (screen failure) may be
rescreened only once for eligibility (Section 8.1.1).

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
54
Status: Approved, Date: 22 February 2023
5.5. 
Study Completion (ie, End of Data Collection Timepoint) and End of Study
5.5.1. 
Study Completion (ie, End of Data Collection Timepoint) Definition
The study is considered completed at the time of the end ofdata collection timepoint. Overall, the
end of data collection timepoint is defined as the date at which the clinical cutoff for the primary
analysis has been achieved. Specifically, for subjects <18 years of age, the end of data collection
is defined as the timepoint when the most recently enrolled pediatric subject still participating in
the study has 6 months of follow-up  or the last follow-up visit of the last pediatric subject,
whichever occurs first. Once the end of data collection timepoint has been achieved, follow-up of
subjects will end, and data collection will conclude. Only serious adverse events will be reported
in the company safety repository (See Appendix 13). The end of data collection timepoint may be
extended by the Sponsor, if needed, based on health authority feedback.
Subjects in the Treatment Phase who are continuing to derive benefit from study treatment as
determined by their investigator may continue to receive access to study treatment; during this
period, only serious adverse events will be reported into the company safety repository. Section 6.7
provides details on access to study drug after the End of Data Collection timepoint is achieved.
5.5.2. 
End of Study Definition –Overall Study
The end of study is considered as the time when the last subject receives the last dose of study
drug on the study and either all pediatric subjects are off study or until the most recently enrolled
pediatric subject still participating in the study has 6 months of follow-up, whichever occurs first.
6. 
STUDY DRUG
6.1. 
Study Drug Administered
Erdafitinib will be provided as tablets for oral administration. Subjects will be instructed to take
erdafitinib orally once daily for 21 days in a continuous 21-day cycle until disease progression,
intolerable toxicity, withdrawal of consent decision by the investigator to discontinue treatment.
For continued treatment with erdafitinib after the end of data collection timepoint has been
achieved see Section 6.7. Subjects or their parent/guardian will record study drug administration
in dosing diaries. Adults (aged 18 years and older) and adolescents aged ≥15 to <18 years will start
with a dose of 8 mg and the dose will be up-titrated to 9 mg or maintained at 8 mg based on Cycle
1 Day 14 serum phosphate levels. Adolescent subjects aged ≥12 to <15 years will start with an
erdafitinib dose of 5 mg with possible up-titration to 6 mg or further to 8 mg based on Cycle 1 Day
14 and Cycle 2 Day 7 serum phosphate levels. Children aged ≥6 to <12 years of age will start with
an erdafitinib dose of 3 mg with possible up-titration to 4 mg or further to 5 mg based on Cycle 1
Day 14 and Cycle 2 Day 7 serum phosphate levels. (See Section 4.3 for information on dose
justification.) Note that children and adolescent subjects will continue under the titration and
dosing schedule under which they were enrolled. Each dose should be taken at approximately the
same time each day, with or without food. The study drug is to be taken with approximately
240 mL (8 ounces) of water. The tablets should be swallowed intact. If the subject has difficulties
swallowing the tablets, tablets may be dispersed in apple juice or water, and administered via an
oral syringe. Alternatively, if the subject has difficulties swallowing the tablets or the tablet

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
55
Status: Approved, Date: 22 February 2023
dispersion via an oral syringe, tablets may be dispersed in water and administered via a feeding
tube. Refer to the pharmacy manual/study site Investigational Product Manual and the
Investigational Product Preparation Instructions for additional guidance on study drug preparation,
handling and storage. Subjects should avoid consuming grapefruit or Seville oranges due to CYP
3A4/5 inhibition. Study drug administration must be captured in the source documents and the
case report form (CRF). Erdafitinib will be manufactured and provided under the responsibility of
the sponsor.
Up-titration Guidelines
Instructions for up-titration of erdafitinib, in the absence of erdafitinib related toxicity, based on
the serum phosphate level at Cycle 1 Day 14 are provided below and in Figure 5. For children aged
≥6 to <12 years and adolescents aged ≥12 to <15 years, an additional blood sample will be drawn
at Cycle 2 Day 7 for determination of the serum phosphate level and the need for dose
modification.
Subjects with a serum phosphate level higher than 9.00 mg/dL (>2.91 mmol/L) will withhold
erdafitinib treatment, with at least weekly assessment of serum phosphate until it returns to less
than 7.00 mg/dL (<2.25 mmol/L) while initiating treatment with a phosphate binder such as
sevelamer (see Table 8 for detailed guidelines regarding further treatment).
Figure 5: 
Instructions for up-titration of erdafitinib based on serum phosphate levels
Note: in presence of erdafitinib-related toxicities, the investigator may choose to maintain the same dose of erdafitinib without
up-titration.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
56
Status: Approved, Date: 22 February 2023
Adult subjects and adolescent subjects aged ≥15 to <18 years
 
Adult subjects and adolescent subjects aged ≥15 to <18 years with a serum phosphate level
between 7.00 to 8.99 mg/dL (2.25 mmol/L to 2.90 mmol/L) on Cycle 1 Day 14 will increase
the erdafitinib dose from 8 mg once daily to 9 mg once daily, while concurrently initiating
treatment with a phosphate binder such as sevelamer (see Table 8 for details).
 
Adult subjects and adolescent subjects aged ≥15 to <18 years with a serum phosphate level
less than 7.00 mg/dL (<2.25 mmol/L) will increase the erdafitinib dose to 9 mg once daily.
No concomitant treatment is required for these subjects.
Adolescent subjects aged ≥12 to <15 years
 
Adolescent subjects aged ≥12 to <15 years with a serum phosphate level between 7.00 to
8.99 mg/dL (2.25 mmol/L to 2.90 mmol/L) will increase the erdafitinib dose from 5 mg once
daily to 6 mg once daily on Cycle 1 Day 14 or Cycle 2 Day 7, and further from 6 mg once
daily to 8 mg once daily on Cycle 2 Day 7 (for those already up-titrated to 6 mg on Cycle 1
Day 14), while concurrently initiating treatment with a phosphate binder such as sevelamer
(see Table 8 for details). This 2-step up-titration is step-wise, ie, no subjects will be allowed
to directly up-titrate from 5 mg to 8 mg.
 
Adolescent subjects aged ≥12 to <15 years with a serum phosphate level less than 7.00 mg/dL
(<2.25 mmol/L) will increase the erdafitinib dose from 5 mg once daily to 6 mg once daily on
Cycle 1 Day 14 or Cycle 2 Day 7, and further from 6 mg once daily to 8 mg once daily on
Cycle 2 Day 7 (for those already up-titrated to 6 mg on Cycle 1 Day 14). This 2-step
up-titration is step-wise, ie, no subjects will be allowed to directly up-titrate from 5 mg to
8 mg. No concomitant treatment is required.
Children aged ≥6 to <12 years
 
Children aged ≥6 to <12 years with a serum phosphate level between 7.00 to 8.99 mg/dL
(2.25 mmol/L to 2.90 mmol/L) will increase the erdafitinib dose from 3 mg once daily to 4 mg
once daily on Cycle 1 Day 14 or Cycle 2 Day 7, and further from 4 mg once daily to 5 mg
once daily on Cycle 2 Day 7 (for those already up-titrated to 4 mg on Cycle 1 Day 14), while
concurrently initiating treatment with a phosphate binder such as sevelamer (see Table 8 for
details). This 2-step up-titration is step-wise, ie, no subjects will be allowed to directly up-
titrate from 3 mg to 5 mg.
 
Children aged ≥6 to <12 years with a serum phosphate level less than 7.00 mg/dL
(<2.25 mmol/L) will increase the erdafitinib dose from 3 mg once daily to 4 mg once daily on
Cycle 1 Day 14 or Cycle 2 Day 7, and further from 4 mg once daily to 5 mg once daily on
Cycle 2 Day 7 (for those already up-titrated to 4 mg on Cycle 1 Day 14). This 2-step up-
titration is step-wise, ie, no subjects will be allowed to directly up-titrate from 3 mg to 5 mg.
No concomitant treatment is required.
If a dose is missed, then it can be taken up to 6 hours after the scheduled time; the subject may
return to the normal schedule the following day. If it has been more than 6 hours since the missed
dose, then that dose should be skipped, and the subject should continue treatment at the scheduled
time the next day. If vomiting occurred with drug administration, no replacement dose will be
taken and any such event that occurs up to 4 hours following dose administration must be recorded
on the electronic case report form (eCRF).

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
57
Status: Approved, Date: 22 February 2023
The study drug will be dispensed at the first visit of each cycle. All study drug doses dispensed
must be captured in the source documents, and the eCRF. Unused study drug in the issued bottles
and empty bottles must be returned to the site at each study visit. Study drug must be returned to
the site when a subject discontinues study treatment. Returned tablets may not be re-issued in this
study or outside the study (follow study drug accountability guidelines in the Site Investigational
Product Manual).
The exposure of erdafitinib is predicted to increase by 50% in subjects with the CYP2C9 *3/*3
genotype, estimated to be 0.4% to 3% of the population among various ethnic groups. Therefore,
monitor for increased adverse reactions in subjects who are known or suspected to have
CYP2C9*3/*3 genotype. Dose titration is guided by serum phosphate levels in all subjects
irrespective of genotype; therefore, the implications of higher exposures of erdafitinib including
safety may be addressed.
6.2. 
Preparation/Handling/Storage/ Accountability
Preparation/Handling/Storage
Refer to the pharmacy manual/study site Investigational Product Manual and the Investigational
Product Preparation Instructions for additional guidance on study drug preparation, handling, and
storage.
Accountability
The investigator is responsible for ensuring that all study drug received at the site is inventoried
and accounted for throughout the study. The dispensing of study drug to the subject, and the return
of study drug from the subject (if applicable), must be documented on the intervention
accountability form. Subjects, or their legally acceptable representatives where applicable, must
be instructed to return all original containers, whether empty or containing study drug. All study
drug will be stored and disposed of according to the sponsor's instructions. Study-site personnel
must not combine contents of the study drug containers.
Study drug must be handled in strict accordance with the protocol and container label, and must
be stored at the study site in a limited-access area or in a locked cabinet under appropriate
environmental conditions. Unused study drug, and study drug returned by the subject, must be
available for verification by the sponsor's study site monitor during on-site monitoring visits. The
return to the sponsor of unused study drug, or used returned study drug for destruction, will be
documented on the intervention return form. When the study site is an authorized destruction unit
and study drug supplies are destroyed on-site, this must also be documented on the intervention
return form.
Potentially hazardous materials such as used ampules, needles, syringes, vials, or infusion bags
containing hazardous liquids, should be disposed of immediately in a safe manner and therefore
will not be retained for intervention accountability purposes.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
58
Status: Approved, Date: 22 February 2023
Study drug should be dispensed under the supervision of the investigator or a qualified member of
the study-site personnel, or by a hospital/clinic pharmacist. Study drug will be supplied only to
subjects participating in the study. Returned study drug must not be dispensed again, even to the
same subject. Whenever a subject brings his or her study drug to the study site for pill count, this
is not seen as a return of supplies. Study drug may not be relabeled or reassigned for use by other
subjects. The investigator agrees neither to dispense the study drug from, nor store it at, any site
other than the study sites agreed upon with the sponsor.
6.3. 
Measures to Minimize Bias: Randomization and Blinding
Randomization will not be used in this study. Subjects will be enrolled into the study by the
Interactive Web Response System (IWRS).
6.4. 
Study Drug Compliance
The investigator or designated study personnel will maintain a log of the amount of study drug
dispensed and returned. Subjects or their parent/guardianwill also record the date and time of each
daily erdafitinib dose on a diary card. Drug supplies will be inventoried and accounted for
throughout the study.
Subjects will receive instructions on compliance with study treatment at the Cycle 1 Day 1 visit,
including dosing and use of the diary card. On PK sampling days, record the time of erdafitinib
intake as accurately as possible. On days when the subject visits the study center for dose
administration or PK sampling, the investigator or designee will supervise administration of the
study drug and the exact time of administration will be recorded in the CRF. During the study, the
investigator or designated study research staff will be responsible for providing additional
instruction to reeducate any subject who is not compliant with the study drug schedule.
6.5. 
Concomitant Therapies
Concomitant therapies must be recorded at the time of full-study screening, during the study, and
up to 30 days after the last dose of study drug. All therapies (prescription or over-the-counter
medications) continued at the start of the study or started during the study and different from the
study drug, including prior anticancer therapy, must be recorded in the CRF.
Caution should be exerted for subjects taking anti-coagulant therapies (see Section 6.5.3). Frequent
monitoring for international normalized ratio (INR) is allowed at the treating physician’s
discretion. The sponsor must be notified in advance, or as soon as possible thereafter, of any
instances where prohibited medications are administered.
6.5.1. 
Permitted Medications
Permitted medications are to be recorded at the time of screening (within 30 days prior to the first
dose of study drug), throughout the study, and up to 30 days after the last dose of study drug in the
appropriate section of the eCRF.
 
Symptomatic treatment: Supportive care, such as antibiotics, analgesics, transfusions, diet,
etc., and concomitant medications for the symptomatic treatment of related toxicities (Grade 1

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
59
Status: Approved, Date: 22 February 2023
to 4) may be administered according to the standard of care at the site, and the treating
physician’s discretion, as clinically indicated.
 
Prophylactic medication: Appropriate prophylactic antiemetic regimens may be provided if
required, in accordance with institutional practice and current European Society of Medical
Oncology guidelines.
 
Chronic supportive therapies: Ongoing bisphosphonates and denosumab or other supportive
therapies are permitted. Subjects with breast cancer or prostate cancer who progressed while
receiving hormonal therapy may continue the same hormonal therapy adjunctively, providing
the same therapy was ongoing for at least 6 months prior to the first dose of study drug.
 
Palliative radiotherapy: Localized radiotherapy for symptomatic control is permitted but
should not include definitive radiation to target lesions.
 
Surgical Procedures: Surgery or biopsy of target lesions is not permitted.
 
COVID-19 vaccination: Note: administration of non-live vaccines approved or authorized for
emergency use (eg, COVID-19) by local health authorities are allowed before or during this
study.
6.5.2. 
Prohibited Medications
The following concomitant medications are prohibited during the study. The sponsor must be
notified in advance, or as soon as possible thereafter, of any instances in which prohibited therapies
were administered.
 
Concurrent investigational agents during the Treatment Phase
 
Concurrent antineoplastic agents or hormonal anticancer therapy (except as noted in
Section 6.5.1) during the Treatment Phase
6.5.3. 
Precautions for Concomitant Medications
The following precautions are advised:
 
Based on in vitro data, erdafitinib is metabolized by cytochrome CYP2C9 and CYP3A4. A
clinical drug-drug interaction study showed that on average, erdafitinib exposure (Cmax  and
AUC) was increased 5% and 34%, respectively, when co-administered with itraconazole (a
strong inhibitor of CYP3A4) and 21% and 48%, respectively, when co-administered with
fluconazole (a moderate inhibitor of CYP2C9). For this reason, strong CYP3A4 and moderate
CYP2C9 inhibitors should be used with caution (see Section 10.10). Consider alternative
therapies with no or minimal CYP2C9 or CYP3A4 inhibition potential during treatment with
erdafitinib. If co-administration of a moderate inhibitor of CYP2C9 or strong inhibitor of
CYP3A4 is unavoidable, monitor the subject closely for adverse reactions and consider dose
modifications accordingly. If the strong inhibitor is discontinued, the erdafitinib dose may be
increased in the absence of drug-related toxicity.
Based on in vitro data, erdafitinib is metabolized by cytochrome CYP2C9 and CYP3A4. The
impact of moderate CYP2C9 inducers and strong CYP3A4 inducers (such as rifampin) on
erdafitinib was not clinically studied. The concomitant use of these agents with erdafitinib
should be avoided (see Section 10.10).

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
60
Status: Approved, Date: 22 February 2023
Co-administration of erdafitinib with moderate CYP3A inducers may decrease erdafitinib
exposure. Caution should be exercised for concomitant administration of erdafitinib and these
agents (see Section 10.10). A comprehensive list of CYP3A4/2C9 inducers is provided in
Section 10.10 and in http://medicine.iupui.edu/CLINPHARM/ddis/main-table; however, both
these references may not be exhaustive and up-to-date at any given time. Please consult the
product information of ongoing and new concomitant medications for the most accurate
information on potential strong inducers of CYP3A4 and CYP2C9.
 
Until further data become available, concomitant use of erdafitinib with CYP3A4 substrates
with narrow therapeutic indices should be avoided.
 
Erdafitinib was shown to inhibit, in in vitro experiments, human P-glycoprotein (P-gp) at
concentrations achieved at therapeutic doses in humans. If the compound is administered with
drugs that are substrates of P-gp, there is the potential for observing increased concentrations
of the substrate drug. Caution should be exercised for co-administered drugs that are P-gp
substrates; separate erdafitinib administration by at least 6 hours before or after administration
of P-gp substrates with narrow therapeutic index.
 
Erdafitinib was shown to be an OCT2 inhibitor in vitro. PBPK simulations with metformin,
an OCT2 substrate, predicted a lack of clinically relevant interaction with erdafitinib.
However, until further data are available, consider reducing the dose of OCT2 substrates or
consider alternative agents based on tolerability.
 
For subjects taking erdafitinib: medications known to increase serum levels of phosphate, such
as potassium phosphate supplements (oral or IV), vitamin D supplements, antacids, and
phosphate-containing enemas and laxatives (oral/rectal) thought to increase serum phosphate
levels: use with caution in case of strong medical need and when the benefit outweigh the risk;
check phosphate levels regularly during treatment.
6.6. 
Dose Modifications
Treatment with erdafitinib should be discontinued or modified based on erdafitinib-related toxicity
as described in Table 3. For eye, skin/nail, dry mouth/mucositis, and phosphate toxicity, specific
recommendations in the management guidelines are provided in Section 6.6.1.
Table 3: 
Erdafitinib Dose Modification Rules Based on Erdafitinib-related Toxicity Severity
Erdafitinib-
related
Toxicity Grade
Action 
Dose modification after resolution of AE  
1 
None 
Continue same dose.
2 
None, 
or 
consider 
interruption if the toxicity 
is considered clinically 
significant
If interrupted, restart at same dose if toxicity is completely
resolved to baseline or consider restarting at 1 dose lowera if
not completely resolved to baseline (but resolved to Grade 1).
3 
Interrupt drug 
Restart at 1 dose lowera if recovered to baseline (to ≤Grade 1
or back to baseline for non-hematologic toxicity) within 28
days; restart at 2 doses lowera if not completely resolved to
baseline (but resolved to Grade 1) within 28 days.
Discontinue drug if unresolved for >28 days.
4 
Interrupt drug 
Discontinue.
a Please refer to Table 4.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
64
Status: Approved, Date: 22 February 2023
Table 8: 
Guidelines for Management of Serum Phosphate Elevation
Serum Phosphate
Level 
Study Drug Management 
Symptom Management
<5.50 mg/dL 
(<1.75 mmol/L)
(Grade 0)
Continue erdafitinib treatment. 
None.
5.50-6.99 mg/dL 
(1.75-2.24 
mmol/L)
(Grade 1)
Continue erdafitinib treatment. 
Restriction of phosphate intake to 600 –
800 mg/day.
7.00-8.99 mg/dL 
(2.25-2.90 
mmol/L) 
(Grade 2) 
Continue erdafitinib treatment. 
A dose reduction will be implemented for
persistent a hyperphosphatemia (defined as 
serum phosphate ≥7.00 mg/dL for a period of 
2 months) or if clinically necessary (eg, in the 
presence of additional adverse events linked
to hyperphosphatemia or electrolyte 
disturbances) 
Restriction of phosphate intake to 600 –
800 mg/day.
Adults: Start sevelamer 800 to 1,600 mg
TID with food until phosphate level is
<7.00 mg/dL.
Children and adolescents: Start sevelamer
400 mg TID for BSA 0.75 m2, 800 mg
TID for BSA ≥0.75 to <1.2 m2, and
1,600 mg for BSA ≥1.2 m2 with food.
Titrate up/down by 200 mg for BSA
0.75 m2, 400 mg TID for BSA ≥0.75 to
<1.2 m2, and 800 mg for BSA ≥1.2 m2
until phosphate level is <7.00 mg/dL. b
9.00-10.00 mg/dL 
(2.91- 
3.20 mmol/L) 
(Grade 3) 
Withhold c erdafitinib treatment until serum 
phosphate level returns to 7.00 mg/dL (weekly 
testing recommended).
Re-start treatment at the same dose level. 
A dose reduction will be implemented for
persistent a hyperphosphatemia (defined as 
serum phosphate ≥9.00 mg/dL for a period of 
1 month) or if clinically necessary (eg, in the 
presence of additional adverse events linked 
to hyperphosphatemia or electrolyte 
disturbances) 
Restriction of phosphate intake to 600 –
800 mg/day.
Adults: Sevelamer up to 1,600 mg TID
with food until serum phosphate level
returns to <7.00 mg/dL.
Children and adolescents: Start sevelamer
400 mg TID for BSA 0.75 m2, 800 mg
TID for BSA ≥0.75 to <1.2 m2, and
1,600 mg for BSA ≥1.2 m2 with food.
Titrate up/down by 200 mg for BSA
0.75 m2, 400 mg TID for BSA ≥0.75 to
<1.2 m2, and 800 mg for BSA ≥1.2 m2
until phosphate level is <7.00 mg/dL. b
>10.00 mg/dL 
(>3.20 mmol/L) 
(Grade 4) 
Withhold c erdafitinib treatment until serum 
phosphate level returns to 7.00 mg/dL (weekly 
testing recommended).
Re-start treatment at the first reduced dose
level.
If persistent a hyperphosphatemia
(≥10.00 mg/dL) for >2 weeks, erdafitinib
should be discontinued permanently.
Medical management as clinically
appropriate.
Significant 
alteration in 
baseline renal 
Erdafitinib should be discontinued 
permanently. (In situations where the subject 
is having clinical benefit and the investigator
and the sponsor’s medical monitor agree that
Medical management as clinically
appropriate.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
65
Status: Approved, Date: 22 February 2023
Table 8: 
Guidelines for Management of Serum Phosphate Elevation
Serum Phosphate
Level 
Study Drug Management 
Symptom Management
function or Grade 3 
hypocalcemia 
continuation of treatment is in the best interest
of the subject, the drug may be re-started at
2 dose levels lower if appropriate. Follow
other recommendations described above,
Section 6.6.)
Note: These are general guidelines that are based on emerging data and consensus experience of participating investigators or
the experts in the field. The treating physicians must use clinical judgment and local standard of care to decide the best way to
manage phosphate elevation. If sevelamer hydrochloride (Renagel®) is not available, use of other phosphate binders (non-
calcium containing) based on the local standard is recommended, including sevelamer carbonate (Renvela) or lanthanum
carbonate (Fosrenol®). These guidelines will be updated based on emerging data. Additional information on phosphorous in
foods by class of food can also be found at www.permanente.net/homepage/kaiser/pdf/42025.pdf. Additional information for
phosphate management and diet can be found at the National Kidney Foundation website
(http://www.kidney.org/atoz/content/phosphorus.cfm).
a. Persistent hyperphosphatemia is considered to be more than 1 sequential phosphate value above the cut-off.
b. Pediatric dosing for sevelamer based on Fathallah-Shaykh 2018.
c. Study drug interruptions for hyperphosphatemia suggested to be 7 days in duration.
6.6.1.2. 
Guidelines for the Management of Dry Mouth and Mucositis
Guidelines for the clinical management of dry mouth (xerostomia) and mucositis are provided in
Table 9 and Table 10, respectively.
General prophylaxis for dry mouth and oral mucositis:
- Good oral hygiene
- Use a soft toothbrush
- Avoidance of spicy, acidic, hard, and hot food and beverages
- Use of mild-flavored toothpastes
- Use of salt and baking soda mouthwashes 3 or 4 times per day
- Water soluble lubrication agents like artificial saliva (for xerostomia or dry mouth)

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
66
Status: Approved, Date: 22 February 2023
Table 9: 
Guidelines for Management of Dry Mouth (Xerostomia)
Grade and Definition 
Study Drug (Erdafitinib) Management 
Symptom Management
Grade 1: symptomatic (eg, dry or 
thick saliva) without significant 
dietary alteration; unstimulated
saliva flow >0.2 mL/min
Continue erdafitinib at current dose. 
Sorbitol lozenges as
needed
Grade 2: moderate symptoms; oral 
intake alterations (eg, copious 
water, other lubricants, diet limited 
to purees or soft, moist foods); 
unstimulated saliva 0.1 to 
0.2 mL/min
Continue erdafitinib at current dose. 
Sorbitol lozenges as
needed and Cevimeline
30 mg TID or
Pilocarpine 5 mg TID,
orally
Grade 3: inability to adequately 
aliment orally; tube feeding or TPN 
indicated; unstimulated saliva less 
than 0.1 mL/min  
Hold erdafitinib (for up to 28 days), with 
weekly reassessments of clinical condition. 
When resolved to ≤Grade 1 or baseline, 
restart at 1 dose level below in consultation 
with the medical monitor. 
Sorbitol lozenges as
needed and Cevimeline
30 mg TID or
Pilocarpine 5 mg TID,
orally
Grade 4: life-threatening 
consequences, urgent intervention 
indicated
Discontinue erdafitinib. 
Evaluation and therapy
as clinically indicated
Table 10:  Guidelines for the Management ofOral Mucositis
Grade 
Study Drug (Erdafitinib) Management 
SymptomManagement
Grade 1 
Continue erdafitinib at current 
dose. 
 
Continue general prophylaxis
recommendations
 
Dexamethasone solution (0.5 mg/5mL
solution) swish and spit QID or similar
solution that is available in your
country/territory and lidocaine 2-5%
jelly or solution.
 
Consider clotrimazole/nystatin if
subjects are at risk of developing oral
candidiasis.
Grade 2 
 
Consider holding erdafitinib if the 
subject has other study-drug related 
concomitant Grade 2 AEs. 
 
Hold erdafitinib if the subject was 
already on symptom management 
(dexamethasone solution swish and 
spit and lidocaine 2%-5% jelly or 
solution) for more than a week. 
 
If the erdafitinib is withheld, 
reassess in 1-2 weeks.
 
If this is the first occurrence of
toxicity and resolves to ≤Grade 1 or
baseline within 2 weeks, restart at
same dose.
 
If recurrent event or takes >2 weeks
to resolve to ≤Grade 1 or baseline,
then restart at 1 dose level below.
 
Dexamethasone solution (0.5 mg/5mL
solution) swish and spit QID or similar
solution that is available in your
country/territory and lidocaine 2-5%
jelly or solution.
 
Consider concomitant etiologies such as
oral candidiasis, oral herpes and
recommend appropriate anti-fungal or
anti-viral agents.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
67
Status: Approved, Date: 22 February 2023
Table 10:  Guidelines for the Management of Oral Mucositis
Grade 
Study Drug (Erdafitinib) Management 
SymptomManagement
Grade 3 
 
Hold erdafitinib, with reassessments 
ofclinical condition in 1-2 weeks. 
 
When resolves to ≤Grade 1 or 
baseline, restart at 1 dose level 
below in consultation with the 
medical monitor.  
 
Dexamethasone solution (0.5 mg/5mL
solution) swish and spit QID or similar
solution that is available in your
country/territory and lidocaine 2%-5%
jelly or solution.
 
Consider pain management strategies.
 
Consider IV hydration.
Grade 4 
Discontinue erdafitinib. 
Evaluation and therapyas clinically
indicated.
AE=adverse event; QID=four times a day.
6.6.1.3. 
Guidelines for the Management of Dry Skin and Skin Toxicity
Guidelines for the management of dry skin are provided in Table 11.
General prophylaxis for dry skin and skin toxicity:
- Avoid unnecessary exposure to sunlight and excessive use of soap.
- Avoid bathing in excess; use tepid rather than hot water.
- Use moisturizers regularly; apply thick, alcohol-free and oil-in-water based emollient
cream on exposed and dry areas of the body.
- Avoid perfumed products, bubble bath, perfumed soaps, and take breaks from shaving.
- Use broad spectrum sunscreen with a skin protection factor (SPF) ≥15.
- Wear cotton clothes next to skin rather than wool, synthetic fibers, or rough clothing.
- Use occlusive alcohol-free emollient creams (jar or tub) for treatment of mild/moderate
xerosis.
- For scaly areas, use exfoliants (ammonium lactate 12% or lactic acid cream 12%).

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
68
Status: Approved, Date: 22 February 2023
Table 11: 
Guidelines for Management of Dry Skin
Grade and Definition 
Study Drug (Erdafitinib) Management Symptom Management
Grade 1: Dry skin covering 
less than 10% body surface 
area (BSA) and no associated 
erythema or pruritus 
Continue erdafitinib at current dose. 
Use fragrance free moisturizing
cream or ointment BID over entire
body.
Use ammonium lactate 12% cream
or salicylic acid 6% cream BID
over dry/scaly/hyperkeratotic areas
such as palms and soles.
Grade 2: Dry skin covering 
10% to 30% BSA and 
associated with erythema or 
pruritis with limited 
instrumental activities of daily 
living (IADL) 
Continue erdafitinib at current dose. 
Use fragrance free moisturizing
cream or ointment BID over entire
body.
Use ammonium lactate 12% cream
or salicylic acid 6% cream BID
over dry/scaly/hyperkeratotic areas
such as palms and soles.
Use zinc oxide 13%-40% at night
for areas with fissures.
Grade 3: Dry skin covering 
>30% BSA and associated 
with pruritis; limiting self-care 
activities of daily living 
(ADL) 
Hold erdafitinib (for up to 28 days), with 
weekly reassessments of clinical 
condition. 
When resolves to ≤Grade 1 or baseline,
restart at 1 dose level below in
consultation with the medical monitor.
Use topical steroid ointment or
cream* BID and zinc oxide 13%-
40% at night for areas with fissures.
Grade 4: Dry skin with life- 
threatening consequences, 
urgent intervention indicated
Discontinue erdafitinib. 
Evaluation and therapy as clinically
indicated
* Topical Steroid Ointments: Clobetasol 0.05%, Betamethasone 0.05%, Fluocinonide 0.05%
6.6.1.4. 
Guidelines for the Management of Nail Toxicity (Onycholysis,
Onychodystrophy, and Paronychia)
Adverse events related to nails will be graded as outlined in Table 12. Guidelines for the
management of nail discoloration/loss/ridging (onycholysis/onychodystrophy) nail toxicity are
provided in Table 13. Guidelines for the management of paronychia are provided in Table 14.
Table 12: 
Grading of Nail Adverse Events
Adverse Event 
Grade 1 
Grade 2 
Grade 3 
Grade 4
Nail Changes 
(onychodystrophy) 
Nail discoloration, 
asymptomatic 
separation of the 
nail bed from the 
nail plate or nail 
loss 
Nail/finger tips 
pain, symptomatic 
separation of the 
nail bed from the 
nail plate or nail 
loss; limiting 
instrumental ADL 
Severe nail finger 
tips pain, 
symptomatic 
separation of the 
nail bed from the
nail plate or nail
loss; significantly
limiting
instrumental ADL
Life-threatening
consequences,
urgent intervention
indicated
ADL= activities of daily living

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
69
Status: Approved, Date: 22 February 2023
General prophylaxis for nail toxicity:
- Good hygienic practices, keep fingers and toes clean
- Keep nails trimmed but avoid aggressive manicuring
- Use gloves for housecleaning and gardening to minimize damage and prevent infection
- Nail polish and imitation fingernails should not be worn until the nails have grown out
and returned to normal
- Wearing comfortable shoes (wide sized shoes with room for the toes)
Table 13: 
Guidelines for Management of Nail Toxicity (Onycholysis/ Onychodystrophy)
Grade 
Study Drug (Erdafitinib) Management SymptomManagement
Grade 1 
Continue erdafitinib at current dose. 
 
Continue general prophylaxis recommendations
 
Over the counter nail strengthener OR polyurea-urea
urethane nail lacquer (Nuvail™) OR diethylene glycol
monoethylether nail lacquer (Genadur) daily.
 
Use non- alcohol-containing moisturizing creams.
Grade 2 
Consider holding erdafitinib with
reassessment in 1-2 weeks.
If first occurrence and it resolves to
≤Grade 1 or baseline within 2
weeks, restart at same dose.
If recurrent event or takes >2 weeks to
resolve to ≤Grade 1 or baseline, then
restart at 1 dose level below in
consultation with the medical monitor.
 
Manage as per Grade 1
 
For signs ofinfection (periungual edema/erythema/
tenderness or discharge), obtain bacterial cultures,
and then start the following:
o 
treatment with oral antibiotic for 2 weeks
(cefadroxil 500 mg BID, ciprofloxacin 500
mg BID, orsulfamethoxazole/ trimethoprim
BID)
AND
o 
topical antifungal lacquer daily for 6+
weeks (ciclopirox olamine 8% OR
efinaconazole 10% OR amorolfine 5%
weekly OR bifonazole/urea ointment daily)
 Silver nitrate application weekly AND topical
antibiotics AND vinegar soaksa
Grade 3 
Hold erdafitinib, with reassessment in 
1-2 weeks. 
When resolves to ≤Grade 1 or baseline, 
restart at 1 dose level belowin  
consultation with the medical monitor. 
Silver nitrate application weekly AND topical
antibiotics AND vinegar soaks.a
For signs ofinfection (periungual edema/erythema/
tenderness or discharge), obtain bacterial cultures, and
then start the following: treatment with oral antibiotic for
2 weeks (cefadroxil 500 mg BID, ciprofloxacin 500 mg
BID, or sulfamethoxazole/trimethoprim BID).
For cases ofsevere/refractoryinfection consider
intravenousantibiotics.
Considerdermatological orsurgical evaluation.
Grade 4 
Discontinue erdafitinib. 
Evaluation and therapyas clinically indicated.
a
Vinegar soaks consist ofsoaking fingers or toes in a solution ofwhite vinegar in water 1:1 for 15 minutes every
day. Examples oftopical antibiotic ointments: Mupirocin 2%, gentamycin, bacitracin zinc/polymixins B
BID=bis in die (two times each day).

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
70
Status: Approved, Date: 22 February 2023
Table 14: 
Guidelines for Management of Paronychia
Grade 
Study Drug (Erdafitinib) 
Management
Symptom Management
Grade 1 
Continue erdafitinib at 
current dose.
Topical antibiotics AND vinegar soaksa
Grade 2 
Continue erdafitinib at 
current dose. 
Consider erdafitinib holding 
if no improvement in 1 to 2 
weeks. 
When resolves to ≤Grade 1 
or baseline, restart at same 
or 1 dose level below in 
consultation with the 
medical monitor 
Topical antibiotics AND vinegar soaksa AND topical
antifungal lacquer daily for 6+ weeks (ciclopirox olamine
8% OR efinaconazole 10% OR amorolfine 5% weekly OR
bifonazole/urea ointment daily)
For signs of infection (periungual
edema/erythema/tenderness or discharge), obtain bacterial
cultures, and then start the following: treatment with oral
antibiotic for 2 weeks (cefadroxil 500 mg BID,
ciprofloxacin 500 mg BID, or sulfamethoxazole/
trimethoprim [Bactrim™ DS BID).
Grade 3 
Hold erdafitinib (for up to 
28 days), with weekly 
reassessments of clinical 
condition. 
When resolves to ≤Grade 1
or base line, restart at one 
dose level below in 
consultation with the
medical monitor.
Vinegar soaksa AND consider nail avulsion
For signs of infection (periungual
edema/erythema/tenderness or discharge), obtain bacterial
cultures, and then start the following: treatment with oral
antibiotic for 2 weeks (cefadroxil 500 mg BID,
ciprofloxacin 500 mg BID, or sulfamethoxazole/
trimethoprim [Bactrim DS BID).
For cases of severe/refractory infection consider
intravenous antibiotics.
Consider dermatological or surgical evaluation.
a Vinegar soaks consist of soaking fingers or toes in a solution of white vinegar in water 1:1 for 15 minutes every
day. Examples of topical antibiotic ointments: Mupirocin 2%, gentamycin, bacitracin zinc/polymixin B
6.6.1.5. 
Guidelines for the Management of Eye Toxicity Associated With
Vision Changes
If subject experiences an event of confirmed new retinal abnormality (such as retinal detachment,
vitreous detachment, retinal edema, retinopathy, chorioretinopathy, detachment of retinal pigment
epithelium, and detachment of macular retinal pigment epithelium) during study treatment, it must
be reported as an adverse event or a serious adverse event if Grade 3 or higher. Any new and
clinically significant symptoms, such as but not limited to, blurred vision, partial or complete loss
of vision, double vision, floaters or color spots or halos around light, change in color or night
vision, photophobia, ocular pain or stinging sensation, or foreign body sensation should be further
evaluated and managed per the guidelines in Table 15.
Amsler Grid (illustrated in Section 10.9): For any positive Amsler grid test, the subject should be
referred for a full ophthalmologic examination within 7 days. However, if the subject has an
abnormal Amsler grid test and otherwise normal ophthalmologic exam at baseline (during
Screening), a repeat ophthalmologic examination would be recommended only if, in the opinion
of the investigator, there is a likelihood of significant change from the subject’s baseline Amsler
grid test at Screening, or the subject has developed new clinical symptoms.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
71
Status: Approved, Date: 22 February 2023
Table 15: 
Guidelines for Management of Eye Toxicity
Grade and Definition 
Study Drug (Erdafitinib) Management 
Symptom Management
Grade 1: Asymptomatic 
or mild symptoms; 
clinical or diagnostic 
observations only  
Or abnormal Amsler
grid test 
Refer for an ophthalmologic examination. If an 
ophthalmologic exam cannot be performed within 7 days, 
withhold treatment with erdafitinib until an examination 
can be performed.
If there is no evidence of eye toxicity on ophthalmologic 
examination, continue erdafitinib at the same dose level. 
If diagnosis from ophthalmologic examination is keratitis
or retinal abnormality such as central serous retinopathy
(CSR)/ retinal pigment epithelial detachments (RPED), 
withhold erdafitinib until signs and symptoms have 
resolved. 
If toxicity is reversible (complete resolution or
stabilization and asymptomatic) in 4 weeks according to
ophthalmologic examination, resume erdafitinib at the next
lower dose level after consultation with the sponsor’s
medical monitor.
Retinal pigment epithelial detachment, if observed, should
be monitored at approximately 2-3-week intervals until
resolution.
Monitor for recurrence every 1 to 2 weeks for a month and
as clinically appropriate thereafter. If there is no
recurrence, then re-escalation can be considered in
consultation with the medical monitor.
Refer the subject for an
ophthalmologic
examination.
For retinal pathology
perform OCT as appropriate
and consider referral to a
retinal specialist for further
evaluation.
Follow specific treatment
per the ophthalmologist’s
recommendation.
Grade 2: Moderate; 
minimal, local, or
noninvasive
intervention indicated;
limiting age-appropriate
instrumental ADL
Visual acuity 20/40 or
better or ≤ 3 lines of
decreased vision from
baseline
Immediately withhold erdafitinib. 
If there is no evidence of drug-related corneal or retinal
pathology on ophthalmologic examination, withhold
erdafitinib until signs and symptoms have resolved.
Resume erdafitinib therapy at the next lower dose level.
If diagnosis from ophthalmologic examination is keratitis
or retinal abnormality such as CSR/RPED, withhold
erdafitinib until signs and symptoms have resolved,
stabilized, or subject is lost to follow-up or withdraws
consent (which ever happens first).
If toxicity is reversible (complete resolution or
stabilization and asymptomatic) within 4 weeks according
to ophthalmologic examination, resume erdafitinib at the
next lower dose level after consultation with the sponsor’s
medical monitor.
Retinal pigment epithelial detachment, if observed, should
be monitored at approximately 2-3-week intervals until
resolution.
Monitor for recurrence every 1 to 2 weeks for a month and
as clinically appropriate thereafter. If there is no
recurrence, then re-escalation can be considered in
consultation with the medical monitor.
Refer subject to an
ophthalmologist for
evaluation with an
ophthalmologic
examination.
For retinal pathology,
perform OCT as appropriate
and consider referral to a
retinal specialist for further
evaluation.
Follow specific treatment
per the ophthalmologist’s
recommendation.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
72
Status: Approved, Date: 22 February 2023
Table 15: 
Guidelines for Management of Eye Toxicity
Grade and Definition 
Study Drug (Erdafitinib) Management 
Symptom Management
Grade 3: Severe or 
medically significant 
but not immediate 
sight-threatening; 
hospitalization or 
prolongation of existing 
hospitalization 
indicated; disabling; 
limiting self-care ADL
Visual acuity worse 
than 20/40 or > 3 lines 
of decreased vision
from baseline
If the toxicity is Grade 3, report as a serious adverse event 
and withhold erdafitinib. If the toxicity is Grade 3 and 
reversible (complete resolution or stabilization and 
asymptomatic) within 4 weeks and the subject is having 
clinical benefit, and the investigator and the sponsor’s 
medical monitor agree that continuation of treatment is in
the best interest of the subject, then erdafitinib may be
resumed at 2 dose levels lower if appropriate.
Retinal pigment epithelial detachment, if observed, should 
be monitored at approximately 2-3-week intervals until 
resolution.
Monitor for recurrence using appropriate investigations 
every 1 to 2 weeks for a month and as clinically 
appropriate thereafter. For cases of recurrence, consider
permanent discontinuation.
Refer subject to an
ophthalmologist for
evaluation with an
ophthalmologic
examination.
For retinal pathology,
perform OCT as appropriate
and consider referral to a
retinal specialist for further
evaluation.
Follow specific treatment
per the ophthalmologist’s
recommendation.
Grade 4: Sight- 
threatening
consequences; urgent
intervention indicated;
blindness (20/200 or
worse) in the affected 
eye 
Visual acuity 20/200 or
worse in affected eye
Permanently discontinue treatment with erdafitinib. 
Report as a serious adverse event and monitor resolution of
the event until complete resolution, stabilization or the
subject is lost to follow-up or withdraws consent (which
ever happens first).
Promptly refer subject to an
ophthalmologist for
evaluation with an
ophthalmologic
examination.
Follow specific treatment
per the ophthalmologist’s
recommendation.
ADL=Activities of Daily Living, OCT= Optical Coherence Tomography
6.6.1.6. 
Guidelines for the Management of Dry Eye
 
General considerations: Avoid unnecessary exposure to sunlight and use sunglasses in bright
light.
 
Prophylactic management: Frequent use of artificial tear substitutes and ocular demulcents
is strongly recommended, ie, every 2 hours during awake time.
 
Reactive management:
 
Withhold erdafitinib for Grade 3 toxicity
 
Artificial tear substitutes if not started, every 2 hours during awake time
 
Ocular demulcents
 
Severe treatment-related dry eye should be evaluated by an ophthalmologist

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
73
Status: Approved, Date: 22 February 2023
6.7. 
Study Drug After Study Completion
Once the end of data collection timepoint (see Section 5.5) has been achieved, follow-up of
subjects will end, and data collection will conclude. Only serious adverse events will be reported
in the company safety repository (See Appendix 13). Subjects in the Treatment Phase who are
continuing to derive benefit from study treatment as determined by their investigator may continue
to receive access to study treatment either on this study, with only data collection of serious adverse
events in the company safety repository (see Section 5.5) via LTE phase (see Appendix 13) or a
post-trial access program, when permitted by local regulations. Provision may continue until the
subject can commercially access study treatment within the local healthcare system, until a
decision is made not to pursue the studied indication, until the investigator decides it is in the best
interest of the subject that study treatment be discontinued, or until 2 years after local marketing
authorization is obtained for the studied indication, whichever comes first.
7. 
DISCONTINUATION OF STUDY DRUG AND SUBJECT
DISCONTINUATION/WITHDRAWAL
A subject will be considered as having completed the study if the subject has died during the study
or has not been withdrawn from the study by the end of the study.
7.1. 
Discontinuation of Study Drug
A subject's study drug must be discontinued if:
 
The subject withdraws consent or assent to receive study drug
 
The investigator believes that for safety reasons or tolerability reasons (eg, adverse event) it
is in the best interest of the subject to discontinue study drug
 
The subject becomes pregnant; discontinuation of study treatment in this instance should be
discussed with the medical monitor
 
Progression of disease is assessed
Exception: if the investigator and medical monitor agree that continuation of treatment is in
the best interest of the subject considering the terminal nature of the underlying disease, he/she
may receive treatment until such time as the treating physician and the medical monitor agree
that further continuation of treatment is no longer beneficial to the subject.
 
The subject refuses further treatment with the study drug
 
The sponsor terminates the study
 
Investigator decision approved by the sponsor
If a subject discontinues study drug for any reason, an End-of-Treatment Visit should be conducted
30 (+7 days) after the subject’s last dose of study drug. The primary reason for treatment
discontinuation will be clearly documented in the subject’s medical record and recorded in the
CRF. Study drug assigned to the subject who discontinued study drug may not be assigned to
another subject.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
74
Status: Approved, Date: 22 February 2023
7.2. 
Subject Discontinuation/Withdrawal From the Study
A subject will be withdrawn from the study for any of the following reasons:
 
Lost to follow-up
 
Withdrawal of consent
When a subject withdraws before study completion, the reason for withdrawal is to be documented
in the CRF and in the source document.
A subject (as well as guardian for children and adolescent subjects) declining to return for
scheduled visits does not necessarily constitute withdrawal of consent. Alternate follow-up
mechanisms that the subject agreed to when signing the consent form apply as local regulations
permit.
7.2.1. 
Withdrawal From the Use of Research Samples
The subject or their legal representative may withdraw consent for use of samples for future
research. In such a case, samples will be destroyed after they are no longer needed for the clinical
study. Details of the sample retention for research are presented in the ICF.
8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
The Schedule of Activities (Section 1.3 for Adults and Section 1.4 for Children and Adolescents)
summarizes the frequency and timing of safety, efficacy, PK, biomarker, and other measurements
applicable to this study. Patient-reported outcome questionnaires should be completed before any
other assessments at each clinic visit.
The number of samples and the blood volume will vary depending on the number of cycles of the
study drug that the subject receives. The total blood volume to be collected from each subject will
be approximately 230 mL for adults and 275 mL for children and adolescents over 6 cycles
(including the screening and end of study visits, approximately 15 mL is collected at each
additional cycle). (See Section 4.2.4 for additional information regarding the blood volume).
Unscheduled blood samples may be required for safety issues of individual subjects.
Study-Specific Materials
The investigator will be provided with the following supplies:
 
Erdafitinib Investigator's Brochure
 
Pharmacy manual/study site Investigational Product Manual and the Investigational Product
Preparation Instructions
 
Laboratory manual
 
National Cancer Institute Common Terminology Criteria for Adverse Events
(NCI-CTCAE) Version 5 or higher

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
75
Status: Approved, Date: 22 February 2023
 
PRO completion guidelines
 
Imaging Guidelines
 
IWRS Manual
 
Electronic data capture (eDC) Manual
 
eSource Manual
 
Sample ICFs
8.1. 
Study Procedures
8.1.1. 
Screening Phase
The Screening Phase will consist of a Molecular Eligibility Screening Period and a Full Study
Screening Period. The consent process for the Molecular Eligibility Screening Period may occur
in 1 of 3 ways:
 
If archived tissue is available, the Molecular Eligibility Informed Consent Form (ICF) is
signed.
 
If a new tissue biopsy is required, the Full-study ICF is signed.
 
If a historical report (local testing) is available indicating the subject is molecularly eligible
for the study, upon sponsor review and approval, the Molecular Eligibility Screening Period
is complete and the subject signs the Full-study ICF, or the Full-study ICF and Molecular
Eligibility ICF are combined and signed at the same time.
The Full Study Screening Period starts within 30 days of the first dose of study drug on Cycle 1
Day 1. All subjects who are eligible for the study based on molecular screening must sign the
Full-study ICF.
8.1.1.1. 
Molecular Eligibility Screening Period
Prior to implementation of Amendment 4, central testing for FGFR alterations was performed on
subject tissue samples from the tumor histologies listed in Figure 6. Subjects with any solid tumor
histology (excluding urothelial cancer) may meet molecular eligibility  by submitting a
local/historical test result showing an FGFR mutation or fusion. (The World Health Organization
[WHO] Classification of Tumours will be used to categorize tumor histologies in this study.)
Consent for molecular eligibility screening (but not full study screening) may be performed
remotely including consent by telephone or video consultation, unless not permitted according to
local guidance.
During the Molecular Eligibility Screening Period, originally the protocol allowed for 2
approaches to determine eligibility for this study, ie, central or local molecular screening: (Starting
with Amendment 4, central molecular testing will no longer be used for all subjects.)

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
77
Status: Approved, Date: 22 February 2023
8.1.1.2. 
Full-study Screening Period
The Full Study Screening Period is 30 days before the first dose of study treatment on Cycle 1
Day 1. Subjects must meet all of the inclusion and none of the exclusion criteria in Section 5.
Retesting of abnormal laboratory values that may lead to exclusion will be allowed once. To
re-assess eligibility, retesting will take place during an unscheduled visit in the Screening Phase.
Subjects will be allowed to be re-screened only once for eligibility (both molecular and full study
eligibility) if the investigator has a valid reason (eg, true resolution of conditions previously
meeting the exclusion criteria, availability of a different tumor tissue for FGFR testing, molecular
test internal quality control failure) to re-screen and after consultation with the medical monitor.
8.1.2. 
Treatment Phase
The Treatment Phase will begin with the administration of the first dose of erdafitinib and will
continue until disease progression, intolerable toxicity, withdrawal of consent, decision by the
investigator to discontinue treatment, or the end of data collection timepoint has been achieved.
Subjects assessed with progressive disease, but for whom the treating physician strongly believes
that continuation of study treatment will provide clinical benefit, may be allowed to continue
treatment with erdafitinib after consultation with the medical monitor (please see guidelines in
Section 8.2.2). The subject will continue to follow procedures as outlined in the Schedule of
Activities and receive treatment until the treating physician and the medical monitor agree that
further continuation of treatment is no longer providing benefit to the subject.
Throughout the Treatment Phase, the investigator will assess response to therapy using RECIST
Version 1.1 or RANO. Efficacy evaluations are described in Section 8.2. For subjects who
discontinue study therapy without documented disease progression, every effort should be made
to continue monitoring their disease status by tumor imaging according to the imaging schedule,
until (1) the start of new anti-cancer treatment, (2) disease progression, (3) withdrawal of consent,
(4) death, or (5) the end of the study, whichever occurs first.
8.1.3. 
End-of-Treatment Visit
The End of Treatment Visit will be performed after the last dose of study drug is administered and
will include End-of-Treatment procedures as outlined in the Schedule of Activities. Subjects
should have the End-of-Treatment Visit completed 30 (+7) days after the last dose of study drug,
or prior to the starting any subsequent cancer treatment, except for those who have withdrawn
consent, died, or have been lost to follow up.
Once the end of data collection timepoint has been achieved, follow-up of subjects will end, and
data collection will conclude. Only serious adverse events will be reported in the company safety
repository (See Appendix 13). Subjects in the Treatment Phase who are continuing to derive
benefit from study treatment as determined by their investigator may continue to receive access to
study treatment (see Section 6.7). During this period, only serious adverse events will be reported
into the company safety repository. Additional information on reporting of adverse events is
provided in Section 10.4.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
78
Status: Approved, Date: 22 February 2023
8.1.4. 
Follow-Up Phase
All subjects who enter the Follow-up Phase will have a Follow-up Visit every 12 weeks (±7 days)
after the End-of-Treatment Visit to assess survival status and start of subsequent anti-cancer
therapy until death, withdrawal of consent, lost to follow-up, or the end of study (ie, the end of
data collection timepoint has been achieved), whichever occurs first as outlined in the Schedule of
Activities. Subjects who do not want to continue in the Follow-up Phase will be asked to complete
and sign a withdrawal ofconsent form to specify whether or not survival data may be collected.
Assessments of survival status and alternate anticancer therapies must be recorded in the eCRF. If
necessary, this visit can occur by telephone. Once the end of data collection timepoint has been
achieved, subjects will be considered to have completed the study, no further visits will occur and
data collection through the eCRF will conclude.
8.2. 
Efficacy Assessments
For adult subjects, disease assessments will be performed every 6 weeks (every 2 cycles) for the
first 12 months and then every 12 weeks (every 4 cycles) thereafter (±7-day window), as outlined
in the Schedule of Activities.
For pediatric subjects, disease assessments will be performed every 12 weeks (every 4 cycles,
±7-day window), as outlined in the Schedule of Activities. For subjects with low-grade gliomas
where a lower frequency of imaging is sufficient, a 24-week frequency (±7 days) may be adopted
after a minimum of 12 months with the sponsor’s approval. If a response (partial response or
complete response) is observed, an additional scan for confirmation is required 4  to 8 weeks
(±7-day window) after the first scan showing the response.
Assessment of responses for solid tumors will be performed according to RECIST (Version 1.1)
or RANO guidelines by investigators. For subjects who discontinue study drug before disease
progression, tumor assessments should continue as described in Section 8.1.2.
More frequent radiological assessments are allowed, if clinically indicated/desirable. Identical
methodology (computed tomography [CT] scan or magnetic resonance imaging [MRI]) should be
used for disease assessment at baseline, and throughout the course of the study, to characterize
each identified and reported lesion to document disease status. Ultrasound, fluorine
18-fluorodeoxyglucose positron emission tomography (FDG-PET), and plain x-rays are not
acceptable methods of evaluating disease response in the absence of CT or MRI scans.
If symptomatic deterioration (based on global deterioration of health status) occurs without
documentation of radiographic progression or disease progression as measured by skin lesion
assessment and photography if applicable, the clinical findings used to make this determination
must be specified in the eCRF and documented in the source documents. Every effort should be
made to document the objective progression even after discontinuation of treatment for
symptomatic deterioration. Tumor response will be reported by the investigator in the eCRF.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
79
Status: Approved, Date: 22 February 2023
8.2.1. 
Evaluations
8.2.1.1. 
RECIST and RANO Assessment of Disease
RECIST 1.1 is an accepted methodology by regulatory authorities. RECIST 1.1 will be applied by
the investigator as the primary measure for assessment of tumor response, date of disease
progression, and as a basis for all protocol guidelines related to disease status (eg, discontinuation
of study therapy). The Wen 2010 Response Assessment in Neuro-Oncology (RANO) criteria for
high-grade gliomas will be used to assess response to treatment in high-grade gliomas. The
van den Bent 2011  Response Assessment in Neuro-Oncology (RANO) criteria for low-grade
gliomas will be used to assess response to treatment in low-grade gliomas. After screening,
imaging will be repeated during the study as indicated in the Schedule of Activities.
8.2.1.2. 
Radiographic Assessment
Computed tomography (CT) scans of the chest, abdomen, pelvis, and any other location where
disease is present or suspected will be performed at Screening and during the study, except for
primary brain tumors. Magnetic resonance imaging may be used to evaluate sites of disease that
cannot be adequately imaged using CT (in cases where MRI is desirable, the MRI must be obtained
at baseline and at all subsequent response evaluations or in cases where use of CT scan is clinically
contraindicated). For all other sites of disease, MRI studies do not replace the required chest,
abdomen, and pelvic CT scans. Brain MRI will be performed at baseline for all subjects with a
history of brain metastasis or neurological symptoms. Brain MRI will be performed every
12 weeks during the study for subjects with a history of brain metastasis or any time during the
study for new or worsening neurological symptoms. Brain MRI will be performed for all subjects
with primary brain tumors at baseline and every 6 weeks for disease assessment for the first
12 months (±7-day window) and then every 12 weeks thereafter (±7-day window), as outlined in
the Schedule of Activities. Imaging should be performed as scheduled irrespective of study drug
interruptions. After discontinuation of treatment, subjects will have an End-of-Treatment Visit and
continue in the study for follow-up as outlined in Section 8.1.4.
For skin lesions that cannot be assessed radiographically, skin lesion photography may be used to
evaluate response according to RECIST 1.1 (Please refer to the Imaging Acquisition Guidelines).
8.2.2. 
Continuation of Treatment After Disease Progression
If the site study team makes an initial assessment of disease progression, and if the subject is
clinically stable, treatment with erdafitinib may be continued. In the case of imaging-based
progression (RECIST, Version 1.1 or RANO-defined disease progression) subjects may continue
to receive erdafitinib treatment if the investigator and sponsor’s clinical team agree and if the
subject is clinically stable as defined by the following criteria: absence of signs and symptoms
indicating overt disease progression, stable ECOG Performance Status grade (a comparison chart
of ECOG, Karnofsky, and Lansky performance scores is provided in Section 10.6), absence of
progressive tumor at critical anatomical sites (eg, spinal cord compression, new brain metastases)
requiring urgent alternative medical intervention. Repeat tumor imaging at least 4 weeks but no
later than 6 weeks after the first tumor imaging indicating progressive disease.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
80
Status: Approved, Date: 22 February 2023
8.3. 
Safety Assessments
The DRC will be conducting interim analyses and further safety analyses. The details regarding
the DRC are provided in the Committees Structure in Section 10.3, Regulatory, Ethical, and Study
Oversight Considerations.
Adverse events will be reported and followed by the investigator as specified in Section 8.4,
Adverse Events and Serious Adverse Events and Section 10.4, Adverse Events: Definitions and
Procedures for Recording, Evaluating, Follow-Up, and Reporting.
Any clinically significant abnormalities persisting at the end of the study/early withdrawal will be
followed by the investigator until resolution or until a clinically stable condition is reached. For
adverse events such as skin/nail and mucosal toxicity, upon subject consent, photographs may be
taken for assessment and monitoring of the toxicity.
In subjects with low-grade glioma and high-grade glioma, the frequency of seizure activity prior
to starting trial and frequency of seizure activity while enrolled on trial will be collected in eCRF.
The study will include the following evaluations of safety and tolerability according to the time
points provided in the Schedule of Activities.
8.3.1. 
History and Physical Examinations
For adult subjects, a full medical history and physical examination, including neurological
examination, height, and weight will be performed at screening. If the examination occurs more
than 7 days before the first dose of study drug, another examination should be conducted on
Cycle 1 Day 1 prior to dosing. Limited physical examinations of involved organs, neurological
examination including record of seizure activity (subjects with primary CNS tumors, CNS
metastases or other subjects at the investigator’s discretion, only), and body weight will be
performed at subsequent visits as listed in the Schedule of Activities. New abnormalities will be
recorded as AEs.
8.3.1.1. 
History and Physical Examinations for Children and Adolescent
Subjects
A full medical history and physical examination, including neurological and hip examination,
height, and weight with corresponding percentiles will be performed at screening. Height and
weight with corresponding percentiles should be documented. If the examination occurs more than
7 days before the first dose of study drug, another examination should be conducted on Cycle 1
Day 1 prior to dosing. Limited physical examinations of involved organs, neurological
examination including record of seizure activity (subjects with primary CNS tumors, CNS
metastases or other subjects at the investigator’s discretion, only), and body weight will be
performed at subsequent visits as listed in the Schedule of Activities. New abnormalities will be
recorded as AEs. For children and adolescents, Tanner Staging will be assessed as indicated on
the Children and Adolescent Schedule of Activities (see Section 1.4) until subjects turn 18 years
of age.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
81
Status: Approved, Date: 22 February 2023
Slipped Capital Femoral Epiphysis (SCFE) is a hip-joint disorder characterized by the
displacement of the capital femoral epiphysis from the femoral neck through the physis (growth
plate), a cartilaginous region at the end of the long bone. SCFE is more common in males and
occurs during adolescence, a period of increased bone growth. Given that FGFR signaling is
involved in regulation of chondrogenesis, osteogenesis, and also bone homeostasis, there is
growing evidence to suggest that exposure to FGFR tyrosine kinase inhibitors presents a potential
risk for skeletal toxicities, such as SCFE, in adolescent subjects.
Detailed history including focus on risk factors for musculoskeletal diseases, eg SCFE
(Peck 2017), should be obtained at screening; such risk factors are described below:
 Endocrine abnormalities, such as hypoparathyroidism, panhypopituitarism and
hypogonadism (Kay 2014; Blethen 1996)
 Conditions associated with growth hormone deficiency or the use of growth hormone
increases the risk of epiphysiolysis (SCFE) (de Andrade 2009)
 Radiation in proximal femoral epiphysis and chemotherapy in childhood increases the risk
of developing SCFE (Walker 1981)
 Obesity and previous history of unilateral SCFE are both risk factors for developing SCFE
(Nasreddine 2013)
 Secondary hyperparathyroidism, hypocalcemia and osteitis fibrosa in the setting of chronic
kidney disease (Schmidtt 2008)
 Accelerated growth velocity (Deng 1996)
During the Treatment Phase, subjects presenting with groin, hip, thigh, or knee pain, or changes
in ambulation should be evaluated for potential musculoskeletal disorders, especially among
subjects with accelerated growth reflected through change in percentile curves. Referral to a
pediatric orthopedic surgeon should be considered.
8.3.2. 
Vital Signs
Blood pressure (systolic and diastolic), heart rate, and temperature will be assessed. All clinically
significant abnormalities will be recorded as AEs. For children and adolescents aged ≥6 to
<18 years, height will be measured using a stadiometer and should be documented with
corresponding percentiles with weight.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
82
Status: Approved, Date: 22 February 2023
8.3.3. 
Electrocardiograms
The 12-lead electrocardiograms (ECGs) will be performed at any time during the screening period,
as well as Cycle 2 Day 1 and Cycle 4 Day 1. If possible, postdose ECGs should be recorded 2 to
4 hours after the erdafitinib dose on Cycle 2 Day 1 and on Cycle 4 Day 1. Additional ECGs may
be performed during the study as clinically indicated.
The subject should rest in a supine position for at least 5 minutes before ECG recording and should
refrain from talking or moving arms or legs. A printout of the ECG should be produced and stored
in the subject’s source documents. The 12-lead ECG recorder device used should have been
recently serviced and calibrated. The following variables should be measured: heart rate, RR, QT,
PR, QRS, QTc (Fridericia) intervals. QTcF (Fridericia) will be used for assessment of QTc
interval. For children and adolescent subjects (aged <18 years), QTc (Bazett) may be used for
assessment of QTc interval. The investigator will comment on the clinical relevance and document
this in the eCRF (along with details of clinically significant findings).
8.3.4. 
Clinical Safety Laboratory Assessments
Blood samples for serum chemistry, hematology, and pregnancy testing will be collected as noted
in Section 10.2, Clinical Laboratory Tests. The investigator must review the laboratory results,
document this review, and record any clinically relevant changes occurring during the study in the
adverse event section of the CRF.
8.3.5. 
Ophthalmologic Examination
All subjects must have an ophthalmologic examination performed at Screening by an
ophthalmologist, which should include assessment of visual acuity, fundoscopy (examination of
both central and peripheral zones should be performed), and slit lamp biomicroscopy; an Optical
Coherence Tomography (OCT) must also be performed at Screening (see the OCT Manual for
details). The Amsler grid test will also be administered by the treating physician or nurse at
Screening. A follow-up examination should be performed as clinically necessary based on the
findings of the Amsler grid tests and clinical assessment, or at regular intervals as deemed
necessary by the screening ophthalmologist.
When CSR/retinal pigment epithelial detachment (RPED) is suspected, or fundoscopic retinal
abnormalities are observed, as well as each time ocular adverse events lead to the subject being
referred to an ophthalmologist, an OCT should be performed. Fluorescein angiography could be
considered appropriate in conditions such as suspected retinal vein occlusion (RVO). In subjects
with suspected retinal pathology such as CSR or RVO, a consultation with a retina specialist
should be considered.
All images of the OCT scan and fluorescein angiography (if performed) must be stored in the
subject’s records and a redacted copy sent to the sponsor-selected central vendor for possible future
independent assessment. If only a PDF is available, please review with sponsor prior to enrollment
(refer to the central vendor manual).

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
83
Status: Approved, Date: 22 February 2023
Amsler grid (Section 10.9) testing will be administered to all subjects at Screening and during the
treatment phase according to the Schedule of Activities. Observation of wavy, broken or distorted
lines, or a blurred/missing area of vision is equivalent to a positive Amsler grid test. For any
positive Amsler grid test, subject should be referred for full ophthalmologic examination within
7 days. However, if the subject has an abnormal Amsler grid test and otherwise normal
ophthalmologic exam at baseline (during Screening), then a repeat ophthalmologic examination
would be recommended only if, in the opinion of the investigator, there is a likelihood of
significant change from the subject’s baseline Amsler grid test at Screening, or the subject has
developed new clinical symptoms.
8.3.6. 
Performance Status
Performance status will be determined at pre-specified time points listed in the applicable Schedule
of Activities (Adult or Children and Adolescent) using one of the following scales:
- ECOG performance status for adults, ie, ≥18 years of age (Section 10.5),
- Karnofsky Performance Scale for adolescents ≥16 to <18 years of age (Section 10.6), or
- Lansky Performance Scale for children and adolescents aged ≥6 to <16 years of age
(Section 10.6).
Subjects should have a repeated performance assessment at Cycle 1 Day 1 prior to dosing if the
previous one during screening occurred more than 7 days before first dosing.
8.3.7. 
Bone-related Assessments (Children and Adolescents)
For assessment of bone-related toxicities (growth plate assessment), children and adolescent
subjects (≥6 to <18 years) will undergo a plain anteroposterior (AP) radiograph of the (left or right)
tibia and AP and frog leg lateral of both hips prior to Cycle 1 Day 1.
- If subjects are found to have a closed growth plate, no further radiographs will be required.
- While on study treatment, tibia imaging will be required. If subjects are found to have an
open growth plate, repeat plain AP radiographs of the same growth plate will be performed
every 3 months for 6 months, and, thereafter, every 6 months.
- While on study treatment, hip imaging will continue to be performed every 6 months.
Additional imaging may be performed if clinically indicated (groin, hip, thigh, knee pain,
and/or difficulty ambulation). If x-ray imaging is inconclusive and symptoms persist, an
MRI should be performed for further evaluation. Referral to a pediatric orthopedic surgeon
should be considered.
Subjects with evidence of growth plate changes should have additional detailed imaging (MRI,
etc) performed to assess the degree of pathology.
For assessment of bone-related toxicities (bone age), children and adolescent subjects (≥6 to
<18 years) will undergo a plain posteroanterior (PA) radiograph of the nondominant hand and

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
84
Status: Approved, Date: 22 February 2023
wrist prior to Cycle 1 Day 1. Assessments will be conducted every 3 months for 6 months, and,
thereafter, every 6 months.
Also, for children and adolescent subjects (≥6 to <18 years), bone densitometry (DEXA scan)
should be conducted at baseline, at 6 months, at 12 months, and, thereafter, every 12 months, as
clinically indicated.
Abnormalities identified during imaging must be recorded as AEs. The investigator must consult
with the sponsor regarding any dose modification and/or discontinuation of treatment related to
these abnormalities.
8.4. 
Adverse Events and Serious Adverse Events
Timely, accurate, and complete reporting and analysis of safety information from clinical studies
are crucial for the protection of subjects, investigators, and the sponsor, and are mandated by
regulatory agencies worldwide. The sponsor has established Standard Operating Procedures in
conformity with  regulatory requirements worldwide to ensure appropriate reporting of safety
information; all clinical studies conducted by the sponsor or its affiliates will be conducted in
accordance with those procedures.
Adverse events will be reported by the subject (or, when appropriate, by a caregiver, surrogate, or
the subject's legally acceptable representative) for the duration of the study.
8.4.1. 
Time Period and Frequency for Collecting Adverse Event and Serious
Adverse Event Information
All Adverse Events
All adverse events and special reporting situations, whether serious or non-serious, will be reported
from the time a signed and dated Full-study ICF is obtained until 30 days after the subject's last
dose of study drug. Serious adverse events, including those spontaneously reported to the
investigator within 30 days after the last dose of study drug, must be reported using the Serious
Adverse Event Form. The sponsor will evaluate any safety information that is spontaneously
reported by an investigator beyond the time frame specified in the protocol.
Serious Adverse Events
All serious adverse events occurring during the study must be reported to the appropriate sponsor
contact person by study-site personnel immediately but no later than 24 hours of their knowledge
of the event.
Information regarding serious adverse events will be transmitted to the sponsor using the Serious
Adverse Event Form, which must be completed and signed by a physician from the study site, and
transmitted to the sponsor within 24 hours. The initial and follow-up reports of a serious adverse
event should be made by facsimile (fax).

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
85
Status: Approved, Date: 22 February 2023
A possible Hy’s law Case is defined by the occurrence of ALT/AST ≥3 × ULN, alkaline
phosphatase <2 × ULN together with total bilirubin ≥2 × ULN or INR >1.5 (if measured). Any
possible Hy’s Law case is considered an important medical event and should be reported as an
SAE to the sponsor in an expedited manner (Appendix 10.2), even before all other possible causes
of liver injury have been excluded.
8.4.2. 
Method of Detecting Adverse Events and Serious Adverse Events
Care will be taken not to introduce bias when detecting adverse events or serious adverse events.
Open-ended and nonleading verbal questioning of the subject is the preferred method to inquire
about adverse event occurrence.
8.4.3. 
Follow-up of Adverse Events and Serious Adverse Events
Adverse events, including pregnancy, will be followed by the investigator as specified in
Section 10.4, Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-up,
and Reporting.
8.4.4. 
Regulatory Reporting Requirements for Serious Adverse Events
The sponsor assumes responsibility for appropriate reporting of adverse events to the regulatory
authorities. The sponsor will also report to the investigator (and the head of the investigational
institute where required) all suspected unexpected serious adverse reactions (SUSARs). The
investigator (or sponsor where required) must report SUSARs to the appropriate Independent
Ethics Committee/Institutional Review Board (IEC/IRB) that approved the protocol unless
otherwise required and documented by the IEC/IRB.
8.4.5. 
Pregnancy
All initial reports of pregnancy in female subjects or partners of male subjects must be reported to
the sponsor by the study-site personnel within 24 hours of their knowledge of the event using the
appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg, spontaneous
abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are considered serious
adverse events and must be reported using the Serious Adverse Event Form. Any subject who
becomes pregnant during the study must be promptly withdrawn from the study and discontinue
further study drug. Follow-up information regarding the outcome of the pregnancy and any
postnatal sequelae in the infant will be requested. Follow-up information may continue to be
collected up to 12 months after the birth of a baby, if a congenital anomaly or significant medical
condition is diagnosed at birth.
8.4.6. 
Disease-related Events and Disease-related Outcomes Not Qualifying
as Adverse Events or Serious Adverse Events
All events that meet the definition of a SAE will be reported as SAEs, regardless of whether they
are protocol-specific assessments.
Progression of disease should not be considered an AE (or SAE). However, signs and symptoms
of disease progression or of clinical sequelae resulting from disease progression/lack of efficacy

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
86
Status: Approved, Date: 22 February 2023
that are determined by the investigator to be of clinical significance should be reported per the
usual reporting requirements (Section 10.4).
8.4.7. 
Adverse Events of Special Interest
Central serous retinopathy (CSR) is considered an adverse event of special interest. Retinal
abnormalities should be reported as adverse events or as serious adverse events if the severity is
Grade 3 or higher. Instructions for assessing vision abnormalities during the study are provided in
Section 8.3.5.
Growth disorders (including accelerated bone growth  and SCFE) and fractures in children and
adolescent subjects (≥6 to <18 years) is an adverse event of special interest for erdafitinib. Growth
disorder-related and fracture-related AEs of Grade 3 or higher severity in children and adolescents,
regardless of seriousness, will be reported to the sponsor within 24 hours (see Section 10.4.).
8.5. 
Pharmacokinetics
Venous blood samples (2 mL per visit) will be collected for the determination of plasma
concentrations of erdafitinib at the time points specified on the Schedule of Activities (Section 1.3
for Adults and Section 1.4 for Children and Adolescents). On PK sampling days Cycle 1 Day 14,
and Cycle 2 Day 14 (children and adolescents only), for morning clinic visits, morning dosing
should be withheld until after the PK sample has been obtained in the clinic. For afternoon clinic
visits, subjects should take their dose as usual and a postdose sample should be collected during
the visit. On Cycle 2 Day 1, Cycle 3 Day 1 (children and adolescents only), and Cycle 4 Day 1
(children and adolescents only), the dose should be taken in the clinic after the predose PK sample.
On Cycle 2 Day 1, a 2- to 4-hour blood sample will be collected for adults, children, and
adolescents. An approximate 1-4-mL venous blood sample will be taken together with the postdose
PK samples on Cycle 2 Day 1, 2- to 4-hour postdose (for adults), and Cycle 3 Day 1, 2-hour
postdose (for children and adolescents) for the determination of plasma protein binding data of
erdafitinib (ie, alpha-1-acid glycoproteins, total protein, and fraction unbound) (Section 1.3 for
adults and Section 1.4 for children and adolescents). On Cycle 3 Day 1, serial PK samples will be
collected at predose, and at 1h, 2h, 4h, 6h, 12h postdose in children and adolescents. The 12h
postdose sample can alternatively be collected at 24h postdose (see Section 1.4). The time of
dosing, and the time of the PK sample and protein binding sample must be recorded accurately. If
indicated by the emerging safety findings or if the scheduled PK samples are not collected due to
treatment interruption, blood samples may be collected at a later site visit (on Cycle 2 Day 14
[adults only], Cycle 3 Day 1 [adults only], or Cycle 3 Day 14). In the event of a treatment
interruption of 2 consecutive weeks or more, PK samples do not need to be collected. The
Laboratory Manual provides further information regarding handling and shipment of blood/plasma
samples.
Germline DNA will be collected for subjects on erdafitinib (see Schedule of Activities in
Section 1.3 for Adults and Section 1.4 for Children and Adolescents) from a blood sample (2 mL)
on Cycle 1 Day 14 (or later timepoint) for the purpose of CYP2C9 genotyping to allow exploration
of the effect of CYP2C9 polymorphism on the PK of erdafitinib.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
87
Status: Approved, Date: 22 February 2023
To assess the distribution of erdafitinib in the CSF in subjects with CNS tumors, one CSF sample
will be collected from a routinely scheduled CSF evaluation from subjects when feasible during
the Treatment Phase. A 2 mL sample for PK evaluation will be collected at the time of the CSF
evaluation during the treatment phase.
8.5.1. 
Analytical Procedures
Blood samples will be processed to obtain plasma for measurement of erdafitinib concentration by
a validated analytical method under the direction of the sponsor. Plasma protein binding, if needed,
will be determined by equilibrium dialysis. After dialysis, the buffer and plasma samples will be
analyzed for erdafitinib content using a qualified liquid chromatography/mass spectrometry
method by the sponsor's Bioanalytical Laboratory. The α1-AGP and other proteins will also be
measured in the plasma protein binding samples. CSF samples will be analyzed for erdafitinib
concentrations using a qualified liquid chromatography/mass spectrometry method by the
sponsor's Bioanalytical Laboratory.
8.6. 
Biomarkers
Biomarker investigations in this study include but are not limited to assessment of:
 
Circulating tumor DNA (ctDNA) from plasma to screen for changes in the levels or types of
genetic alterations observed over time, and to identify markers of intrinsic and acquired
resistance to erdafitinib
 
Assessment of alterations in non-FGFR genes in pre-treatment/archival samples and
association with response or resistance to erdafitinib
 
Serum phosphate levels as a marker of target engagement
Tumor Tissue Assessments
Tissue collected on study at screening will be used to assess biomarkers relevant to specific tumor
histologies and to determine co-occurring genomic alterations from tumor samples by DNA
sequencing analysis or alternate method.
Circulating Biomarkers
Blood samples for circulating biomarkers should be collected predose at timepoints specified in
the Schedule of Activities.
Serum phosphate levels may be monitored in subjects treated with erdafitinib as a marker of target
engagement. The Phase 1 (JNJ42756493EDI1001) and Phase 2 (JNJ42756493BLC2001) studies
of erdafitinib demonstrated that phosphate levels are a robust PD biomarker of erdafitinib target
engagement, and that achieving target increases in serum  phosphate may be associated with
clinical response to erdafitinib.
Circulating Tumor DNA
Blood for analysis of ctDNA will be collected at multiple time points on the study. Circulating
tumor DNA are fragments of DNA shed in the bloodstream during cell turnover. In cancer, a

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
88
Status: Approved, Date: 22 February 2023
fraction of the circulating DNA is from DNA shed by tumor cells. This ctDNA often harbors
somatic alterations which are reflective of the original tumor.
Circulating tumor DNA may be used to track response to treatment and the emergence of resistance
by monitoring changes in target ctDNA levels over time. Samples collected prior to and during
treatment may be screened for changes in the levels or types of genetic alterations observed over
time, and to monitor for the emergence of potential markers of resistance to erdafitinib.
Sample Collection and Analysis
Additional biomarkers (DNA, RNA, and protein) relevant to cancer may also be assessed in blood
and tissue samples collected on the study to better understand the disease and the mechanisms of
response or resistance to erdafitinib.
Adjustments in the timing of biomarker collections may be made during the study based on
emerging data.
Biomarker analyses are dependent upon the availability of appropriate biomarker assays and
emerging data. Biomarker analyses may be deferred if, during or at the end of the study, it becomes
clear that the analysis will have no scientific value, that there are not enough samples, or that there
are not enough responders to allow for adequate biomarker evaluation. In the event the study is
terminated early or shows poor clinical efficacy, completion of biomarker assessments is based on
justification and intended utility of the data.
8.7. 
Tumor Markers
If applicable for the underlying tumor type and when permitted by local regulations, serum tumor
markers (eg, carbohydrate antigen 19-9, carcinoembryonic antigen, alpha-fetoprotein) that are
assessed as part of routine care will be captured in the eCRF at baseline and until treatment
discontinuation.
8.8. 
Patient-reported Outcomes
Patients’ health-related quality of life, symptoms, functioning, and general well-being will be
captured using PRO measures (the assessments should be conducted in this order): PGIS, PGIC,
EORTC-QLQ-C30 (for subjects ≥18 years of age) or Peds FACT-Br (for subjects <18 years of
age), and EQ-5D-5L utility  and VAS. The PRO measures will be electronically collected,
according to the Schedule of Activities, to understand change over time in each cohort.
The PGIS is a single question regarding the subject report of disease severity: Considering all
aspects of your cancer symptoms right now would you say your cancer symptoms are none, mild,
moderate, severe, or very severe? The PGIS is an anchor question that will be used to establish the
magnitude of meaningful change in this study.
The PGIC is the PRO counterpart to the Clinical Global Impressions scale, (CGI), which was
published in 1976 by the National Institute of Mental Health (US) (eProvide 2019, Guy 1976). It
consists of one item taken from the CGI and adapted to the patient.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
89
Status: Approved, Date: 22 February 2023
The EORTC-QLQ-C30 (for subjects ≥18 years of age) consists of 30 core items, with the 4-point
Likert scales ranging from 1: “Not at all” to 4: “Very much” (Michelson 2000, Schwarz 2001).
There are 2 items for global health status/quality of life. Functional scales include: Physical
functioning (5 items), Role functioning (2 items), Emotional functioning (4 items), Cognitive
functioning (2 items), and Social functioning (2 items). Symptom scales/items include Fatigue
(3 items), Nausea and vomiting (2 items), Pain (2 items), Dyspnea; Insomnia; Appetite loss;
Constipation; Diarrhea; and Financial impact (1 item each). For subjects <18 years of age, the Peds
FACT-Br should be used. Peds FACT-Br consists of 4 sets of disease-specific questions pertaining
to brain neoplasms (a set of 34 to 37 questions each for child, parent of child, adolescent or parent
of adolescent; Peds FACT-Br, 2021).
The EQ-5D-5L is a generic measure of health status (Herdman 2011). For purposes of this study,
the EQ-5D-5L will be used to generate utility scores for use in cost effectiveness analyses. The
EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual
activities, pain/discomfort and anxiety/depression plus a visual analog scale rating “health today”
with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
The scores for the 5 separate questions are categorical and cannot be analyzed as cardinal numbers.
However, the scores for the 5 dimensions are used to compute a single utility score ranging from
zero (0.0) to 1 (1.0) representing the general health status of the individual. The EQ-5D-5L asks
respondents to select their response based on their current health (“today”) and takes less than
5 minutes to complete.
8.9. 
Medical Resource Utilization
Medical resource utilization data, associated with medical encounters, will be collected in the
eCRF by the investigator and study-site personnel for all subjects at the disease assessment visits.
Protocol mandated procedures, tests, and encounters are excluded. The data collected will be used
to conduct exploratory analyses that may be used to support the value story and cost-effectiveness
modeling for market access. The data collected may include:
 
Number and characteristic of diagnostic and therapeutic tests procedures (inpatient and
outpatient)
 
Number and duration of hospitalization (total length of stay [days]), including duration by
each hospital unit (intensive care unit)
 
Outpatient medical encounters (including physician, nurse practitioner or emergency room
visits, tests and procedures)
 
Please see eDC manual for more details.
9. 
STATISTICAL CONSIDERATIONS
Statistical analysis will be performed by the sponsor or under the authority of the sponsor. A
general description of the statistical methods to be used to analyze the efficacy and safety data is
outlined below. Specific details will be provided in the Statistical Analysis Plan.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
90
Status: Approved, Date: 22 February 2023
9.1. 
Statistical Hypothesis
The primary hypothesis of this study is that treatment with erdafitinib will improve ORR with a
target rate of 35% over a null rate of 15% in subjects with advanced solid tumors that harbor target
FGFR alterations in the Broad Panel Cohort, the Core Panel Cohort, or both cohorts. The
corresponding null and alternative hypotheses are as follows:
H0: ORR ≤15% vs Ha: ORR ≥35%.
9.2. 
Sample Size Determination
Approximately 280 subjects ≥12 years of age with FGFR genetic alterations will be enrolled in the
Broad Panel Cohort (approximately 240 subjects for 200 response-evaluable subjects, note that
adolescent subjects will be enrolled in the Broad Panel Cohort until the cohort is full or the sample
size cap of 30 for the tumor histology is met) and the Exploratory Cohort (approximately
40 subjects).
The primary analysis will be conducted 6 months after the first dose of the last Broad Panel Cohort
subject.
9.2.1. 
Broad Panel Cohort
The sample size of 200 response-evaluable subjects for the Broad Panel Cohort is selected based
on extensive simulations with various Bayesian hierarchical model designs to achieve
approximately 80% power to select 80% tumor histologies (eg, ≥12 of 15 tumor histologies) for
the final analysis if the true ORR is 35% for each tumor histology. For enrollment in each tumor
histology, the sample size is capped at approximately 30 subjects. For comparison, a Simon
minimax 2-stage design requires 28 subjects for Type I error rate of 0.05 and Type II error rate of
0.20. The tumor histology list for this cap, including a group of Other, is pre-defined in Table 16.
For the tumor histology that is identified as active and safe, further enrollment beyond the cap of
approximately 30 subjects may be allowed at the discretion of the DRC. These subjects will be
enrolled in separate cohorts and not included in the primary efficacy analysis of the Broad Panel
Cohort.
9.2.2. 
Cholangiocarcinoma Expansion Cohort
A DRC meeting was triggered by the cholangiocarcinoma histology approaching the predefined
cap of approximately 30 subjects. In July 2020, a DRC meeting was convened to consider
expansion of enrollment of subjects with cholangiocarcinoma. Based on review of safety and
efficacy data, the DRC recommended to continue the study and to allow expanded enrollment in
the cholangiocarcinoma histology. As a result, a Cholangiocarcinoma Cohort was added to enroll
subjects outside the Broad Panel Cohort. Approximately 30 additional subjects are intended to be
enrolled in the Cholangiocarcinoma Expansion Cohort to further characterize the clinical activity
for this histology.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
91
Status: Approved, Date: 22 February 2023
9.2.3. 
Pediatric Cohort
A separate Pediatric Cohort will enroll subjects ≥6 to <18 years of age with locally advanced or
metastatic solid tumors harboring FGFR alterations. These subjects include 1) those who have
either progressed following prior therapies and who have no acceptable standard therapies, or 2)
those who have newly diagnosed solid tumors and who have no acceptable standard therapies. A
sample size of 20 children and adolescent subjects who have either progressed following prior
therapies and who have no acceptable standard therapies (including adolescent subjects enrolled
in the Broad Panel Cohort) will be planned. 
. With an observed ORR of 35%, the
20 children and adolescent subjects will provide a 95% Clopper-Pearson CI of 15.4% to 59.2%.
In addition, approximately 6 children and adolescent subjects who have newly diagnosed solid
tumors and who have no acceptable standard therapies are anticipated to be enrolled. Note that the
enrollment in the Pediatric Cohort will be unaffected by any futility analysis for the Broad Panel
Cohort.
Note: Eligibility of adolescents ≥12 to <18 years to enroll in the Pediatric Cohort will be based on molecular
eligibility as well as whether the Broad Panel Cohort is full or the enrollment cap for a tumor type is met.
9.3. 
Populations for Analyses
9.3.1. 
Broad Panel Cohort
The alterations eligible for inclusion in the Broad Panel Cohort consist of target FGFR mutations
and any FGFR fusion. The List of Target FGFR Mutations eligible for the Broad Panel Cohort is
provided in Section 10.11. The Broad Panel Cohort will represent the primary cohort of interest
for analysis. Populations for analysis of the Broad Panel Cohort are specified below:
 
The Treated Population will consist of all subjects (FGFR+) who receive at least 1 dose of
study drug. The Treated Population is the primary population for efficacy and safety analyses.
 
The Response-evaluable Population will include all subjects (FGFR+) who satisfy the
following criteria:
 
Met all eligibility criteria for the study;
 
Received at least 1 dose of study drug;
CCI

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
92
Status: Approved, Date: 22 February 2023
 
Had a baseline and at least 1 adequate post-treatment radiological disease evaluation, or
had clinical signs or symptoms of disease progression, or died prior to the first
posttreatment disease evaluation (these subjects will be considered non-responders).
Adequate disease assessment is defined as having enough evidence to indicate that
progression has or has not occurred.
 
The Core Panel Cohort, which is a subgroup of the Treated Population in the Broad Panel
Cohort with a selected panel of pre-specified FGFR markers, will be assessed as part of the
final analysis. The subset of FGFR markers was selected based on observed clinical activity
in previous studies or a high level of recurrence of these alterations across tumor histologies;
the subset of FGFR markers is outlined below:
 
FGFR3 mutations: S249C; Y373C; R248C; G370C
 
FGFR2 mutation: C382R
 
FGFR3 fusion: FGFR3-TACC3
 
FGFR2 fusions: FGFR2-BICC1; FGFR2-TACC2
The Treated Population will be used to summarize the study population and characteristics,
efficacy, and PRO data; the efficacy and safety analyses will be conducted in the Treated
Population in the Broad Panel Cohort and the Core Panel Cohort. The Response-evaluable
Population will be used for the interim analysis, and supplementary efficacy analysis on key
endpoints such as ORR and DOR.
9.3.2. 
Exploratory Cohort
Subjects enrolled in Exploratory Cohort who receive at least 1 dose of study drug, will be evaluated
for efficacy and safety as the exploratory analysis.
9.3.3. 
Cholangiocarcinoma Expansion Cohort
Subjects enrolled in Cholangiocarcinoma Expansion Cohort with target FGFR mutations or any
FGFR fusion who receive at least 1 dose of study drug, will be evaluated for efficacy and safety
as a separate analysis. The Cholangiocarcinoma Expansion Cohort will be evaluated separately
from the Broad Panel Cohort.
9.3.4. 
Pediatric Cohort
Subjects in the Pediatric Cohort with locally advanced or metastatic solid tumors harboring FGFR
mutations, any gene fusions or FGFR internal tandem duplication who have either progressed
following prior therapies and who have no acceptable standard therapies, or who have a newly
diagnosed solid tumors and who have no acceptable standard therapies, and receive at least 1 dose
of study drug, will be evaluated separately from the Broad Panel Cohort.
9.4. 
Statistical Analyses
9.4.1. 
Primary Endpoint
ORR assessed by IRC: the proportion of subjects who achieve a CR or PR based on RECIST v1.1
or RANO as assessed by IRC.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
93
Status: Approved, Date: 22 February 2023
9.4.2. 
Secondary Efficacy Endpoints
 
ORR assessed by investigator: the proportion of subjects who achieve a CR or PR based on
RECIST v1.1 or RANO as assessed by investigator.
 
DOR: the duration from the date of initial documentation of a response to the date of first
documented evidence of progressive disease (or relapse for subjects who experience CR
during the study), or death, whichever comes first, for subjects. Data from subjects who are
progression-free and alive or have unknown status will be censored at the last tumor
assessment
 
DCR: the proportion of subjects with CR, PR or SD
 
CBR: the proportion of subjects with CR, PR or durable SD (defined as a duration of at least
4 months)
 
PFS: the duration from the date of the first dose of study drug until the date of first documented
evidence of progressive disease (or relapse for subjects who experience CR during the study)
or death, whichever comes first, for subjects. Data from subjects who are progression-free and
alive or have unknown status will be censored at the last tumor assessment
 
OS: measured from the date of first dose of study drug to the date of the subject’s death. If the
subject is alive or the vital status is unknown, the subject’s data will be censored at the date
the subject was last known to be alive
Details for the PRO endpoints will be provided in a separate Statistical Analysis Plan.
9.4.3. 
Efficacy Analyses
9.4.3.1. 
Primary Analysis
The primary analysis for the Broad Panel Cohort will be conducted approximately 6 months after
the first dose of the last Broad Panel Cohort subject (reaching approximately 200
response-evaluable subjects) and the analysis will be based on Treated Population in the Broad
Panel Cohort.
The primary efficacy analysis will be performed on the pooled data of all tumor histologies that
did not meet the futility for the Treated Population in the Broad Panel Cohort and the Core Panel
Cohort. The primary endpoint ORR (CR or PR) according to RECIST v1.1 or RANO criteria
assessed by the IRC will be calculated with 95% 2-sided exact CI. Statistical inference on ORR
by IRC will be tested at 0.025 one-sided level, unless otherwise specified. To adjust for
multiplicity, an error-spending function approach (Spiessens 2010) will be used to split the
significance level using the observed size of the Core Panel Cohort relative to the size of the Broad
Panel Cohort.
Refer to the SAP for details of the supplementary and sensitivity analyses.
Other efficacy analyses that will be focused on the Broad Panel Cohort and the Core Panel Cohort
include:

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
94
Status: Approved, Date: 22 February 2023
 
ORR (CR or PR) according to RECIST v1.1 or RANO criteria assessed by the investigator
will be calculated with 95% 2-sided exact CI
 
The distributions of DOR will be summarized using Kaplan-Meier estimates based on
responding subjects. The estimated median will also be reported along with a 95% CI
 
DCR and CBR will be calculated with 95% 2-sided exact CI
 
PFS and OS will be summarized using similar Kaplan-Meier methods
Safety and efficacy analyses will be conducted on the Cholangiocarcinoma Expansion Cohort and
the Exploratory Cohort at the same time as the primary analysis of the Broad Panel Cohort.
Primary Analysis for the Pediatric Cohort
The treated subjects (approximately 20) who have either progressed following prior therapies and
who have no acceptable standard therapies in the proposed Pediatric Cohort (including the
adolescent subjects enrolled in the Broad Panel Cohort) will be the primary analysis population
for the Pediatric Cohort. The additional approximately 6 subjects who have a newly diagnosed
solid tumors and who have no acceptable standard therapies will be analyzed separately from the
Broad Panel Cohort.
The Pediatric Cohort will have the same primary and secondary endpoints as the Broad Panel
Cohort. In general, all interval estimation will be reported using 2-sided 95% CIs. Disease
progression and response will be primarily based on IRC assessment and secondly based on
investigator assessment, using RECIST v1.1. or RANO criteria. The ORR and its 2-sided 95%
Clopper-Pearson CI will be provided. For time-to-event variables, Kaplan-Meier estimates will be
provided.
9.4.3.2. 
Final Analysis
The final analysis will be performed for all cohorts when the end of data collection timepoint
(defined in Section 5.5) is reached for all cohorts. All efficacy and safety analyses will be updated.
9.4.4. 
Pharmacokinetic and Pharmacodynamic Analyses
Pharmacokinetic data will be summarized and listed for all subjects with available plasma and
CSF erdafitinib concentrations. Additionally, the erdafitinib CSF-to-plasma concentration ratios
will be calculated with CSF and plasma PK samples collected in pair, if the sample collections of
PK plasma samples and PK CSF are within 2 hours of each other. The CSF-to-plasma
concentration ratios will be summarized and listed.
In addition, for children and adolescents only, the following PK parameters will be derived after
serial PK sampling at Cycle 3 Day 1: Cmax, tmax, AUC0-24h, CL/F.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
95
Status: Approved, Date: 22 February 2023
Cmax  
maximum observed analyte concentration
tmax  
the actual sampling time to reach the maximum observed analyte concentration
AUC  
0-24h  
AUC from time of dose to 24h  
a post-dose
CL/F  
total apparent clearance
aThe predose (Cmin) sample at Cycle 4 Day 1 or other cycles in which erdafitinib has reached steady-state can be
used as surrogate for 24-hour postdose PK to derive AUC0-24.
An interim Bayesian population PK and, if appropriate, noncompartmental analysis of plasma
concentration-time data of erdafitinib and markers of pharmacological activities (serum
phosphate) will be performed after 5 children or adolescents (<18 years of age) are enrolled and
have completed Cycle 3 Day 1 in the study. Assessment of the accuracy of the existing population
PK/PD model and model parameters to predict the pediatric population PK and PK serum
phosphate relation will be performed to justify or, ifneeded, update the age guided dose selection
and phosphate guided dose titration of children and adolescent subjects.
Subjects will be excluded from the PK analysis if their data do not allow for accurate assessment
of the PK (eg, missing information of dosing and sampling times; concentration data not sufficient
for PK parameter calculation). All concentrations below the lowest quantifiable concentration or
missing data will be labeled as such in the concentration database. All subjects and samples
excluded from the analysis will be clearly documented in the study report.
Population PK analysis of plasma concentration-time data of erdafitinib may be performed using
nonlinear mixed-effect modeling. Previously developed PK models may be used and updated as
considered appropriate. Relationships between plasma concentrations or metrics of systemic
exposure and CYP2C9 polymorphism, markers of pharmacological activities (serum phosphate),
efficacy or treatment-emergent adverse events may also be explored as data allow using population
approaches. If relevant, results of the analyses will be provided in a separate report.
9.4.5. 
Biomarker Analyses
Changes in molecular markers (FGFR or other genes), disease relevant biomarkers, and phosphate
levels over time will be summarized by treatment group. Associations between baseline levels and
changes from baseline in select markers and clinical response will be explored.
Results of exploratory biomarker analyses may be presented in a separate report. Planned
biomarker analyses may be deferred if emerging study data show no likelihood of providing useful
scientific information.
9.4.6. 
Medical Resource Utilization and Patient-reported Outcomes
Analyses
Medical resource utilization and PRO measures will be summarized descriptively (ie, mean,
standard deviation including change from baseline) at each assessment time point. Additional
analyses may be conducted; details and results of any additional analyses will be presented in a
separate report.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
96
Status: Approved, Date: 22 February 2023
9.4.7. 
Safety Analyses
Adverse Events
The verbatim terms used in the CRF by investigators to identify adverse events will be coded using
the Medical Dictionary for Regulatory Activities (MedDRA). Treatment-emergent adverse events
are adverse events with onset during the Treatment Phase or that are a consequence of a
pre-existing condition that has worsened since baseline. All reported treatment-emergent adverse
events will be included in the analysis. For each adverse event, the percentage of subjects who
experience at least 1 occurrence of the given event will be summarized by intervention group. In
addition, comparisons between intervention groups will be provided if appropriate.
Summaries, listings, datasets, or subject narratives may be provided, as appropriate, for those
subjects who die, who discontinue intervention due to an adverse event, or who experience a severe
or a serious adverse event.
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test. Reference ranges and markedly
abnormal results (specified in the Statistical Analysis Plan) will be used in the summary of
laboratory data. Descriptive statistics will be calculated for each laboratory analyte at baseline and
at each scheduled time point. Changes from baseline results will be presented in pre- versus
post-intervention cross-tabulations (with classes for below, within, and above normal ranges).
Frequency tabulations of the abnormalities will be made. A listing of subjects with any laboratory
results outside the reference ranges will be provided. A listing of subjects with any markedly
abnormal laboratory results will also be provided. Parameters with predefined NCI-CTCAE
toxicity grades will be summarized. Change from baseline to the worst adverse event grade
experienced by the subject during the study will be provided as shift tables.
Electrocardiogram
Electrocardiogram data will be summarized by ECG parameter. Descriptive statistics will be
calculated at baseline and for observed values and changes from baseline at each scheduled time
point. Frequency tabulations of the abnormalities will be made.
The ECG variables that will be analyzed are heart rate, PR interval, QRS interval, QT interval, and
QT corrected according to Fridericia's formula (QTcF). The Bazett formula may be used for
children and adolescent subjects. Descriptive statistics of QTc intervals and changes from baseline
will be summarized at each scheduled time point. The percentage of subjects with QTc interval
>450 milliseconds, >480 milliseconds, or >500 milliseconds will be summarized, as will the
percentage of subjects with QTc interval increases from baseline >30 milliseconds or
>60 milliseconds. All clinically relevant abnormalities in ECG waveform that are changes from
the baseline readings will be reported (eg, changes in T-wave morphology or the occurrence of
U-waves).

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
97
Status: Approved, Date: 22 February 2023
ECOG
ECOG grade will be summarized at each scheduled time point. Descriptive statistics will be
calculated at baseline and for observed values and changes from baseline at each scheduled time
point.
Bone-related Assessments
Descriptive statistics will be calculated at baseline and for observed values and changes from
baseline at each scheduled time point.
9.5. 
Interim Analyses
Broad Panel Cohort
Three interim futility analyses are planned for the Broad Panel Cohort when 30%, 50%, and 70%
of the subjects (ie, approximately 60, 100, and 140 subjects) have been treated and are considered
response-evaluable by investigator assessment, irrespective of the tumor histologies and the
distribution among the tumor histologies (Figure 7, N represents the number of response-evaluable
subjects). The tumor histology list for futility analysis is pre-defined in Table 16 (except for the
group Other including all other tumor histologies not listed). In addition, an interim efficacy
analysis will be conducted for the Broad Panel Cohort after 50% subjects being treated and
considered response-evaluable (at the same time as the second interim futility analysis, Figure 7).
An early success may be declared if the observed ORR is 50% or higher, with consistent effect
across histologies and few tumor histologies were stopped (ie, for enrollment) due to the futility
analyses. Regardless of the outcome of the interim efficacy analysis, study enrollment will
continue to better characterize the efficacy for active tumor histologies. The results of the interim
analyses will be reviewed by the DRC.
The interim futility analyses will be based on the ORR assessed by investigator using a Bayesian
hierarchical model (BHM), implemented in FACTS v6.2 Enrichment Design – Dichotomous
(Berry 2013, Chugh 2009). The BHM borrows information across tumor histologies and allows
for evaluation of each tumor histology individually given the often-unique features of each group.
At least 5 subjects in a tumor histology are required for the futility analysis for the given tumor
histology. The futility criteria will be met if the posterior probability (ORR >25%) is <40% in the
Broad Panel Cohort for a given tumor histology. More details are in the Appendix to the draft
Statistical Analysis Plan provided with this submission. All available data (eg, efficacy, safety,
and biomarker data) will be assessed to determine whether enrollment in a given tumor histology
should continue, including the representativeness of biomarker alterations (the expected variant
representation by tumor histology based on genomic database assessment). If a tumor histology is
deemed futile by the DRC, further enrollment in the group will stop; subjects who have been
enrolled in the tumor histology group will continue treatment and evaluation as per the protocol.
Details of the composition of the DRC and the operational procedures will be specified in the DRC
charter.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
99
Status: Approved, Date: 22 February 2023
have completed Cycle 3 Day 1 in the study (see Section 9.4.4). In addition, further interim analyses
may be conducted after enrollment of additional subjects.
9.6. 
Data Review Committee
A DRC will be established as noted in Committees Structure in Section 10.3, Regulatory, Ethical,
and Study Oversight Considerations.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
100
Status: Approved, Date: 22 February 2023
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Abbreviations
α1-AGP  
α1-acid glycoprotein
ADL 
activities of daily living
AE 
adverse event
ALT  
alanine aminotransferase
ANC  
absolute neutrophil count
AP  
anteroposterior
AST  
aspartate aminotransferase
AUC  
area under the curve
β-hCG  
beta-human chorionic gonadotropin
BPC 
Broad Panel Cohort
BSA 
body surface area
CBR  
clinical benefit rate
CI 
confidence interval
CLIA  
Clinical Laboratory Improvement Amendments
Cmax  
maximum plasma drug concentration
CNS  
central nervous system
CNV  
copy number variation
COVID-19 
coronavirus disease 2019
CR  
CRF  
CSF  
complete response
case report form
cerebrospinal fluid
CSR  
CT  
central serous retinopathy
computed tomography
ctDNA  
circulating tumor DNA
CYP  
CXDX  
DCR  
cytochrome P450
Cycle X Day X
disease control rate
DEXA  
dual-energy X-ray absorptiometry
DNA  
deoxyribonucleic acid
DOR  
DRC  
duration of response
Data Review Committee
ECGs 
electrocardiograms
ECOG  
Eastern Cooperative Oncology Group
eCRF  
electronic case report form
eDC  
electronic data capture
EORTC-QLQ-C30 
European Organisation for Research and Treatment of Cancer Quality-of-life
Questionnaire Core 30
EQ-5D-5L 
European Quality of Life –5 Dimensions-5 Levels
EU  
European Union
FGFR  
fibroblast growth factor receptor
GBM  
Glioblastoma multiforme
GCP  
GENIE 
HGG  
HNSCC  
Good Clinical Practice
Genomics Evidence Neoplasia Information Exchange [database]
high grade glioma
head and neck squamous cell carcinoma
HRQoL 
health-related quality of life
ICF  
informed consent form
ICH  
International Council for Harmonisation
IHC  
immunohistochemistry
IEC  
Independent Ethics Committee
INR  
international normalized ratio
IRC  
Independent Review Committee
IRB  
Institutional Review Board

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
101
Status: Approved, Date: 22 February 2023
LTE 
long-term extension
MRI 
magnetic resonance imaging
NCCN  
National Comprehensive Cancer Network
NCI-COG Pediatric 
    MATCH studies 
National Cancer Institute and Children’s Oncology Group Pediatric Molecular Analysis
for Therapy Choice [Substudy for Erdafitinib]
NCI-CTCAE  
NGS  
National Cancer Institute Common Terminology Criteria for Adverse Events
next-generation sequencing
NSCLC  
non-small cell lung cancer
OCT  
optical coherence tomography
ORR  
overall response rate
OS  
overall survival
PA 
posteroanterior
PCC  
protocol clarification communication
PCR  
polymerase chain reaction
PD 
pharmacodynamic(s)
PD-L1 
programmed death-ligand 1
Peds FACT-Br 
Pediatric Functional Assessment Of Cancer Therapy - Brain
PFS  
progression-free survival
PGIC  
Patient Global Impression of Change
PGIS  
Patient Global Impression of Symptom Severity
P-gp 
P-glycoprotein
PK 
pharmacokinetic(s)
PQC  
Product Quality Complaint
PR 
partial response
PRO  
PTH  
Patient-reported Outcome
parathyroid hormone
RANO  
Response Assessment in Neuro-Oncology
RECIST 
Response Evaluation Criteria in Solid Tumors
RNA  
ribonucleic acid
RPED  
retinal pigment epithelial detachment
RT-PCR  
reverse transcription polymerase chain reaction
RVO  
retinal vein occlusion
SCFE 
slipped capital femoral epiphysis
SD 
stable disease
TCGA  
The Cancer Genome Atlas [database]
ULN  
US  
upper limit of normal
United States
VAS  
visual analog scale

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
102
Status: Approved, Date: 22 February 2023
10.2. Appendix 2: Clinical Laboratory Tests
Blood samples for serum chemistry and hematology will be collected according to the Schedule
of Activities. More frequent clinical laboratory tests may be performed, as indicated by the overall
clinical condition of the subject and for abnormalities that warrant more frequent monitoring.
The investigator must review the laboratory report, document this review, and record any clinically
relevant changes occurring during the study in the adverse event section of the eCRF.
The following tests will be performed by the local laboratory:
Hematology Panel
-hemoglobin
-platelet count
-white blood cell (WBC) count and absolute neutrophil count (ANC) only
Serum Chemistry Panel
-alanine aminotransferase (ALT) 
-calcium
-aspartate aminotransferase (AST) 
-phosphate
-total bilirubin  
-potassium
-chloride 
-sodium
-bicarbonate (if feasible) 
-magnesium
-creatinine (including calculated 
creatinine clearance) 
-alkaline phosphatase
-albumin
Possible Hy’s Law case reporting requirements are defined in Section 8.4.1
Parathyroid hormone
Thyroid hormones (children and adolescents only)
- Thyroid stimulating hormone (TSH), free thyroxine (T4), and total triiodothyronine (T3)
Insulin-like growth factor 1 (IGF-1) (children and adolescents only)
Creatinine or creatinine clearance will be determined per institutional standard.
A urine or serum sample will be obtained for a pregnancy test (β-hCG) in sexually active female
subjects of childbearing potential at screening within 7 days of the first dose, or at Cycle 1 Day 1
prior to the first dose, and at End-of-Treatment. Additional serum or urine pregnancy tests will be
performed on Day 1 of every cycle (starting with Cycle 2 Day 1), to establish the absence of
pregnancy at any time during the subject's participation in the study.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
103
Status: Approved, Date: 22 February 2023
10.3. Appendix 3: Regulatory, Ethical, and Study Oversight Considerations
10.3.1. 
Regulatory and Ethical Considerations
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current International Council for Harmonisation (ICH) guidelines on Good Clinical
Practice (GCP), and applicable regulatory and country/territory-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing,
conducting, recording, and reporting studies that involve the participation of human subjects.
Compliance with this standard provides public assurance that the rights, safety, and well-being of
study subjects are protected, consistent with the principles that originated in the Declaration of
Helsinki, and that the study data are credible.
Protocol Clarification Communications
If text within a final approved protocol requires clarification (eg, current wording is unclear or
ambiguous) that does not change any aspect of the current study conduct, a protocol clarification
communication (PCC) may be prepared. The PCC Document will be communicated to the
Investigational Site, Site Monitors, Local Trial Managers, Clinical Trial Managers, and/or Contract
Research Organizations who will ensure that the PCC explanations are followed by the
investigators.
The PCC Document may be shared by the sites with IECs/IRBs per local regulations.
The PCC Documents must NOT be used in place of protocol amendments, but the content of the
PCC Document must be included in any future protocol amendments.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment by
the sponsor. All protocol amendments must be issued by the sponsor and signed and dated by the
investigator. Protocol amendments must not be implemented without prior IEC/IRB approval, or
when the relevant competent authority has raised any grounds for non-acceptance, except when
necessary to eliminate immediate hazards to the subjects, in which case the amendment must be
promptly submitted to the IEC/IRB and relevant competent authority. Documentation of
amendment approval by the investigator and IEC/IRB must be provided to the sponsor. When the
change(s) involve only logistic or administrative aspects of the study, the IEC/IRB (where
required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable,
the investigator or other physician in attendance will contact the appropriate sponsor representative
listed in the Contact Information page(s), which will be provided as a separate document. Except
in emergency situations, this contact should be made before implementing any departure from the
protocol. In all cases, contact with the sponsor must be made as soon as possible to discuss the

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
104
Status: Approved, Date: 22 February 2023
situation and agree on an appropriate course of action. The data recorded in the CRF and source
documents will reflect any departure from the protocol, and the source documents will describe
this departure and the circumstances requiring it.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities
in each respective country/territory, if applicable. A study may not be initiated until all local
regulatory requirements are met.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study drug to the
study site:
 
Protocol and amendment(s), if any, signed and dated by the principal investigator
 
A copy of the dated and signed (or sealed, where appropriate per local regulations), written
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if
applicable, subject compensation programs. This approval must clearly identify the specific
protocol by title and number and must be signed (or sealed, where appropriate per local
regulations) by the chairman or authorized designee.
 
Name and address of the IEC/IRB, including a current list of the IEC/IRB members and their
function, with a statement that it is organized and operates according to GCP and the
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, from
the IEC/IRB, a general statement may be substituted for this list. If an investigator or a
member of the study-site personnel is a member of the IEC/IRB, documentation must be
obtained to state that this person did not participate in the deliberations or in the vote/opinion
of the study.
 
Regulatory authority approval or notification, if applicable
 
Signed and dated statement of investigator (eg, Form FDA 1572), if applicable
 
Documentation of investigator qualifications (eg, curriculum vitae)
 
Completed investigator financial disclosure form from the principal investigator, where
required
 
Signed and dated clinical trial agreement, which includes the financial agreement
 
Any other documentation required by local regulations
The following documents must be provided to the sponsor before enrollment of the first subject:
 
Completed investigator financial disclosure forms from all subinvestigators
 
Documentation of subinvestigator qualifications (eg, curriculum vitae)
 
Name and address of any local laboratory conducting tests for the study, and a dated copy of
current laboratory normal ranges for these tests, if applicable

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
105
Status: Approved, Date: 22 February 2023
 
Local laboratory documentation demonstrating competence and test reliability
(eg, accreditation/license), if applicable
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the IEC/IRB
with current and complete copies of the following documents (as required by local regulations):
 
Final protocol and, if applicable, amendments
 
Sponsor-approved ICF (and any other written materials to be provided to the subjects)
 
IB (or equivalent information) and amendments/addenda
 
Sponsor-approved subject recruiting materials
 
Information on compensation for study-related injuries or payment to subjects for
participation in the study, if applicable
 
Investigator's curriculum vitae or equivalent information (unless not required, as documented
by the IEC/IRB)
 
Information regarding funding, name of the sponsor, institutional affiliations, other potential
conflicts of interest, and incentives for subjects
 
Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final protocol,
amendments (if any, excluding the ones that are purely administrative, with no consequences for
subjects, data or study conduct, unless required locally), the ICF, applicable recruiting materials,
and subject compensation programs, and the sponsor has received a copy of this approval. This
approval letter must be dated and must clearly identify the IEC/IRB and the documents being
approved.
During the study, the investigator (or sponsor where required) will send the following documents
and updates to the IEC/IRB for their review and approval, where appropriate:
 
Protocol amendments (excluding the ones that are purely administrative, with no
consequences for subjects, data or study conduct)
 
Revision(s) to ICF and any other written materials to be provided to subjects
 
If applicable, new or revised subject recruiting materials approved by the sponsor
 
Revisions to compensation for study-related injuries or payment to subjects for participation
in the study, ifapplicable
 
New edition(s) of the Investigator Brochure and amendments/addenda
 
Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at
least annually)
 
Reports of adverse events that are serious, unlisted/unexpected, and associated with the study
drug

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
106
Status: Approved, Date: 22 February 2023
 
New information that may adversely affect the safety of the subjects or the conduct of the
study
 
Deviations from or changes to the protocol to eliminate immediate hazards to the subjects
 
Report of deaths of subjects under the investigator's care
 
Notification if a new investigator is responsible for the study at the site
 
Development Safety Update Report and Line Listings, where applicable
 
Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no
consequences for subjects, data or study conduct), the amendment and applicable ICF revisions
must be submitted promptly to the IEC/IRB for review and approval before implementation of the
change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about
the study completion.
Long-Term Extension and Post-trial Access
Once the end of data collection timepoint (see Section 5.5) has been achieved, follow-up of
subjects will end, and data collection will conclude. Subjects in the Treatment Phase who are
continuing to derive benefit from study treatment as determined by their investigator may continue
to receive access to study treatment either on this study, with onlydata collectionof serious adverse
events in the company safety repository  (see Section 5.5 and Error! Reference source not
found.) via LTE phase or a post-trial access program, when permitted by local regulations.
Provision may continue until the subject can commercially access study treatment within the local
healthcare system, until a decision is made not to pursue the studied indication, until the
investigator decides it is in the best interest of the subject that study treatment be discontinued, or
until 2 years after local marketing authorization is obtained for the studied indication, whichever
comes first.
Country/Territory Selection
This study will only be conducted in those countries/territories where the intent is to launch or
otherwise help ensure access to the developed product if the need for the product persists, unless
explicitly addressed as a specific ethical consideration in Section 4.2.4, Study-Specific Ethical
Design Considerations.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.4.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
107
Status: Approved, Date: 22 February 2023
10.3.2. 
Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial
information in accordance with local regulations to allow the sponsor to submit complete and
accurate financial certification or disclosure statements to the appropriate regulatory authorities.
Investigators are responsible for providing information on financial interests during the course of
the study and for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above) for details on financial disclosure.
10.3.3. 
Informed Consent Process and Assent Form
Each subject (or a legally acceptable representative) must give written consent according to local
requirements after the nature, significance, and purpose of the study, and procedures required for
the study, and consequence of the study, have been fully explained. The ICF(s) must be signed
before performance of any study-related activity. The ICF(s) and assent form that is/are used must
be approved by both the sponsor and by the reviewing IEC/IRB and be in a language that the
subject can read and understand. The informed consent should be in accordance with principles
that originated in the Declaration of Helsinki, current ICH and GCP guidelines, applicable
regulatory requirements, and sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study-site
personnel must explain to potential subjects or their legally acceptable representatives the aims,
methods, reasonably anticipated benefits, and potential hazards of the study, and any discomfort
participation in the study may entail. Subjects will be informed that their participation is voluntary
and that they may withdraw consent to participate at any time. They will be informed that choosing
not to participate will not affect the care the subject will receive for the treatment of his or her
disease. Subjects will be told that alternative treatments are available if they refuse to take part and
that such refusal will not prejudice future treatment. Finally, they will be told that the investigator
will maintain a subject identification register for the purposes of long-term follow up if needed
and that their records may be accessed by health authorities and authorized sponsor personnel
without violating the confidentiality of the subject, to the extent permitted by the applicable law(s)
or regulations. By signing the ICF the subject or legally acceptable representative is authorizing
such access, which includes permission to obtain information about his or her survival status. It
also denotes that the subject agrees to allow his or her study physician to recontact the subject for
the purpose of obtaining consent for additional safety evaluations, and subsequent disease-related
treatments, if needed.
The subject or legally acceptable representative will be given sufficient time to read the ICF and
the opportunity to ask questions. After this explanation and before entry into the study, consent
should be appropriately recorded by means of either the subject's or his or her legally acceptable
representative's personally dated signature. After having obtained the consent, a copy of the ICF
must be given to the subject.
If the subject or legally acceptable representative is unable to read or write, an impartial witness
should be present for the entire informed consent process (which includes reading and explaining

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
108
Status: Approved, Date: 22 February 2023
all written information) and should personally date and sign the ICF after the oral consent of the
subject or legally acceptable representative is obtained.
Children (minors) or subjects who are unable to comprehend the information provided can be
enrolled only after obtaining consent of a legally acceptable representative. Assent must be
obtained from children (minors) capable of understanding the nature of the study, typically subjects
7 years of age and older, depending on the institutional policies; children ≥6 to <12 years of age,
adolescents 12 years of age and above and adults will be enrolled in this study. WrittenAssent should
be obtained from subjects who are able to write. A separate assent form written in language the
subject can understand should be developed for children and adolescents. After having obtained
the assent, a copy of the assent form must be given to the subject, and to the subject's parent(s) or
if applicable legally acceptable representative. Minors who reach the age of majority (per local
regulations) during study will need to (re)sign an ICF.
When prior consent of the subject is not possible and the subject's legally acceptable representative
is not available, enrollment procedures should be described in the protocol with documented
approval/favorable opinion by the IEC/IRB to protect the rights, safety, and well-being of the
subject and to ensure compliance with applicable regulatory requirements. The subject or legally
acceptable representative must be informed about the study as soon as possible and give consent
to continue.
10.3.4. 
Data Protection
Privacy of Personal Data
The collection and processing of personal data from subjects enrolled in this study will be limited
to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality
and compliance with applicable data privacy protection laws and regulations. Appropriate
technical and organizational measures to protect the personal data against unauthorized disclosures
or access, accidental or unlawful destruction, or accidental loss or alteration must be put in place.
Sponsor personnel whose responsibilities require access to personal data agree to keep the identity
of subjects confidential.
The informed consent obtained from the subject (or his or her legally acceptable representative)
includes information about, and where required per applicable regulations, explicit consent for the
processing of personal data and for the investigator/institution to allow direct access to his or her
original medical records (source data/documents) for study-related monitoring, audit, IEC/IRB
review, and regulatory inspection. The informed consent also provides information to address the
lawful transfer of the data to other entities and to other countries/territories.
The subject has the right to request through the investigator access to his or her personal data and
the right to request rectification of any data that are not correct or complete, or make requests
concerning his or her personal data in accordance with applicable data protection law. Reasonable

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
109
Status: Approved, Date: 22 February 2023
steps will be taken to respond to such a request, taking into consideration the nature of the request,
the conditions of the study, and the applicable laws and regulations.
In the event of a data security breach, the sponsor will apply measures to adequately manage and
mitigate possible adverse effects taking into consideration the nature of the data security breach as
necessary to address other obligations such as notifying appropriate authorities in accordance with
applicable data protection law.
Exploratory biomarker and PK research is not conducted under standards appropriate for the return
of data to subjects. In addition, the sponsor cannot make decisions as to the significance of any
findings resulting from exploratory research. Therefore, exploratory research data will not be
returned to subjects or investigators, unless required by law or local regulations. Privacy and
confidentiality of data generated in the future on stored samples will be protected by the same
standards applicable to all other clinical data.
10.3.5. 
Long-Term Retention of Samples for Additional Future Research
Samples collected in this study may be stored for up to 15 years (or according to local regulations)
for additional research. Samples will only be used to understand erdafitinib, to understand
advanced solid tumors with FGFR aberrations, to understand differential intervention responders,
and to develop tests/assays related to erdafitinib and advanced solid tumors with FGFR
aberrations. The research may begin at any time during the study or the post-study storage period.
Stored samples will be coded throughout the sample storage and analysis process and will not be
labeled with personal identifiers. Subjects may withdraw their consent for their samples to be
stored for research (refer to Section 7.2.1, Withdrawal From the Use of Research Samples).
10.3.6. 
Committee Structure
Data Review Committee
A DRC will be established for review of safety data and for monitoring of interim efficacy data,
to ensure the continuing safety of the subjects enrolled in this study and to meet efficacy objectives.
This committee will consist of at least one medical expert in the relevant therapeutic area and at
least one statistician; committee membership responsibilities, authorities, and procedures will be
documented in its charter. The committee will meet periodically to review interim data including
safety data. After the review, the DRC will make recommendations regarding the continuation of
enrollment in each histology or the continuation of the study. The DRC will also determine whether
to enroll more subjects into a tumor histology when the prespecified cap of approximately
30 subjects is reached. Details of the composition of the DRC and their operational procedures
will be specified in the DRC Charter.
10.3.7. 
Publication Policy/Dissemination of Clinical Study Data
All information, including but not limited to information regarding erdafitinib or the sponsor's
operations (eg, patent application, formulas, manufacturing processes, basic scientific data, prior
clinical data, formulation information) supplied by the sponsor to the investigator and not

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
110
Status: Approved, Date: 22 February 2023
previously published, and any data, including exploratory PK or biomarker research data,
generated as a result of this study, are considered confidential and remain the sole property of the
sponsor. The investigator agrees to maintain this information in confidence and use this
information only to accomplish this study and will not use it for other purposes without the
sponsor's prior written consent.
The investigator understands that the information developed in the study will be used by the
sponsor in connection with the continued development of erdafitinib, and thus may be disclosed
as required to other clinical investigators or regulatory agencies. To permit the information derived
from the clinical studies to be used, the investigator is obligated to provide the sponsor with all
data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the sponsor and
will contain data from all study sites that participated in the study as per protocol. Recruitment
performance or specific expertise related to the nature and the key assessment parameters of the
study will be used to determine a coordinating investigator for the study. Results of exploratory
PK or biomarker analyses performed after the Clinical Study Report has been issued will be
reported in a separate report and will not require a revision of the Clinical Study Report.
Study subject identifiers will not be used in publication of results. Any work created in connection
with performance of the study and contained in the data that can benefit from copyright protection
(except any publication by the investigator as provided for below) shall be the property of the
sponsor as author and owner of copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal
Editors (ICMJE) guidelines, the sponsor shall have the right to publish such primary (multicenter)
data and information without approval from the investigator. The investigator has the right to
publish study site-specific data after the primary data are published. If an investigator wishes to
publish information from the study, a copy of the manuscript must be provided to the sponsor for
review at least 60 days before submission for publication or presentation. Expedited reviews will
be arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in
writing, the investigator will withhold such publication for up to an additional 60 days to allow for
filing of a patent application. In the event that issues arise regarding scientific integrity or
regulatory compliance, the sponsor will review these issues with the investigator. The sponsor will
not mandate modifications to scientific content and does not have the right to suppress information.
For multicenter study designs and sub-study approaches, secondary results generally should not
be published before the primary endpoints of a study have been published. Similarly, investigators
will recognize the integrity of a multicenter study by not submitting for publication data derived
from the individual study site until the combined results from the completed study have been
submitted for publication, within 18 months after the study end date, or the sponsor confirms there
will be no multicenter study publication. Authorship of publications resulting from this study will
be based on the guidelines on authorship, such as those described in the ICMJE Recommendations
for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals, which
state that the named authors must have made a significant contribution to the conception or design

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
111
Status: Approved, Date: 22 February 2023
of the work; or the acquisition, analysis, or interpretation of the data for the work; and drafted the
work or revised it critically for important intellectual content; and given final approval of the
version to be published; and agreed to be accountable for all aspects of the work in ensuring that
questions related to the accuracy or integrity of any part of the work are appropriately investigated
and resolved.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required
by law. The disclosure of the final study results will be performed after the end of study in order
to ensure the statistical analyses are relevant.
10.3.8. 
Data Quality Assurance
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified
investigators and appropriate study sites, review of protocol procedures with the investigator and
study-site personnel before the study, and periodic monitoring visits by the sponsor. Written
instructions will be provided for collection, handling, storage, and shipment of samples.
Guidelines for CRF completion will be provided and reviewed with study-site personnel before
the start of the study. The sponsor will review CRF for accuracy and completeness during on-site
monitoring visits and after transmission to the sponsor; any discrepancies will be resolved with the
investigator or designee, as appropriate. After upload of the data into the study database they will
be verified for accuracy and consistency with the data sources.
10.3.9. 
Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each subject in electronic format.
All data relating to the study must be recorded in CRF. All CRF entries, corrections, and alterations
must be made by the investigator or authorized study-site personnel. The investigator must verify
that all data entries in the CRF are accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an
electronic CRF, if applicable. Study-specific data will be transmitted in a secure manner to the
sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the CRF. Any
such worksheets will become part of the subject's source documents. Data must be entered into
CRF in English. The CRF must be completed as soon as possible after a subject visit and the forms
should be available for review at the next scheduled monitoring visit.
All participative measurements (eg, pain scale information or other questionnaires) will be
completed by the same individual who made the initial baseline determinations whenever possible.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
112
Status: Approved, Date: 22 February 2023
If necessary, queries will be generated in the eDC tool. If corrections to a CRF are needed after
the initial entry into the CRF, this can be done in either of the following ways:
 Investigator and study-site personnel can make corrections in the eDC tool at their own
initiative or as a response to an auto query (generated by the eDC tool).
 Sponsor or sponsor delegate can generate a query for resolution by the investigator and
study-site personnel.
10.3.10. 
Source Documents
At a minimum, source documents consistent in the type and level of detail with that commonly
recorded at the study site as a basis for standard medical care must be available for the following:
subject identification, eligibility, and study identification; study discussion and date of signed
informed consent; dates of visits; results of safety and efficacy parameters as required by the
protocol; record of all adverse events and follow-up of adverse events; concomitant medication;
intervention receipt/dispensing/return records; study drug administration information; and date of
study completion and reason for early discontinuation of study drug or withdrawal from the study,
if applicable.
The author of an entry in the source documents should be identifiable.
Specific details required as source data for the study and source data collection methods will be
reviewed with the investigator before the study and will be described in the monitoring guidelines
(or other equivalent document). Missing PRO data form will be recorded directly into the CRF
and will be considered as source data.
The minimum source documentation requirements for Section 5.1, Inclusion Criteria and
Section 5.2, Exclusion Criteria that specify a need for documented medical history are as follows:
 Referral letter from treating physician or
 Complete history of medical notes at the site
 Discharge summaries
Inclusion and exclusion criteria not requiring documented medical history must be verified at a
minimum by subject interview or other protocol required assessment (eg, physical examination,
laboratory assessment) and documented in the source documents.
An eSource system may be utilized, which contains data traditionally maintained in a hospital or
clinic record to document medical care (eg, electronic source documents) as well as the clinical
study-specific data fields as determined by the protocol. This data is electronically extracted for
use by the sponsor. If eSource is utilized, references made to the CRF in the protocol include the
eSource system, but information collected through eSource may not be limited to that found in the
CRF.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
113
Status: Approved, Date: 22 February 2023
10.3.11. 
Monitoring
The sponsor will use a combination of monitoring techniques (central, remote, or on-site
monitoring) to monitor this study.
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will
record dates of the visits in a study site visit log that will be kept at the study site. The first
post-initiation visit will be made as soon as possible after enrollment has begun. At these visits,
the monitor will compare the data entered into the CRF with the source documents
(eg, hospital/clinic/physician’s office medical records). The nature and location of all source
documents will be identified to ensure that all sources of original data required to complete the
CRF are known to the sponsor and study-site personnel and are accessible for verification by the
sponsor study-site contact. If electronic records are maintained at the study site, the method of
verification must be discussed with the study-site personnel.
Direct access to source documents (medical records) must be allowed for the purpose of verifying
that the recorded data are consistent with the original source data. Findings from this review will
be discussed with the study-site personnel. The sponsor expects that, during monitoring visits, the
relevant study-site personnel will be available, the source documents will be accessible, and a
suitable environment will be provided for review of study-related documents. The monitor will
meet with the investigator on a regular basis during the study to provide feedback on the study
conduct.
10.3.12. 
On-site Audits
Representatives of the sponsor's clinical quality assurance department may visit the study site at
any time during or after completion of the study to conduct an audit of the study in compliance
with regulatory guidelines and company policy. These audits will require access to all study
records, including source documents, for inspection. Subject privacy must, however, be respected.
The investigator and study-site personnel are responsible for being present and available for
consultation during routinely scheduled study-site audit visits conducted by the sponsor or its
designees.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as part
of a national GCP compliance program or to review the results of this study in support of a
regulatory submission. The investigator should immediately notify the sponsor if the subject has
been contacted by a regulatory agency concerning an upcoming inspection.
10.3.13. 
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all CRF and
all source documents that support the data collected from each subject, as well as all study
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical
Trial, and all study documents as specified by the applicable regulatory requirement(s). The
investigator/institution will take measures to prevent accidental or premature destruction of these
documents.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
114
Status: Approved, Date: 22 February 2023
Essential documents must be retained until at least 2 years after the last approval of a marketing
application in an ICH region and until there are no pending or contemplated marketing applications
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical
development of the investigational product. These documents will be retained for a longer period
if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the
responsibility of the sponsor to inform the investigator/institution as to when these documents no
longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the
responsibility of keeping the study records, custody must be transferred to a person who will accept
the responsibility. The sponsor must be notified in writing of the name and address of the new
custodian. Under no circumstance shall the investigator relocate or dispose of any study documents
before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any
documentation relating to this study, the investigator/institution must permit access to such reports.
10.3.14. 
Study and Site Start and Closure
First Act of Recruitment
The first site open is considered the first act of recruitment and it becomes the study start date.
Study Termination
The sponsor 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 IEC/IRB or
local health authorities, the sponsor's procedures, or GCP guidelines
 Inadequate recruitment of subjects by the investigator
 Discontinuation of further study drug development

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
115
Status: Approved, Date: 22 February 2023
10.4. Appendix 4: Adverse Events: Definitions and Procedures for Recording,
Evaluating, Follow-up, and Reporting
Method ofDetecting Adverse Events and Serious Adverse Events
Care will be taken not to introduce bias when detecting adverse events or serious adverse events.
Open-ended and nonleading verbal questioning of the subject is the preferred method to inquire
about adverse event occurrence.
Solicited Adverse Events
Solicited adverse events are predefined local and systemic events for which the subject is
specifically questioned.
Unsolicited Adverse Events
Unsolicited adverse events are all adverse events for which the subject is specifically not
questioned.
10.4.1. 
Adverse Event Definitions and Classifications
Adverse Event
An adverse event is any untoward medical occurrence in a clinical study subject administered a
medicinal (investigational or non-investigational) product. An adverse event does not necessarily
have a causal relationship with the intervention. An adverse event can therefore be any unfavorable
and unintended sign (including an abnormal finding), symptom, or disease temporally associated
with the use of a medicinal (investigational or non-investigational) product, whether or not related
to that medicinal (investigational or non-investigational) product. (Definition per ICH)
This includes any occurrence that is new in onset or aggravated in severity or frequency from the
baseline condition, or abnormal results of diagnostic procedures, including laboratory test
abnormalities.
Note: The sponsor collects adverse events starting with the signing of the Full-study ICF (refer to
All Adverse Events under Section 8.4.1, Time Period and Frequency for Collecting Adverse
Events and Serious Adverse Events Information, for time of last adverse event recording).
Serious Adverse Event
A serious adverse event based on ICH and EU Guidelines on Pharmacovigilance for Medicinal
Products for Human Use is any untoward medical occurrence that at any dose:
 
Results in death
 
Is life-threatening
(The subject was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.)
 
Requires inpatient hospitalization or prolongation of existing hospitalization

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
116
Status: Approved, Date: 22 February 2023
 
Results in persistent or significant disability/incapacity
 
Is a congenital anomaly/birth defect
 
Is a suspected transmission of any infectious agent via a medicinal product
 
Is Medically Important*
* Medical and scientific judgment should be exercised in deciding whether expedited reporting is
also appropriate in other situations, such as important medical events that may not be immediately
life threatening or result in death or hospitalization but may jeopardize the subject or may require
intervention to prevent one of the other outcomes listed in the definition above. These should
usually be considered serious.
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An adverse event is considered unlisted if the nature or severity is not consistent with the applicable
product reference safety information. For erdafitinib, the expectedness of an adverse event will be
determined by whether or not it is listed in the IB.
Assessment of Causality
The causal relationship to study treatment is determined by the investigator. The following
selection should be used to assess all AEs.
Related
There is a reasonable causal relationship between study treatment administration and the
AE.
Not related
There is not a reasonable causal relationship between study treatment administration and
the AE.
The term "reasonable causal relationship" means there is evidence to support a causal relationship.
10.4.2. 
Severity Criteria
Adverse event severity is a clinical determination of the intensity of an adverse event. The severity
assessment for an adverse event or serious adverse event should be completed using the
NCI-CTCAE, Version 5 or higher. Any adverse event or serious adverse event not listed in the
NCI-CTCAE, Version 5 or higher will be graded according to the investigator clinical judgment
by using the standard grades as follows:
 Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only;
intervention not indicated.
 Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting
age-appropriate instrumental activities of daily living (ADL)a.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
117
Status: Approved, Date: 22 February 2023
 Grade 3: Severe or medically significant but not immediately life-threatening;
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care
activities of daily livingb.
 Grade 4: Life-threatening consequences; urgent intervention indicated.
 Grade 5: Death related to AE.
a Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the
telephone, managing money, etc.
b Self-care ADL refers to bathing; dressing and undressing; feeding self; using the toilet; taking
medications; and not bedridden.
The investigator should use clinical judgment in assessing the severity of events not directly
experienced by the subject (eg, laboratory abnormalities).
10.4.3. 
Special Reporting Situations
Safety events of interest on a sponsor study drug in an interventional study that may require
expedited reporting or safety evaluation include, but are not limited to:
 
Overdose of a sponsor study drug
 
Suspected abuse/misuse of a sponsor study drug
 
Accidental or occupational exposure to a sponsor study drug
 
Medication error involving a sponsor product (with or without subject/patient exposure to the
sponsor study drug, eg, name confusion)
 
Exposure to a sponsor study drug from breastfeeding
Special reporting situations should be recorded in the CRF. Any special reporting situation that
meets the criteria of a serious adverse event should be recorded on the serious adverse event page
of the CRF.
Retinal abnormalities should be reported as adverse events or as serious adverse events if the
severity is Grade 3 or higher. Instructions for assessing vision abnormalities during the study are
provided in Section 8.3.5.
In addition, growth disorder (including accelerated bone growth  and SCFE) and fractures in
children and adolescents (≥6 to <18 years) is an adverse event of special interest for erdafitinib.
Growth disorder-related and fracture-related AEs of Grade 3 or higher severity in children and
adolescents, regardless of seriousness, will be reported to the sponsor within 24 hours.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
118
Status: Approved, Date: 22 February 2023
10.4.4. 
Procedures
All Adverse Events
All adverse events, regardless of seriousness, severity, or presumed relationship to study drug,
must be recorded using medical terminology in the source document and the CRF. Whenever
possible, diagnoses should be given when signs and symptoms are due to a common etiology
(eg, cough, runny nose, sneezing, sore throat, and head congestion should be reported as "upper
respiratory infection"). Investigators must record in the CRF their opinion concerning the
relationship of the adverse event to study therapy. All measures required for adverse event
management must be recorded in the source document and reported according to sponsor
instructions.
For all studies with an outpatient phase, including open-label studies, the subject must be provided
with a "wallet (study) card" and instructed to carry this card with them for the duration of the study
indicating the following:
 
Study number
 
Statement, in the local language(s), that the subject is participating in a clinical study
 
Investigator's name and 24-hour contact telephone number
 
Local sponsor's name and 24-hour contact telephone number (for medical personnel only)
 
Site number
 
Subject number
 
Any other information that is required to do an emergency breaking of the blind
Serious Adverse Events
All serious adverse events that have not resolved by the end of the study, or that have not resolved
upon discontinuation of the subject's participation in the study, must be followed until any of the
following occurs:
 
The event resolves
 
The event stabilizes
 
The event returns to baseline, if a baseline value/status is available
 
The event can be attributed to agents other than the study drug or to factors unrelated to study
conduct
 
It becomes unlikely that any additional information can be obtained (subject or health care
practitioner refusal to provide additional information, lost to follow-up after demonstration of
due diligence with follow-up efforts)
Suspected transmission of an infectious agent by a medicinal product will be reported as a serious
adverse event. Any event requiring hospitalization (or prolongation of hospitalization) that occurs

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
119
Status: Approved, Date: 22 February 2023
during the course of a subject's participation in a study must be reported as a serious adverse event,
except hospitalizations for the following:
 
Hospitalizations not intended to treat an acute illness or adverse event (eg, social reasons such
as pending placement in long-term care facility)
 
Surgery or procedure planned before entry into the study (must be documented in the CRF).
Note: Hospitalizations that were planned before the signing of the ICF, and where the
underlying condition for which the hospitalization was planned has not worsened, will not be
considered serious adverse events. Any adverse event that results in a prolongation of the
originally planned hospitalization is to be reported as a new serious adverse event.
 
A standard procedure for protocol therapy administration will not be reported as a serious
adverse event. (Hospitalization or prolonged hospitalization for a complication of therapy
administration will be reported as a serious adverse event).
 
Administration of blood or platelet transfusion. (Hospitalization or prolonged hospitalization
for a complication of such transfusion remains a reportable serious adverse event.)
 
Procedure for protocol/disease-related investigations (eg, surgery, scans, endoscopy,
sampling for laboratory tests, bone marrow sampling) (Hospitalization or prolonged
hospitalization for a complication of such procedures remains a reportable serious adverse
event).
 
Prolonged hospitalization for technical, practical, or social reasons, in absence of an adverse
event.
Expected progression of disease should not be considered or reported as an AE (or SAE). However,
if determined by the investigator to be more likely related to the study treatment than being
expected from the underlying disease, the treatment-invoked progression (ie the treatment-invoked
signs/symptoms of such progression) should be reported per the usual reporting requirements
(refer to Adverse Event Definitions and Classifications in Section 10.4, Adverse Events:
Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting).
Death that is attributed by the investigator explicitly to progression of disease should not be
considered nor reported as an AE (or SAE). However, if determined by the investigator to be more
likely related to the study treatment than being expected from the underlying disease, the
treatment-invoked death due to progression should be reported per the usual reporting
requirements (refer to Adverse Event Definitions and Classifications in Section 10.4: Adverse
Events: Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting).
Progression of disease and death due to disease progression should be documented on the
appropriate eCRF forms (eg, the Disease Progression form and the Death form).
Signs or symptoms of disease progression that are of clinical significance, such as spinal cord
compression, vena cava superior syndrome, major vessel rupture, efflux obstruction or organ
failure, should be documented on the appropriate eCRF forms (eg, the Clinical Progression form).

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
120
Status: Approved, Date: 22 February 2023
10.4.5. 
Contacting Sponsor Regarding Safety
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding safety issues or questions regarding the study are listed in the Contact Information
page(s), which will be provided as a separate document.
10.4.6. 
Product Quality Complaint Handling
A product quality complaint (PQC) is defined as any suspicion of a product defect related to
manufacturing, labeling, or packaging, ie, any dissatisfaction relative to the identity, quality,
durability, or reliability of a product, including its labeling or package integrity. A PQC may have
an impact on the safety and efficacy of the product. Timely, accurate, and complete reporting and
analysis of PQC information from studies are crucial for the protection of subjects, investigators,
and the sponsor, and are mandated by regulatory agencies worldwide. The sponsor has established
procedures in conformity with regulatory requirements worldwide to ensure appropriate reporting
of PQC information; all studies conducted by the sponsor or its affiliates will be conducted in
accordance with those procedures.
Procedures
All initial PQCs must be reported to the sponsor by the study-site personnel within 24 hours after
being made aware of the event.
If the defect is combined with a serious adverse event, the study-site personnel must report the
PQC to the sponsor according to the serious adverse event reporting timelines (refer to
Section 8.4.1, Time Period and Frequency for Collecting Adverse Event and Serious Adverse
Event Information). A sample of the suspected product should be maintained for further
investigation if requested by the sponsor.
Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding product quality issues are listed in the Contact Information page(s), which will be
provided as a separate document.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
121
Status: Approved, Date: 22 February 2023
10.5. Appendix 5: ECOG Performance Status Scale
Grade 
ECOG Performance Status Grade
0 
Fully active, able to carry on all pre-disease performance without restriction
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work
of a light or sedentary nature, eg, light house work, office work
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up
and about more than 50% of waking hours
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of waking
hours
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5 
Dead
Reference: Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative
Oncology Group. Am J Clin Oncol. 1982;596):649-655.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
122
Status: Approved, Date: 22 February 2023
10.6. Appendix 6: ECOG/Karnofsky/Lansky Performance Scales
The Karnofsky Scale is designed for those aged 16 years and older. The Lansky Scale is designed
for those less than 16 years of age.
The Karnofsky (Karnofsky 1948) and Lansky (Lansky 1987) Performance Scales with adaptation by the National
Marrow Donor Program® and The Medical College of Wisconsin.
Karnofsky DA, Burchenal JH. The clinical evaluation of chemotherapeutic agents in cancer. In Evaluation of
chemotherapeutic agents. Edited by MacLeod CM. New York: Columbia University Press; 1949:191-205.
Source: Lansky et. al: Toward the Development of a Play Performance (PPSC), Cancer; 56: 1837-1840.
Copyright © 1985 American Cancer Society. Reproduced with permission of John Wiley & Sons, Inc.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
123
Status: Approved, Date: 22 February 2023
10.7. Appendix 7: Cockcroft-Gault (Adults) and CKiD Schwartz (Children [≥6 to
<12 years] and Adolescents [≥12 to <18 years]) Formulas for Estimated
Creatinine Clearance
Cockcroft-Gault Formula for Estimated Creatinine Clearance for Adults
eCR = (140-Age) x Mass (Kilograms) x [0.85 if female]
                      72 x Serum Creatinine (in mg/dLl)
OR
eCcr = (140-Age) x Mass (Kilograms) x Constant
                     Serum Creatinine (in µmol/L)
Where Constant = 1.23 for men and 1.04 for women
Reference: http://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation/
CKiDa Schwartz Formula for Estimated Creatinine Clearance for Children (≥6 to <12 years)
and Adolescents (≥12 to <18 years)
GFR (ml/min per 1.73 m(2)) =39.1[height (m)/Scr (mg/dl)](0.516) x [1.8/cystatin C
(mg/L)](0.294)[30/BUN (mg/dl)](0.169)[1.099](male)[height (m)/1.4](0.188)
Reference: Schwartz GJ, Munoz A, Schneider MF, et al. New equations to estimate GFR in children with CKD. J Am
Soc Nephrol. 2009;20:629-637.
aCKiD=Chronic Kidney Disease in Children

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
124
Status: Approved, Date: 22 February 2023
10.8. Appendix 8: The Stages of Heart Failure –New York Heart Association
(NYHA) Classification
Class 
Patient Symptoms
Class I (Mild)
No limitation of physical activity. Ordinary
physical activity does not cause undue fatigue,
palpitation, or dyspnea (shortness of breath)
Class II (Mild)
Slight limitation of physical activity.
Comfortable at rest, but ordinary physical
activity results in fatigue, palpitation, or
dyspnea.
Class III
(Moderate)
Marked limitation of physical activity.
Comfortable at rest, but less than ordinary
activity causes fatigue, palpitation, or dyspnea.
Class IV 
(Severe) 
Unable to carry out any physical activity
without discomfort. Symptoms of cardiac
insufficiency at rest. If any physical activity is
undertaken, discomfort is increased.
Reference: Heart Failure Society of America The Stages of Heart Failure –NYHA Classification. Available at
http://www.abouthf.org/questions_stages.html. Accessed October 6, 2008.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
125
Status: Approved, Date: 22 February 2023
10.9. Appendix 9: Amsler Grid

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
126
Status: Approved, Date: 22 February 2023
10.10. Appendix 10: Drugs Classified as Strong or Moderate In Vivo Inhibitors
and Inducers of CYP3A4/2C9 Enzymes
Strong CYP3A4 Inhibitors
Boceprevir 
Conivaptan
Clarithromycin  
Indinavir
Grapefruit juice 
Itraconazole
Lopinavir 
Ketoconazole
Mibefradil 
Ritonavir
Nefazodone 
Nelfinavir
Posaconazole 
Conivaptan
Saquinavir 
Boceprevir
Telaprevir 
Clarithromycin
Telithromycin  
Erythromycin
Voriconazole 
Troleandomycin
Fluconazole
Strong Inhibitors: ≥5-fold increase in AUC or >80% decrease in CL.
Moderate to Strong CYP3A4 Inducers
Moderate CYP3A4 Inducers
Bosentan  
Efavirenz
Etravirine 
Modafinil
Nafcillin  
Lersivirine
Talviraline 
Tipranavir
Lopinavir
Strong CYP3A Inducers
Avasimibe 
Carbamazepine
Barbiturates eg, phenobarbital 
Phenytoin
Rifabutin  
Rifampin
St. John’s wort 
Mitotane
Enzalutamide 
Apalutamide
Strong Inducers: ≥80% decrease in area under the curve (AUC). Moderate Inducers: 50% to 80% decrease in AUC.
Moderate CYP2C9 Inhibitors
Fluconazole 
Amiodarone
Miconazole 
Piperine
Oxandrolone 
Atacigual
Tienilic acid 
Azapropazone
Bucolome 
Sulfaphenazole
Benzbromarone
Moderate CYP2C9 Inducers
Carbamazepine 
Rifampin
Enzalutamide 
Aprepitant
Reference: University of Washington’s Drug Interaction Database
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.h
tm#4
Both these references may not be exhaustive and up-to-date at any given time. Please consult the product information of ongoing
and new concomitant medications for the most accurate information on potential moderate to strong inhibitors or inducers of
CYP3A4 and CYP2C9.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
127
Status: Approved, Date: 22 February 2023
10.11. Appendix 11: List of Target Fibroblast Growth Factor Receptor (FGFR)
Mutations
Gene 
Variant 
Gene 
Variant 
Gene 
Variant 
Gene 
Variant
FGFR1 
K656E  
FGFR2 
C390YS  
FGFR3 
M528I 
FGFR4 
Y367C
FGFR1 
R189C  
FGFR2 
E565G  
FGFR3 
K650T
FGFR1 
S125L 
FGFR2 
E565Q  
FGFR3 
S371G
FGFR1 
P150S  
FGFR2 
S252L 
FGFR3 
K650N
FGFR2 
C382F  
FGFR3 
G380E
FGFR2 
P253L 
FGFR3 
E627D
FGFR2 
R251Q  
FGFR3 
Y373N
FGFR2 
A389T 
FGFR3 
Y373H
FGFR2 
S252P  
FGFR3 
D641N
FGFR2 
R210Q  
FGFR3 
S249Y
FGFR2 
S252T  
FGFR3 
A391V
FGFR2 
R203H  
FGFR3 
S249F
FGFR2 
S252A  
FGFR3 
S371R
FGFR2 
S351C  
FGFR3 
R248H
FGFR2 
Y340C  
FGFR3 
G370S
FGFR2 
G338R  
FGFR3 
R669Q
FGFR2 
S354C 
FGFR3 
P250R
FGFR2 
L617F  
FGFR3 
Y278C
FGFR2 
W290R  
FGFR3 
L324V
FGFR2 
L550F  
FGFR3 
S84L
FGFR2 
M535I 
FGFR3 
R750C
FGFR2 
Y308C  
FGFR3 
S433C
FGFR2 
E777* 
FGFR3 
K650Q
FGFR2 
K641R  
FGFR3 
S371C
FGFR2 
T370R  
FGFR3 
S249C
FGFR2 
W72C  
FGFR3 
G370C
FGFR2 
K526E 
FGFR3 
R248C
FGFR2 
D304N  
FGFR3 
Y373C
FGFR2 
K659M
FGFR2 
S267P
FGFR2 
E731K
FGFR2 
M537I
FGFR2 
F276C
FGFR2 
I547V
FGFR2 
E565A
FGFR2 
V395D
FGFR2 
W290C
FGFR2 
R678G
FGFR2 
E777K
FGFR2 
C382R
FGFR2 
S372C
FGFR2 
A315T
FGFR2 
D101Y
FGFR2 
Y375C
FGFR2 
E219K
FGFR2 
L770*
FGFR2 
L770V
FGFR2 
K659N
Note: Numbering may differ depending on which reference sequence was used.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
128
Status: Approved, Date: 22 February 2023
10.12. Appendix 12: Guidance on Study Conduct During a National Disaster for
Enrolled Subjects
It is recognized that a national disaster, eg, pandemic, may have an impact on the conduct of this
clinical study. In alignment with the recent health authority guidances, the sponsor is providing
guidance for study-related patient management in the event of disruption to the per-protocol
conduct of the study as outlined throughout the protocol. These measures are to be followed on a
temporary basis. Once the national situation allows, the usual study conduct methods will resume.
This guidance does not supersede any local or government requirements or the clinical judgement
of the Investigator to protect the health and well-being of patients and site staff. If at any time a
subject’s safety is considered to be at risk, study drug will be discontinued, and study follow-up
will be conducted, as outlined in the protocol. (Note: These measures do not apply to subjects who
have not initiated study treatment.)
Scheduled visits for safety monitoring and other protocol required assessments that cannot be
conducted in-person will be performed remotely/virtually (eg, telephone contact, telemedicine,
remote nursing, remote administration of study drug), where feasible, or delayed until the time at
which access is determined to be appropriate by the Investigator and sponsor. Study assessments
requiring investigator judgement, should be conducted by the investigator. At each contact,
subjects will be interviewed to collect adverse events data and any changes to concomitant
medications. Subjects will also be questioned regarding general health status to fulfill the physical
examination requirement.
Flexibility for all protocol-required assessments will be provided on a case by case basis, and with
agreement between the sponsor and Investigator. However, every effort should be made to adhere
to protocol-specified assessments, including follow-up, if it is in the best interest of the subject.
The sponsor will continue to monitor the conduct and progress of the clinical study and any
changes (eg, delay or discontinuation in recruitment) will be communicated to the sites and health
authorities.
Guidance specific to this protocol:
 Missed assessments or change to protocol assessments will be documented in the source
documentation and in the case report form. All study conduct performed outside of the
protocol should be documented in the source documentation.
 If a site visit is not feasible, the Investigator may discuss with the sponsor other
mechanisms for the subject to receive study drug (eg, direct to patient shipment, obtain
from another Investigative Site participating in the study). Any change in dispensing study
drug must be documented in the source documentation and eCRF.
 Safety assessments may be conducted at a local facility after discussion with the sponsor.
 Critical laboratory tests, imaging or other diagnostic tests may be done at an
authorized/certified (as legally required nationally) local laboratory or clinical facility. A

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
129
Status: Approved, Date: 22 February 2023
copy of the laboratory report must be reviewed by the Investigator and retained, along with
the reference ranges, for the source documentation and provided with the eCRF.
 Consenting of subjects for full study screening and for molecular eligibility screening will
be performed as applicable (including also remote consenting by telephone or video
consultation) according to local guidance for the informed consent.
Note: administration of non-live vaccines approved or authorized for emergency use (eg,
COVID-19) by local health authorities are allowed before or during this study. For guidance
on vaccination, please refer to National Comprehensive Cancer Network (NCCN). Preliminary
recommendations of the NCCN COVID-19 Vaccination Advisory Committee* Version 1.0
1/22/2021. 
NCCN 
https://www.nccn.org/covid-19/pdf/COVID-
19_Vaccination_Guidance_V1.0.pdf (2021), Garassino, M. C. et al. The European Society for
Medical Oncology call to action on COVID-19 vaccinations and patients with cancer:
Vaccinate. Monitor. Educate. Ann. Oncol. https://doi.org/10.1016/j.annonc.2021.01.068
(2021), and Desai et al COVID-19 vaccine guidance for patients with cancer participating in
oncology clinical trials Nature Reviews Vol18; 313 https://doi.org/10.1038/s41571-021-
00487-z.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
130
Status: Approved, Date: 22 February 2023
10.13. Appendix 13: Long-term Extension Phase
The purpose of the long-term extension (LTE) phase is to provide continued study drug to subjects,
while minimizing data collection burden; only data ofserious adverse events will be collected in
the company safety repository. Subjects in the Treatment Phase who are continuing to derive
benefit from study drug, as determined by their investigator, may have continued access to study
drug in the LTE Phase of this study (see Section 6.7). As an alternative to entering the LTE Phase,
subjects may exit the study and continue to receive treatment on a post-trial access program, when
permitted by local regulations.
For adult subjects, the LTE Phase begins with the approval of Amendment 6. For pediatric
subjects, the LTE Phase begins when the most recently enrolled pediatric subject still participating
in the study has 6 months of follow up or the last follow-up visit of the last pediatric subject,
whichever occurs first. Upon initiation of the LTE Phase, participation in the Follow-Up Phase
will end and study data collection will conclude in the clinical database. During this LTE Phase,
only serious adverse events will be reported to the company safety repository, which will be
conducted as specified in Section 8.4 using the appropriate serious adverse event reporting method.
No analyses other than routine periodic safety review encompassing reported serious adverse
events are planned for the LTE.
Study Treatment Administration
Erdafitinib may continue to be administered as described in Sections 6.1 and 6.7 of the protocol.
Prohibitions and Restrictions
Refer to protocol Section 6.5.
Study Procedures for the Long-term Extension
All subjects continuing in the LTE Phase will follow the Schedule of Activities provided in
Table 17. Clinical assessments will be conducted according to the standard of practice. Serious
adverse events will be reported to the company safety repository as specified in Table 17. Specific
safety assessments may be performed if required by local Health Authorities.
Discontinuation Criteria for the Long-term Extension
Subjects continue on study drug as defined in Section 6.7.
The assessments and timing are specified in the Schedule of Activities provided in Table 17.
Case Report Form Completion
No data will be collected in the eCRF during the LTE Phase. However, documentation of
assessments performed should be done in the subject file/source notes.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
132
Status: Approved, Date: 22 February 2023
10.14. Appendix 14: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents (TOC).
Amendments below are listed beginning with the most recent amendment.
Amendment 5 (10 November 2022)
Overall Rationale for the Amendment:  The end of study for each cohort is defined as approximately
12 months from enrollment of the last subject into the respective cohort or the last follow-up visit of the
last subject in the respective cohort, whichever occurs first. The end of study for each cohort is also
considered the “end of study data collection timepoint” for the respective cohort. The amendment also
modifies data collection during continued treatment with erdafitinib (ie, after the end of study data
collection timepoint for a cohort is reached).
The changes made to Clinical Protocol 42756493CAN2002 as part of Protocol Amendment 5 are listed
below, including the rationale for each change and a list of all applicable sections. Changes made in
previous protocol amendments are listed in Section 10.14 Appendix 14: Protocol Amendment History.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis,
Overall Design,
Intervention Groups
and Duration;
1.3 Schedule of
Activities: For
Adults (≥18 years of
age);
4.1 Overall Design;
4.3 Justification for
Dose, Adult Dose
Justification;
5.5.End of Study
Definition;
6.1 Study Drug
Administered;
6.7 Study Drug
After the End of
Study;
8.1.2 Treatment
Phase;
8.1.3 End-of-
Treatment Visit;
8.1.4 Follow-Up
Phase;
9.4.3.2 Final
Analysis;
10.3.1 Regulatory
and Ethical
Considerations
The end of study for each cohort is defined as
approximately 12 months from enrollment of the
last subject into the respective cohort or the last
follow-up visit of the last subject in the respective
cohort, whichever occurs first. The end of study for
each cohort is also considered the “end of study data
collection timepoint” for the respective cohort.
The end of study is defined as the end of study data
collection timepoint for the last open cohort.
Section 5.5 was divided in subsections: 5.5.1, End
of Study Definition Per Cohort, and 5.5.2 End of
Study Definition –Overall Study.
In the applicable sections, it was clarified that the
subject follow-up and data collection will end once
the end of study data collection timepoint has been
achieved for a cohort. Subjects who continue to
derive benefit from study treatment will be allowed
to receive study treatment and only serious adverse
events will be monitored and stored in the company
safety repository.
To revise the end of study
definition for each cohort and the
overall study, and to modify data
collection during continued
treatment with erdafitinib after the
study data collection timepoint.
To clarify monitoring of adverse
events for subjects continuing study
treatment.
1.3 Schedule of
Activities: For
Adults (≥18 years of
age);
Erdafitinib administration was indicated for the end
of treatment visit and Footnote ‘a’ in Section 1.3 and
Footnote ‘b’ in Section 1.4 were modified to include
the end of study data collection.
To indicate treatment
administration at the end-of-
treatment visit for subjects who

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
133
Status: Approved, Date: 22 February 2023
Section Number 
and Name
Description of Change 
Brief Rationale
1.4 Schedule of 
Activities: For 
Children and
Adolescents (≥6 to
<18 Years of Age)
continue to benefit from study
treatment.
1.1 Synopsis 
(Evaluations); 
1.3 Schedule of 
Activities: For 
Adults (≥18 years of 
age);
3 Objectives and
Endpoints;
4.1 Overall Design;
8.6 Biomarkers;
9.4.5 Biomarker
Analyses
Modified the exploratory biomarker objective and 
related text. 
Added that the evaluation of paired biopsies will be 
removed from Amendment 5. 
To reflect analysis deemed
meaningful for the study.
As the study continued, it became
apparent that some of the sample
collections were not feasible.
1.3 Schedule of 
Activities: For 
Adults (≥18 years of 
age)
For adult subjects remaining on treatment, PRO 
assessments were discontinued at Cycle 49. 
The PRO measures are reflective of
efficacy and the primary analysis is
complete for adult subjects.
1.4 Schedule of 
Activities: For 
Children and 
Adolescents (≥6 to
<18 Years of Age)
Clarified that there will be separate FACT-Br 
caregiver versions for child/adolescent and parent of
the child/adolescent.
To provide clarity to the site.
1.3 Schedule of 
Activities: For 
Adults (≥18 years of 
age 
During the Follow-up Phase, the European 
Organisation for Research and Treatment of Cancer 
Quality-of-life Questionnaire Core 30 (EORTC- 
QLQ-C30) and the European Quality of Life-5
Dimensions-5 Levels (EQ-5D-5L) are conducted
for the first 3 visits or until the start of subsequent
therapy.
Provided additional guidance for
the timing ofpatient reported
outcome (PRO) assessments.
10.12 Appendix 12:
Study Conduct After
End of Study Data
Collection for Each
Cohort
Deleted the appendix on continuation of treatment 
after clinical cutoff for each cohort.
Succeeding appendices were re-numbered.
To avoid repetitive information.
Throughout the 
protocol
Minor formatting changes were made. 
Minor errors were noted.
Amendment 4 (29 August 2022)
Overall Rationale for the Amendment: The overall rationale for this amendment is to remove central
molecular screening for all subjects, to add new safety assessments and palatability testing for pediatric
subjects, and to decrease the frequency of efficacy assessments for pediatric subjects. The end of study
definition has also been revised and minor clarifications have been made throughout the protocol.
The changes made to the clinical protocol 42756493CAN2002 as part of Protocol Amendment 4 are listed
below, including the rationale of each change and a list of all applicable sections. Changes made in previous
protocol amendments are listed in Section 10.14 Appendix 15: Protocol Amendment History.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
134
Status: Approved, Date: 22 February 2023
Section Number 
and Name
Description of Change 
Brief Rationale
Synopsis, Overall 
Design; 
1.2 Schema; 
8.1.1.1 Molecular 
Eligibility Screening 
Period; Figure 6 
Central molecular testing will no longer be used 
and only local reports will be used for molecular 
screening.  
Review of enrollment to date has
shown that the majority of enrolled
subjects were deemed molecularly
eligible based on local reports.
Therefore, central molecular testing
is being removed.
1.4 Schedule of 
Activities for 
Children and 
Adolescents (≥6 to 
<18 Years of Age); 
8.3.1 History and 
Physical 
Examinations; 
8.3.1.1, History and 
Physical 
Examinations for 
Children and 
Adolescent 
Subjects; 
8.3.2 Vital Signs; 
8.3.7 Bone-related 
Assessments 
(Children and 
Adolescents); 
8.4.7 Adverse
Events of Special 
Interest; 
10.4.3 Special
Reporting
Situations;
11 References
Additional Safety Assessments were added. 
In Sections 8.4.7 and 10.4.3, the Adverse Event of 
Special Interest for children and adolescent subjects 
was revised to include slipped capital femoral 
epiphysis (SCFE) and fractures, ie, now termed 
“Growth disorders (including accelerated bone 
growth and SCFE) and fractures”. Expedited 
reporting was revised accordingly, ie, growth 
disorder-related and fracture-related adverse events 
of Grade 3 or higher severity in children and 
adolescents, regardless of seriousness, will be
reported to the sponsor within 24 hours. 
Added new Section 8.3.1.1, History and Physical
Examinations for Children and Adolescent
Subjects. Information regarding Tanner Staging
previously in Section 8.3.1 relocated to this new
section.
Also, in Section 8.3.1, the text clarifies that a full
medical history will be conducted for adults.
Hip examinations and assessment
for risk factors of musculoskeletal
conditions were added to ensure
identification of pre-existing
conditions and potential risks, given
the potential risk for bone growth
abnormalities with erdafitinib
treatment. The name of the Adverse
Event of Special Interest was
revised to reflect recent safety
information.
Clarification added for the medical
history section for adults.
1.4 Schedule of 
Activities for 
Children and 
Adolescents (≥6 to 
<18 Years of Age); 
3. Objectives and 
Endpoints; 
8.1.2 Treatment 
Phase; 
9.4.8, Other 
Analyses (new); 
10.14, Appendix 14,
Pediatric Cohort
Medicine
Palatability Testing;
10.15, Appendix 15,
Protocol
Amendment History
The palatability assessment was added to the 
schedule of activities, and the other noted sections. 
Acceptability and palatability were added to
Section 3. 
Palatability testing was added to
assess a newly added exploratory
objective.
Acceptability and palatability added
as exploratory objectives to
evaluate subject compliance with
the study drug tablet in the Pediatric
Cohort in order to ensure
compliance with the Pediatric
Investigational Plan commitment.
1.4 Schedule of 
Activities for 
Children and 
Adolescents (≥6 to 
<18 Years of Age);
For pediatric subjects, radiological assessments 
were reduced to every 12 weeks. In Section 8.2, it 
was clarified that the first sentence pertains to 
adults. 
Frequency of efficacy assessments
was decreased for pediatric subjects
to reduce the burden of
assessments.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
135
Status: Approved, Date: 22 February 2023
Section Number
and Name
Description of Change 
Brief Rationale
8.2 Efficacy
Assessments;
8.5
Pharmacokinetics
In the Schedule of Activities for Children and 
Adolescents, some pharmacokinetic (PK) and 
biomarker information was aligned with the body 
of the protocol. 
Description of the PK and
Biomarker assessments in the
Schedules of Activities was
adjusted to align with the text in the
body of the protocol.
Table 1: Frequency
of FGFR Mutations
and Fusions in
Advanced Cancer
Updated mutation data was provided. 
Updated information based on last
database access.
3. Objectives and
Endpoints
Changes were made to the first Exploratory
Endpoint of the Exploratory Cohort.
Details have been added to the
protocol to specify the endpoints in
the Exploratory Cohort.
5.1 Inclusion
Criterion Number 6
Text was added to specify that the criterion does
not apply to treatment naïve pediatric subjects with
no standard of care therapies.
The change was made for
clarification.
5.1 Inclusion
Criterion Number 8
The cutoffs for the Lansky Score and the
Karnofsky Score were adjusted.
Lansky/Karnofsky ≥70 is consistent
with Eastern Cooperative Oncology
Group (ECOG) 0-1 (Appendix
10.6)
5.5 End of Study
Definition
The end of study was defined as 1 year from
enrollment of the last subject into the study or the
last follow-up visit of the last subject, whichever
occurs first
The end of study definition was
revised to align with compound
development plans.
6.7 Study Drug
After the End of the
Study;
10.3.1 Regulatory
and Ethical
Considerations
Additional information regarding the continuation
of treatment after the study was provided.
Clarified the continuation of
treatment after the study.
1.4 Schedule of
Activities for
Children and
Adolescents (≥6 to
<18 Years of Age)
During the Follow-up Phase, the Pediatric
Functional Assessment of Cancer Therapy - Brain
(Peds FACT-Br) and European Quality of Life - 5
Dimensions-5 Levels (EQ-5D-5L) are conducted
for the first 3 visits or until the start of subsequent
therapy.
Provided additional guidance for
the timing of patient reported
outcome (PRO) assessments.
8.4.1 Time Period
and Frequency for
Collecting Adverse
Event and Serious
Adverse Event
Information
“Immediately” was added to the instruction
regarding reporting of serious adverse events, ie,
reported immediately but no later than 24 hours of
their knowledge of the event.
Updated with new protocol
template wording.
6.6.1.5 Guidelines
for the Management
of Eye Toxicity
Associated with
Vision Changes
Text was adjusted to specify the reporting process
for a new retinal abnormality.
Text was corrected as described in
the Protocol Clarification Letter,
issued 10 Sept 2021.
Table 15: Guidelines
for Management of
Eye Toxicity
Visual acuity values were added to the definition
of Grade 2, Grade 3, and Grade 4 eye toxicity.
For clarity, added visual acuity
values to the definition of grades
for eye toxicity.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
136
Status: Approved, Date: 22 February 2023
Section Number 
and Name
Description of Change 
Brief Rationale
Synopsis, Number 
of Subjects; 
9.2 Sample Size 
Determination; 
9.4.3.1 Primary 
Analysis 
The timing of the primary analysis was clarified. 
“Approximately” was added to the planned
number of subjects in the Broad Panel Cohort and 
the Exploratory Cohort, ie, approximately 240 
subjects and approximately 40 subjects, 
respectively. In Section 9.2, additional information 
was provided regarding the response-evaluable 
subjects and the enrollment of adolescent subjects 
in the Broad Panel Cohort. 
Clarification was added regarding
the timing of the primary analysis.
Clarification was added regarding
the number of subjects enrolled in
the study (and the response-
evaluable subjects in the Broad
Panel Cohort), as well as adolescent
subjects enrolled in the Broad Panel
Cohort.
9.5 Interim Analyses By the discussion of interim Bayesian population 
PK and noncompartmental analysis of plasma 
concentration-time data of erdafitinib and markers 
of pharmacological activities after the enrollment
of 5 children or adolescent subjects, added that
further interim analyses may be conducted after
the enrollment of additional subjects.
Provided clarification regarding the
interim analysis for the Pediatric
Cohort.
10.3.4 Data 
Protection
Aligned section with template text. 
Aligned with protocol template
5.2 Exclusion 
Criteria 
The criterion number for modified Exclusion 
Criterion 3 was moved to top of the criterion.
Corrected number of criterion text.
2.2.1 Erdafitinib 
The National Cancer Institute and Children’s 
Oncology Group Pediatric Molecular Analysis for
Therapy Choice (NCI-COG Pediatric MATCH),
the erdafitinib substudy, text was updated based on
recent information.
Updated study information.
Throughout the 
protocol 
Minor updates or grammatical, formatting, 
abbreviation, or spelling changes were made. 
Minor errors were noted and minor
clarifications were needed.
Amendment 3 (12 August 2021)
Overall Rationale for the Amendment: To add a Pediatric Cohort (≥6 to <18 years of age) for
children and adolescents with locally advanced or metastatic solid tumors harboring FGFR
alterations who have either progressed following prior therapies and who have no acceptable
standard therapies, or who have a newly-diagnosed solid tumor and who have no acceptable
standard therapies. This cohort also includes children and adolescent subjects who are enrolled in
the Broad Panel Cohort.
The dosing and titration schedule was amended to include dosing instructions for subjects ≥6 to
<12 years of age (added due to addition of this age group within the protocol) and to amend the
titration schedule for subjects ≥12 to <15 years of age in order to align with PK-PD simulation and
modelling. Based on the PK and PD model, a 2-week dosing interval was selected as it allows PK
and PD to reach steady-state and leads to satisfactory efficacy and safety proportions.
Section number
and Name
Description of Change 
Brief Rationale
Synopsis (Objectives, Overall
Design, Number of Subjects,
Addition of a Pediatric Cohort (≥6 to <18 
years of age) to include 20 children and 
To extend the lower age
limit of subjects included

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
137
Status: Approved, Date: 22 February 2023
Section number 
and Name
Description of Change 
Brief Rationale
Intervention Groups and Duration, 
Statistical Methods), 1.2 Schema, 1.4 
Schedule of Activities, 2.2.3 
Fibroblast Growth Factor Receptor 
Alterations in Solid Tumors, 
3 Objectives and Endpoints, 4.1 
Overall Design, 4.2 Scientific 
Rationale for Study Design, 
4.3 Justification for Dose, 
5.1 Inclusion criteria, 6.1 Study Drug 
Administered, 6.6 Dose 
Modifications, 8.5 Pharmacokinetics,
9.2 Sample Size Determination, 9.3.4 
Pediatric Cohort, 9.4.3.1 Primary 
Analysis, 9.4.4 Pharmacokinetic and 
Pharmacodynamic Analyses. 
adolescent subjects who have progressed 
following prior therapies and who have no 
acceptable standard therapies, and 
approximately 6 additional children and 
adolescent subjects who have a newly- 
diagnosed solid tumor and who have no 
acceptable standard therapies. Clarification 
that adolescent subjects enrolled in the
Broad Panel Cohort will be analyzed as
part the Broad Panel Cohort and the
Pediatric Cohort.
Other sections were revised to add specific
aspects of the Pediatric Cohort. In Section
2.2.3, Justification for inclusion of
Pediatric Cohort was added. In the
synopsis and Section 3, the objective for
the Pediatric Cohort was added. To the
listed dosing sections, added dosing
information for subjects ≥6 to <12 years of
age. To the synopsis and Sections 4.1 and
9.3.4, added endpoints for the Pediatric
Cohort, and clarified that subjects in the
Pediatric Cohort will be analyzed as part of
the Broad Panel Cohort and Pediatric
Cohort. Statistical analyses for Pediatric
Cohort added to Section 9.
Pharmacokinetic sampling instructions
added to Section 8.5 for subjects ≥6 to
<12 years of age.
in the study from ≥12 to ≥6
years, and to include a
broader range of FGFR
alterations to ensure that an
adequate selection of
pediatric subjects will be
treated with erdafitinib.
Synopsis Intervention Groups and 
Duration, 1.2 Schema, 1.4 Schedule 
of Activities, 4.1 Overall Design, 4.3 
Justification for Dose, 6.1 Study 
Drug Administered, 6.6, Dose 
Modifications, 8.5 Pharmacokinetics. 
Change to dose titration schedule for 
≥12 to <15 years of age, with first possible 
up- titration at Cycle 1 Day 14 (previously 
Cycle 1 Day 7) and second possible up- 
titration at Cycle 2 Day 7 (previously 
Cycle 1 Day 14). 
Pharmacokinetic sampling frequency 
amended from Cycle 1 Day 7 and Cycle 1 
Day 14, to Cycle 1 Day 14 and Cycle 2 
Day 14.
Based on PK-PD
modeling, a 2-week dosing
interval was selected for
subjects ≥12 to <15 years
of age. This interval allows
PK and PD to reach
steady-state and leads to
satisfactory efficacy and
safety proportions.
1.4 Schedule of Activities: For 
Children and Adolescents (≥6 to <18 
Years of Age), 4.2.3 Patient-reported 
Outcomes Research, 8.7 Patient- 
reported Outcomes
Addition of Pediatric Functional 
Assessment Of Cancer Therapy –Brain 
(Peds FACT-Br) for use in subjects <18 
years of age. 
To be used for subjects
<18 years of age as
EORTC-QLQ-C30 is not
validated for pediatric use.
Synopsis Objectives and Statistical 
Methods, 3 Objectives And 
Endpoints, 9.4.2 Secondary Efficacy 
Endpoints, 9.4.3.1 Primary Analysis.
Addition of clinical benefit rate (CBR) as a 
measure of efficacy. 
Clinical benefit rate is a
clinically-relevant measure
of efficacy in this study.
Synopsis Statistical Methods, 4.1 
Overall Design, 9.3.3 
Cholangiocarcinoma Expansion 
Cohort
Clarification that Cholangiocarcinoma 
Expansion Cohort will be evaluated
separately from the Broad Panel Cohort.
Amended for clarity.
Synopsis Overall Design, 6.7 Study 
Drug After the End of the Study, 
Language added relating to post-trial 
access to study treatment. 
To clarify that the sponsor
will ensure subjects who

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
138
Status: Approved, Date: 22 February 2023
Section number 
and Name
Description of Change 
Brief Rationale
10.3.1. Regulatory and Ethical 
Considerations, 10.12. Appendix 12: 
Continuation of Treatment After 
Clinical Cutoff for the Final 
Analysis.
are benefiting from study
treatment will have
continued access to study
drug.
1.3 Schedule of Activities: For 
Adults (≥18 Years of Age), 1.4 
Schedule of Activities: For Children 
and Adolescents (≥6 to <18 Years of 
Age). 
Addition that history of seizure activity 
should be included within the neurological 
examination and detailing relevant subjects 
for this assessment.
Addition that for Radiological assessment
and/or skin photography, as applicable,
after Week 48, the next radiological
assessment will be performed at Week 60.
Clarification regarding
neurological exam and
timing of assessments.
5.2 Exclusion criteria, 
10.11 Appendix 11 List of Target 
Fibroblast Growth Factor Receptor 
(FGFR) Mutations
List of eligible FGFR mutations to be
included was revised. Update to exclusion
criteria for NSCLC and colorectal subjects.
Change to eligibility
criteria of the study based
on predicted likelihood for
pathogenicity.
2.3 Benefit-Risk Assessment 
Addition of text relating to subjects <6
years of age
These subjects will not be
included in the study as an
age-appropriate
formulation is not yet
available.
4.1 Overall Design, 8.1.1.1 
Molecular Eligibility Screening 
Period, 9.2 Sample Size 
Determination, 9.5 Interim Analyses
Clarification regarding sample size cap for 
each tumor histology. 
Additional detail included
regarding tumor histology
cap.
2.2.1 Erdafitinib 
Summary of subprotocol of the NCI-COG- 
sponsored Pediatric MATCH Trial 
APEC1621B added. 
To add details of this
pediatric study of
erdafitinib.
6.1 Study Drug Administered 
Guidance for subjects with CYP2C9 *3/*3 
genotype added. 
To provide guidance for
subjects with CYP2C9
*3/*3 genotype
6.5.3 Precautions for Concomitant 
Medications 
Updated precautions to specify that 
moderate CYP2C9 (strength previously 
not stated) inhibitors should be used with 
caution. Guidance for use with CYP3A4
substrates and OCT2 substrates added.
Aligned with updates to
Investigator’s Brochure
Edition 10.
6.1 Study Drug Administered 
Presentation of information for adolescents 
and adults updated to group information
for each age category and flow-chart added
to illustrate titration schedule.
Amended for clarity.
8.4.7 Adverse Events of Special 
Interest, 10.4.3 Special Reporting 
Situations 
Corneal or retinal abnormalities were 
removed as adverse events of special 
interest. 
Corneal or retinal
abnormalities are no longer
considered adverse events
of special interest but
should continue to be
reported as adverse events
or as serious adverse
events if the severity is
Grade 3 or higher.
6.6.1.1 Guidelines for the 
Management of Elevated Phosphate 
Levels 
Pediatric dosing guidance added for 
sevelamer. 
Dosing guidance for
pediatric subjects added in
line with addition of
Pediatric Cohort.
8.7 Tumor Markers 
New section added. 
To ensure capture of data

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
139
Status: Approved, Date: 22 February 2023
Section number 
and Name
Description of Change 
Brief Rationale
relating to tumor markers
were collected as part of
routine care.
6.5.1 Permitted Medications 
Text added relating to coronavirus disease 
2019 (COVID-19) vaccination. 
Guidance added relating to
COVID-19 vaccination.
6.5.3 Precautions for Concomitant 
Medications 
Paragraph added with instruction regarding 
OCT2 substrates. Also, added a statement 
that until further data become available, 
concomitant use of erdafitinib with
CYP3A4 substrates with narrow
therapeutic indices should be avoided.
Text added in line with
updated Investigator’s
Brochure Edition 10.
9.4.3.1 Primary Analysis 
Clarification that the primary analysis will 
be conducted 6 months after enrollment of 
200 response-evaluable subjects have been
treated.
Previously described as
240 subjects.
6.6.1.2 Guidelines for the 
Management of Dry Mouth and 
Mucositis, 6.6.1.3 Guidelines for the 
Management of Dry Skin and Skin 
Toxicity, 6.6.1.4 Guidelines for the 
Management of Nail Toxicity
(Onycholysis, Onychodystrophy, and
Paronychia), 6.6.1.5 Guidelines for
the Management of Eye Toxicity
Associated With Vision Changes
Minor edits were added throughout these 
tables. 
Harmonization of
presentation of toxicity
management guidance
across the development
program.
4.2.5 Participant Input Into Design  
Explanation of how the results of the study 
may be made available to participants. 
To comply with an update
to the company template.
8.4.1 Time Period and Frequency for 
Collecting Adverse Event and 
Serious Adverse Event Information,
10.2. Appendix 2: Clinical
Laboratory Tests
Definition of potential Hy’s Law case 
added. 
Per update to company
protocol template.
10.3.1 Regulatory and Ethical 
Considerations 
Addition of text relating to protocol 
clarification communications 
Per update to company
protocol template.
10.4.2 Severity Criteria 
Alignment of text with most recent 
company protocol template. 
Per update to company
protocol template.
10.4.4 Procedures 
Clarification of text regarding disease 
progression. 
Per update to company
protocol template.
10.13 Appendix 13: Guidance on 
Study Conduct During a National 
Disaster for Enrolled Subjects
Guidance relating to administration of non- 
live vaccines added. 
Per update to company
protocol template.
Title page 
Addition of IND number. 
Per company template.
5.2 Exclusion criteria 
Timeframe for exclusion based on prior 
therapy amended to <5 half-lives of the 
agent.
Correction of
typographical error.
Throughout the protocol 
Minor grammatical, formatting, or spelling 
changes were made.
“He” or “she” were replaced by “the 
subject”. 
Minor errors were noted.
To adhere to the current
company standards for
gender inclusivity.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
140
Status: Approved, Date: 22 February 2023
Amendment 2 (19 Aug 2020)
Overall Rationale for the Amendment: Revised inclusion and exclusion criteria based on new insights related
to eligibility; expanded enrollment for subjects with cholangiocarcinoma histology.
Section Number 
and Name
Description of Change 
Brief Rationale
Synopsis; 1.3. Schedule of 
Activities for Adults; 1.4. Schedule 
of Activities for Adolescents; 5.1. 
Inclusion Criteria (Number 2.2); 
8.1.1.1. Molecular Eligibility 
Screening Period 
Updated the list of local molecular testing 
methods to include direct digital counting 
methods and the Qiagen therascreen® 
FGFR RT-PCR test 
Specified FGFR gene fusions must have 
an intact FGFR kinase domain as follows
(formerly included exon 16, 17 or 18):
FGFR fusion with a 3-prime partner
(FGFR gene is listed first, eg FGFR-
GENE or FGFR3-TACC3); FGFR
portion of fusion must involve exon
≥17
FGFR fusion with a 5-prime partner
(Partner gene is listed first and FGFR
gene is second, eg GENE-FGFR or
KLK2-FGFR2); FGFR portion of
fusion must involve exon ≤11
Named FGFR fusion partner gene
(self-fusions or rearrangements, eg
FGFR-FGFR, are not eligible)
The gene identifiers table was updated for
correctness and clarity.
Other FGFR mutations for enrollment in
the Exploratory Cohort were further
defined as protein-coding single
nucleotide variant (SNV) and insertions
or deletions (indels):
To provide updates and
clarify molecular eligibility
methods and criteria; update
FGFR gene identifiers and
canonical transcript
identifiers
1.3. Schedule of Activities for 
Adults; 1.4. Schedule of Activities 
for Adolescents; 8.1.1.1. Molecular 
Eligibility Screening Period; 
Figure 3 
The following was added: 
Biopsy of the brain, lung/mediastinum, 
pancreas, or for endoscopic procedures 
extending beyond the esophagus, stomach, 
or bowel is not permitted; please contact 
Sponsor prior to conducting biopsy. 
To restrict biopsy of the
brain, lung/mediastinum,
pancreas, or for endoscopic
procedures extending
beyond the esophagus,
stomach, or bowel
5.2. Exclusion Criteria 
(Number 2.1) 
The following was added: 
Observation of a gatekeeper/resistance 
alteration in the local or central report. If 
the local test does not screen for all four
FGFRs, eg, FGFR4, the local report
remains evaluable for molecular
screening.
To define “known” FGFR
gatekeeper/resistance
alterations
5.2. Exclusion Criteria 
(Number 3.2) 
Updated as follows: 
For NSCLC subjects only –pathogenic 
somatic mutations in EGFR* or BRAF 
To clarify NSCLC molecular
screening methods and
update exclusionary
mutations and gene fusions

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
141
Status: Approved, Date: 22 February 2023
Section Number 
and Name
Description of Change 
Brief Rationale
V600E, or any gene fusions in the
following genes: ALK, ROS1, or NTRK.
* Assessment of these genes may be
performed per institutional standard and
do not have to be assessed via NGS
5.1 Inclusion Criteria (Number 2.2) 
Deleted note that central screening for 
breast cancer is limited to women with 
hormone-sensitive (ie, estrogen positive 
[ER]/progesterone positive [PR]) breast 
cancer. 
Not applicable for study
eligibility; selective tumor
histologies for central
screening is fully described
in other sections of the
protocol
5.1. Inclusion Criteria (Number 4.1) 
Updated inclusion criterion to include 
advanced and unresectable settings 
To align with 5.1 Inclusion
Criteria (Number 2.1)
5.1. Inclusion Criteria (Number 9.2) 
Deleted the following: 
/1.73m2 either directly measured via
24 hour urine collection or
Minor revision
5.2. Exclusion Criteria 
(Number 1.1) 
Updated the washout for prior 
chemotherapy, targeted therapy, or 
treatment with an investigational 
anticancer agent to: within 15 days 
(previously 30 days) or ≥5 half-lives 
(whichever was longer) and up to a 
maximum of 30 days; added restriction 
for prior monoclonal antibody within 
30 days
A shorter minimum washout
period may be sufficient for
some prior therapies (ie,
shorter than 30 days).
Monoclonal antibody
therapy washout was
previously inadvertently
omitted.
5.2. Exclusion Criteria 
(Number 4.1) 
Updated to exclude all urothelial 
carcinoma (previously specified 
transitional cell carcinoma of the
urothelium).
To align with indication
statement
5.2. Exclusion Criteria 
(Number 8.1) 
Clarified that prior selective FGFR 
inhibitor treatment is not permitted 
To specify only selective
FGFR inhibitors are
exclusionary
5.2. Exclusion Criteria 
(Number 11.2) 
Revised exclusion for heart failure to 
Class III-IV (previously Class III-V)
Minor revision
5.2. Exclusion Criteria 
(Number 13.2) 
Updated to allow enrollment of subjects 
with inactive hepatitis B with a positive 
HBsAg antibody or normal PCR  
To allow subjects with
inactive hepatitis to be
eligible for study
participation
5.2. Exclusion Criteria 
(Number 17.1) 
Clarified to specify that palliative 
radiation to the target lesion within 2 
weeks before the first dose of erdafitinib 
was not permitted.
To clarify palliative
radiation was restricted for
only the target lesion
Synopsis; Figure 1; 
3.1. Cholangiocarcinoma Expansion 
Cohort; 4.1 Overall Design; Figure 
2; 4.2.1 Cohort Design; 9.2 Sample 
Size Determination; 9.3.3
Cholangiocarcinoma Expansion
Cohort
Added a Cholangiocarcinoma Expansion 
Cohort and removed text specifying 
further enrollment “up to 60 subjects per 
each tumor histology” 
To allow expanded
enrollment of subjects with
cholangiocarcinoma in a
separate cohort
2.2.3. Fibroblast Growth Factor 
Receptor Alterations in Solid 
Tumors, Table 1 
Updated to add central testing for salivary 
gland tumors, colorectal cancer, and 
thymic cancer/thymoma; specify high- 
grade gliomas (eg, glioblastoma) and 
low-grade gliomas 
To allow central molecular
testing for subjects with
salivary gland tumors,
colorectal cancer, and
thymic cancer/thymoma; to
clarify low- and high-grade

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
142
Status: Approved, Date: 22 February 2023
Section Number
and Name
Description of Change 
Brief Rationale
Predominant alteration types column is 
added to Table 1. 
gliomas; to add alteration
types information
2.2.3. Fibroblast Growth Factor
Receptor Alterations, Pediatric
Solid Tumors
Updated references 
Minor revision  
4.1. Overall Design; Figure 3 
Central molecular screening updated to
add salivary gland tumors, colorectal, and
thymic cancer/thymoma; to specify high-
grade gliomas (eg, glioblastoma), low-
grade gliomas; and squamous NSCLC; to
specify hormone-sensitive breast cancer
(estrogen positive [ER]/progesterone
positive [PR])
The following text is also added:
Central screening for any tumor type will
be allowed for pediatric subjects or if a
local report is deemed insufficient.
Added that central molecular testing
should be performed for subjects who can
be eligible for study participation within
6 months of testing.
To allow central molecular
testing for subjects with
salivary gland tumors,
colorectal cancer and thymic
cancer/thymoma, to clarify
low- and high-grade
gliomas; to specify
squamous NSCLC and
hormone-sensitive breast
cancer; to allow central
molecular testing for any
tumor type in pediatric
subjects and subjects with an
insufficient local report;
To limit central testing to
patients who can participate
6.5.1. Permitted Medications; 
6.5.2. Prohibited Medications 
Updated to allow ongoing adjunct
hormonal therapy in subjects with breast
cancer or prostate cancer who progressed
while receiving the hormonal therapy and
had been receiving the therapy for at least
6 months
To allow ongoing, long-term
adjunctive hormonal therapy
for subjects with breast
cancer or prostate cancer
6.5.3. Precautions for Concomitant 
Medications; 10.10 
Updated fluconazole as a moderate
CYP2C9 inhibitor (previously considered
a strong inhibitor); updated to state that
caution should be used with moderate
CYP3A inducers.
Added the following:
Based on in vitro data, erdafitinib is
metabolized by cytochrome CYP2C9 and
CYP3A4. The impact of moderate
CYP2C9 inducers and strong CYP3A4
inducers (such as rifampin) on erdafitinib
was not clinically studied. The
concomitant use of these agents with
erdafitinib should be avoided
To align with updated FDA
classification of inhibitors or
inducers of CYP2C9 and
CYP3A
8.2. Efficacy Assessments; 8.2.2 
Continuation of Treatment 
Updated the investigator assessment of
suspected progression to include IRC
confirmation; removed the requirement for
treatment discontinuation if the repeat
imaging meets the threshold of
progressive disease.
To allow consideration of
IRC assessment prior to
treatment discontinuation
and remove the requirement
for discontinuation if repeat
imaging meets threshold of
progressive disease
8.2.1.1. RECIST and RANO
Assessment of Disease; References
Updated RANO references (Wen 2010
and van den Bent 2011), including
assessment criteria for both low- and high-
grade gliomas
To provide assessment
reference for low- and high-
grade gliomas

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
143
Status: Approved, Date: 22 February 2023
Section Number
and Name
Description of Change 
Brief Rationale 
1.3. Schedule of Activities for 
Adults; 1.4. Schedule of Activities 
for Adolescents; 8.2. Efficacy
Assessments; 8.2.1.2. Radiographic
Assessment
Added skin lesion photography as an
efficacy assessment as applicable
To allow for photography
assessments when
radiological assessment is
not feasible
Synopsis; 1.4. Schedule of 
Activities for Adolescents; 
3. Objectives; 
8.5. Pharmacokinetics;
9.4.4. Pharmacokinetic and 
Pharmacodynamic Analyses 
Added serial PK samples for adolescents
on Cycle 3, Day 1 and Cycle 4 Day 1;
deleted samples on Cycle 2, Day 1
Moved protein binding sample to Cycle 3,
Day 1 (previously Cycle 2, Day 1)
Updated the PK endpoints to indicate both
adults and pediatric subjects; removed
population PK analysis from the
secondary endpoint
To fully characterize the PK
profile in adolescents
To align with PK sampling
To remove a secondary
endpoint linked to an
optional analysis (population
PK)
1.3. Schedule of Activities 
Changed fresh tumor biopsy assessment to
read as optional (previously ‘where
clinically feasible’); specified sampling at
the time of disease progression
(previously end of treatment)
To clarify that fresh tumor
biopsy is optional and
timepoint for sampling
Figure 2 
Added a footnote that the Exploratory
Cohort is closed for enrollment
To indicate that the
Exploratory Cohort
enrollment is completed
4.2.4. Study-Specific Ethical Design 
Considerations 
Updated total blood volume collected for
adolescents on Cycle 1 Day 1 visit
To indicate that collection
exceeds the maximum
30 mL on Cycle 1 Day 1
4.3. Justification for Dose 
Updated for flow and to strengthen 
justification for adult dosing 
Updated for flow and to
strengthen justification for
adult dosing
5.3. Lifestyle Considerations 
The following was added: 
Male and female subjects should be 
advised on sperm banking and egg 
preservation, respectively, prior to
entering the study, if appropriate.
To address a request from a
regulatory authority in the
clinical program
6.5.1. Permitted Medications 
Added that surgery or biopsy of target 
lesions is not permitted 
To prohibit surgery or
biopsy of target lesions
6.1. Study Drug Administered, Up- 
titration Guidelines; 6.6.1.1 
Guidelines for the Management of 
Elevated Phosphate Levels, Table 5 
and Table 6 
Values for grading of hyperphosphatemia 
have been revised throughout the protocol 
to include 2 decimals, for consistency with 
the case report form (CRF), and 
instructions for rounding the second 
decimal point were deleted.
To ensure consistency
between the protocol and
CRF guidelines, harmonize
rounding of phosphate
values
6.6.1.2. Guidelines for the 
Management of Dry Mouth and 
Mucositis ,Table 7, Table 8, 
6.6.1.3 Guidelines for the 
Management of Dry Skin and Skin 
Toxicity, Table 9; 
6.6.1.4. Guidelines for the 
Management of Nail Toxicity 
(Onycholysis, Onychodystrophy, 
and Paronychia), Table 11 
Updated toxicity guidelines for general 
prophylaxis; updated guidance for 
management of oral mucositis and nail 
discoloration  
To improve adherence to
and consistency in
management of adverse
events, as oral mucositis and
nail toxicity were commonly
observed adverse events in
the study so far, and for
consistency with National
Cancer Institute Common
Terminology Criteria for
Adverse Events (NCI-
CTCAE) guidelines

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
144
Status: Approved, Date: 22 February 2023
Section Number 
and Name
Description of Change 
Brief Rationale
6.6.1.4. Guidelines for the 
Management of Nail Toxicity 
(Onycholysis, Onychodystrophy, 
and Paronychia), Table 10
Deleted “Hyperphosphatemia” from the 
table title
.
To align with table content
8.1. Screening Phase 
Added that Full-study informed consent 
form (ICF) and Molecular Eligibility ICF 
may be combined or collected at the same 
time 
To allow sites to combine
Full-study ICF and
Molecular Eligibility ICF for
subjects entering with local
NGS results or consent on
the ICFs at the same time
8.2.1.2. Radiographic Assessment 
(previously Radiographic Images 
Assessment) 
Added that imaging should be performed
as scheduled irrespective of study drug
interruption (previously not delayed due to
delays in cycle starts or extension of cycle
intervals); added that the End-of-
Treatment Visit should occur after
discontinuation of treatment (previously
disease progression)
To align with study design 
8.3.2. Vital Signs 
Removed the specification for methods of 
temperature assessment
Minor revision
8.3.3. Electrocardiograms 
Clarified that ECG assessments for on- 
study visits are required, and are to be 
conducted postdose if possible 
To clarify ECG assessments
for on-study visits are
required
8.3.5 Ophthalmologic Examination  
Added that Optical Coherence 
Tomography (OCT) and fluorescein 
angiography images should be stored in
the subject’s records if performed, and to
contact the sponsor when only a PDF
imaging is available
To clarify ophthalmologic
images storage
1.3. Schedule of Activities for 
Adults; 1.4. Schedule of Activities 
for Adolescents; 8.4.1. Time Period 
and Frequency for Collecting
Adverse Event and Serious Adverse
Event Information
Removed the following: 
“or before the start of subsequent cancer 
therapy, whichever is longer,” 
Standardization across
erdafitinib (monotherapy)
protocols
8.4.6. Disease-relate Events Not 
Qualifying as Adverse Event; 
Appendix 4 Adverse Events: 
Definitions and Procedures for
Recording, Evaluating, Follow-up,
and Reporting, Procedures
Updated protocol template language 
replaced by existing protocol text 
To align with updated
company protocol template
language
8.4.7 Adverse Events of Special 
Interest; 10.4 Appendix 4 Adverse 
Events: Definitions and Procedures 
for Recording, Evaluating, Follow- 
up, and Reporting, Special 
Reporting Situations 
Deleted special reporting of Grade 1 and 
Grade 2 corneal and retinal abnormalities 
Unlike Grade 1 and Grade 2
corneal and retinal
abnormalities, Grade 3 and
higher central serous
retinopathy events are
potentially medically
significant events and should
be reported as serious
adverse events
Synopsis; 4.2.3. Patient-reported 
Outcomes Research; 8.7. Patient- 
reported Outcomes; 9.4.6. Medical 
Resource Utilization and Patient-
reported Outcomes Analyses
Text specifying hypothesis testing, 
treatment group comparisons, and time to 
events analyses were deleted
To delete nonapplicable text
for PRO analyses

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
145
Status: Approved, Date: 22 February 2023
Section Number 
and Name
Description of Change 
Brief Rationale
9.4.3.1. Primary Analysis; 
9.4.3.2. Final Analysis; 9.5 Interim  
Analysis, Figure 4 
Efficacy analysis plan updated for the 
primary analysis to be conducted 6 months 
after enrollment of240 subjects; text 
reorganized for clarity; final analysis
information added; deleted final analysis
graphic from Figure 4
To clarify timing of primary
analysis and plan for final
analysis
1.3. Schedule of Activities for 
Adults; 1.4. Schedule of Activities 
for Adolescents 
Added for parathyroid hormone 
assessments may be performed within 3
days prior to D1 of each cycle
To clarify visit window
1.3. Schedule of Activities for 
Adults; 1.4. Schedule of Activities 
for Adolescents
Edited the table header for Cycle 1 Day 1 
to: C1:-3 days to D1 
To remove reference to
Day 0
1.3. Schedule of Activities for 
Adults; 1.4. Schedule of Activities 
for Adolescents (footnotes) 
Clarified that the 30-day screening visit 
window starts with the first planned study 
procedure other than the tissue biopsy
and informed consent
To clarify screening visit
window
1.4. Schedule of Activities for 
Adolescents 
Edited the table header for Day 7 to 
specify visit assessment only on Cycles 1 
and 2 (+ 2 days)
To clarify Day 7 assessment
cycles for adolescents
1.4. Schedule of Activities for 
Adolescents 
Specified in header that Day 7 
assessments apply to Cycle 1 and Cycle 2 
only  
To clarify Day 7
assessments for adolescent
subjects
10.9 Appendix 9 Amsler Grid 
Updated the Amsler grid 
To use updated Amsler grid
1.3. Schedule of Activities for 
Adults; 1.4. Schedule of Activities 
for Adolescents; 8.1.1.1. Molecular 
Eligibility Screening Period; 10.12 
Appendix 12 Guidance on Study 
Conduct During a National Disaster
Added National Disaster appendix 
(appendix is cross-referenced in a footnote 
to the Schedules of Activities) 
Added guidance for remote consent as
applicable per local guidance
To provide instructions to be
followed during a national
disaster
1.3. Schedule of Activities for 
Adults; 1.4. Schedule of Activities 
for Adolescents (footnotes) 
Added footnote to allow patient reported 
outcome (PRO) measures to be conducted 
using Interview Mode, if necessary.
To allow PRO assessment
using Interview Mode
Title page and footer 
Updated confidentiality information added To update information
Throughout the protocol 
Removed the numbering from the 
References and using only parenthetical 
referencing
To align with updated
company protocol template
Throughout the protocol 
The term “patient” was changed to 
“subject” as appropriate
Minor errors were noted
Throughout the protocol 
Minor grammatical, formatting, or 
spelling changes were made.
Minor errors were noted

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
146
Status: Approved, Date: 22 February 2023
Amendment 1 (15 August 2019)
The overall reason for this amendment: To add a mutation to the list of excluded mutations and gene fusions
for subjects with non-small cell lung cancer (NSCLC) and add the actual List of Target Fibroblast Growth Factor
Receptor (FGFR) Mutations to the protocol as requested by the United States Food and Drug Administration
(FDA).
Applicable Section(s) 
Description of Change(s)
Rationale: To add BRAF V600E to the list of excluded pathogenic somatic mutations or gene fusions for subjects
with NSCLC as requested by the FDA.
5.2. Exclusion Criteria (Number 3) 
The above-mentioned mutation was added to Exclusion Criterion 3 (now
numbered 3.1).
Rationale: To add the actual List of Target Fibroblast FGFR Mutations as requested by the FDA.
1.2. Schema 
(Figure 1 Footnote “d”); 
4.1. Overall Design 
(Figure 2 Footnote “a”); 
4.2.1. Cohort Design;
5.1. Inclusion Criteria (Number 2);
9.3.1. Broad Panel Cohort;
10.11. Appendix 11: List of Target
FGFR Mutations
The location of the List of Target FGFR Mutations (required for inclusion
in the Broad Panel Cohort) has been changed from the Laboratory Manual
to Appendix 11 in Section 10.11; this change has been noted in the sections
listed to the left (ie, under “Applicable Sections”).
Figure 1 (footnote e); 
Figure 2 (footnote b); 
4.2.1. Cohort Design;
5.1. Inclusion Criteria (Number 2)
Clarification has been added that FGFR gene fusions must have an intact
FGFR kinase domain.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
147
Status: Approved, Date: 22 February 2023
Rationale: Updated the instruction regarding strong CYP3A4 and CYP2C9 inhibitors for consistency with the
Investigators Brochure.
6.5.3. Precautions for Concomitant 
Medications; 
10.10. Appendix 10: Drugs 
Classified as . . . 
In Section 6.5.3 (first bullet), the text regarding the change in erdafitinib
exposure with strong CYP3A4/2C9 inhibitors was replaced with the
following text: “For this reason, strong CYP3A4 and CYP2C9 inhibitors
should be used with caution. Consider alternative therapies that are not
strong inhibitors of CYP2C9 or CYP3A4 during treatment with
erdafitinib. If co-administration of a strong inhibitor of CYP2C9 or
CYP3A4 is unavailable, monitor the subject closely for adverse reactions
and consider dose modifications accordingly. If the strong inhibitor is
discontinued, the erdafitinib dose may be increased in the absence of drug-
related toxicity.”
The appendix heading was updated and strong in vivo inhibitors of
CYP3A4/2C9 were added to Appendix 10.
Rationale: The Amsler Grid Tests was added at Cycle 3 Day 1 (C3D1) and is now consistent with the Adolescent
Schedule of Activities.
1.3. Schedule of Activities for Adults 
. . .
The Amsler Grid Test was added at C3D1.
Rationale: Simplified the exclusion criterion regarding hepatitis.
5.2. Exclusion Criteria (Number 13) 
Revised Exclusion Criterion 13 (now 13.1) to state: “Evidence of active
hepatitis B or C infection (for example, subjects with history of hepatitis
C infection but normal hepatitis C virus polymerase chain reaction test and
subjects with hepatitis B with positive HBsAg antibody are allowed).” The
previous text was “Known active Hepatitis B or C infection (unless
polymerase chain reaction [(PCR] negative [according to local laboratory
range] on all available tests for the past 6 months).”
Rationale: Added the Chronic Kidney Disease in Children (CKiD) Schwartz Formula for estimation of creatinine
clearance in adolescents, as it is deemed more accurate than adult formulas.
5.1. Inclusion Criteria (Number 9c); 
10.7. Appendix 7 
Added the CKiD Schwartz Formula to Inclusion Criterion 9 for estimation
of creatinine clearance in adolescents. The CKiD Schwartz Formula with
reference was added to Appendix 7. The Appendix 7 title was revised
accordingly and new subheaders were added to distinguish between the
adult and adolescent formulas.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
148
Status: Approved, Date: 22 February 2023
Rationale: Assessment of additional hormones that play a role in childhood growth were added to the list of clinical
laboratory tests for adolescent subjects.
1.4. Schedule of Activities: 
Adolescents . . .; 
4.2.4. Study-specific Ethical Design 
Considerations; 
8. Study Assessments and Procedures; 
10.2. Appendix 10.2 
The following clinical laboratory tests were added to the Schedule of
Activities for Adolescents: thyroid stimulation hormone (TSH), total
triiodothyronine (T3), and free thyroxine (T4). These tests were added at
screening and Day 1 of every odd-numbered cycle, and at end of
treatment (these tests were mentioned in Appendix 2 in Section 10.2 of
the original protocol). Insulin-like growth factor 1 (IGF-1) was added at
screening and at the time of the DEXA scan. The abbreviations for these
tests were added to the abbreviation list at the end of this table. Also, IGF-
1 was added to Appendix 2 in Section 10.2.
The blood volume for adolescents was updated in Sections 4.2.4 and 8,
ie, the blood volume was changed from approximately 280 mL to 275 mL
over 6 cycles.
Rationale: The sample size calculation has been adjusted (ie, the power).
9.2. Sample Size Determination  
The sample size calculation has been adjusted as follows: The sample size
of 200 response-evaluable subjects for the Broad Panel Cohort is selected
based on extensive simulations with various Bayesian hierarchical model
designs to achieve approximately 80% (previously 85%) power to select
80% tumor histologies (eg, ≥12 of 15 [previously 8 of 10] tumor
histologies) for the final analysis if the true ORR is 35% for each tumor
histology.
Rationale: Clarified the timing of some of the Patient Report Outcome (PRO) assessments, ie, the Patient Global
Impression of Change (PGIC), the EORTC-QLQ-C30, and the EQ-5D-5L. In addition, the order in which the PRO
assessments should be conducted was clarified.
1.3. Schedule of Activities: For 
Adults . . .; 
1.4. Schedule of Activities: For 
Adolescents . . .; 
8.7. Patient Reported Outcomes 
Timepoints for assessment of PGIC have been limited to Cycle 2 Day 1,
and the EoT Visit. Also, in the table “NOTES” for the EORTC-QLQ-C30
and EQ-5D-5L for these schedules, it was added that these assessments
may be conducted by telephone during the Follow-up Phase and that
during this phase the assessment is conducted until the start of subsequent
anticancer therapy. In addition, the order in which the PRO assessments
should be conducted was clarified, ie, Patient Global Impression of
Symptom Severity (PGIS), PGIC, EORTC-QLQ-C30, and EQ-5D-5L.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
149
Status: Approved, Date: 22 February 2023
Rationale: Highlighted the need to submit tumor tissue and clarified the use of tissue samples when local FGFR
testing is utilized. Additional instruction regarding molecular testing was provided in Section 8.1.1.1.
1.3. Schedule of Activities: For 
Adults . . .; 
1.4. Schedule of Activities: For 
Adolescents . . .; 
8.1.1.1. Molecular Eligibility 
Screening Period; 
Figure 3 
In the “Local FGFR results . . . “ row of each Schedule of Activities, the
section bullet was revised to state: “Tumor tissue must be submitted.*
See ‘Tumor Tissue for Molecular Eligibility, Biomarker Research, and/or
Companion Diagnostic Development’. Also, the last sentence was
revised to state: “*If tissue is not available [this phrase was removed here
‘for central confirmation’], please contact the sponsor prior to proceeding
with full-study screening.” Small edits were made to the Adolescent
Schedule of Activities so that that row is identical to the adult entry.
Cross-reference to Tumor Tissue for Molecular Eligibility, Biomarker
Research, and/or Companion Diagnostic Development was added to the
NOTE for the row “Central Molecular Eligibility Testing from Tissue”.
In the Schedules of Activities, the row title “Tumor tissue for biomarker
research” was lengthened by adding “for molecular eligibility…and/or
companion diagnostics development”. The original text was replaced
with the following: “Tumor tissue must be submitted.* Samples will be
used for any or all of the following purposes: molecular eligibility for
study eligibility (Central Screening); biomarker research; diagnostic
development; central confirmation of local FGFR testing results (if
applicable). This row is newly added to Section 1.4.
*If tissue is not available, please contact the sponsor prior to proceeding
with full-study screening”.
In Section 8.1.1.1, the first sentence of Part 2a has been revised to 1)
include biomarker research, 2) add (where applicable), and 3) remove
timing of submission. The first sentence now states: “If a subject is
enrolled based on local testing, a tissue sample must be submitted for:
retrospective confirmation of FGFRa status (where applicable);
diagnostic development; biomarker research.” The remaining portion of
Section “a” was added as a footnote at the bottom of the page. The first 2
changes were added to Figure 3 in this section.
Rationale: Clarified the timing of the cerebrospinal fluid (CSF) PK and plasma PK samples at the time of a routine
CSF procedure.
1.3. Schedule of Activities: For 
Adults . . .; 
1.4. Schedule of Activities: For 
Adolescents . . .; 
8.5. Pharmacokinetics
It was noted in the referenced sections to the left that CSF PK and plasma
PK samples will be conducted during the Treatment Phase at the time of
a routine CSF procedure (they were previously shown on the Schedule of
activities during this timeframe, but instruction has been added in text.)
Rationale: Slightly revised the laboratory values indicative of bone marrow function in Inclusion Criterion 9 to
align more closely with Inclusion Criterion 7, ie, Grade 2 absolute neutrophil count (ANC) and hemoglobin include
the value 1,000/mm3 and 8.0 g/dL, respectively, and Grade 1 platelet count includes the value 75,000/mm3.
5.1. Inclusion Criteria (Number 9a) 
For Inclusion Criterion 9, revised the inclusion limits for these laboratory
tests as follows (the “>” sign was replaced by the “≥” sign:
- Absolute neutrophil count (ANC) ≥1,000/mm3
- Platelet count ≥75,000/mm3
- Hemoglobin ≥8.0 g/dL

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
150
Status: Approved, Date: 22 February 2023
Rationale: Clarified the timing of the urine or serum β-hCG pregnancy test at screening and thereafter.
1.3. Schedule of Activities: For 
Adults . . .; 
1.4. Schedule of Activities: For 
Adolescents . . .; 
10.2. Appendix 2, Clinical Laboratory 
Tests
Clarified the timing of the pregnancy test at screening on the Schedule of
Activities by adding that the test may be done at C1D1 prior to the first
dose. Also, in Section 10.2, clarified that additional serum or urine
pregnancy tests will be performed on Day 1 of every cycle (starting with
C2D1); the information in parentheses was added.
Rationale: Clarified the meaning of “permanently sterile” in the inclusion criterion regarding contraception per the
protocol template.
5.1. Inclusion Criteria 
The above clarification was added to Inclusion Criterion 12 (now 12.1),
ie,  “[for the purpose of this study]” was added to this criterion so that it
now states: “For females of childbearing potential (defined as: fertile,
following menarche and until becoming post-menopausal unless
permanently sterile [for the purpose of this study]. Permanent sterilization
methods include hysterectomy, bilateral salpingectomy and bilateral
oophorectomy):”.
Rationale: Corrected wording of Exclusion Criterion 11 to remove mention of triplicate measurement, which
makes this criterion now consistent with the Schedule of Activities
5.2. Exclusion Criteria (Number 11) 
Removed the mention of triplicate measurement (not required) for
assessment of QTc prolongation.
Rationale: Use of the Bazett formula for assessment of QTc prolongation in adolescent subjects is allowed.
5.2. Exclusion Criteria (Number 11); 
8.3.3. Electrocardiogram; 
9.4.7. Safety Analyses
(Electrocardiogram)
Optional use of the Bazett formula was added for determination of QTc
prolongation in adolescent subjects was added.
Rationale: Clarified when Tanner Staging is discontinued. The Tanner Staging chart was removed to simplify the
protocol, as it is deemed a routine assessment.
1.4. Schedule of Activities: For 
Adolescents . . .; 
8.3.1. Physical Examinations; 
10.11. Appendix 11, Sexual Maturity
Rating . . .
Noted that Tanner Staging is discontinued when a subject turns 18 years
of age. As mentioned above, the Tanner Staging chart was removed from
Section 10.11.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
151
Status: Approved, Date: 22 February 2023
Rationale: Minor errors, editorial issues, or changes for clarity/consistency were noted and corrected.
1.3. Schedule of Activities: For 
Adults . . .; 
1.4. Schedule of Activities: For 
Adolescents . . .; 
2.2.3. Fibroblast Growth Factor . . . 
6.6.1.6. Guidelines . . . ; 
8.2.1.1 RECIST and RANO…  
8.2.1.2. Radiographic Images 
Assessment; 
8.2.2. Continuation of Treatment…; 
8.3.7. Bone-related Assessments 
(Adolescents); 
8.6. Biomarkers;
8.7. Patient Report Outcomes;
9.4.4. Pharmacokinetic and
Pharmacokinetic/Pharmacodynamic…  
10.6. Appendix 6; 
11. References 
On the Schedule of Activities, added a row for the Investigator RECIST
or RANO Assessment (abbreviations added to table lists), and added
subheaders for “Patient Reported Outcome Assessments”, and “PK and
Biomarker Assessments”. Added that the visit window that applies to C2
also applies to C3, by addition “C3” to the table header. On the Adult
Schedule of Activities after the text “Fresh tumor biopsy . . . ” added
“(Paired biopsies)” as this fresh tumor biopsy is referred to as such in the
body of the protocol; the biomarker section (Section 8.6) was referenced.
Aligned footnote d in Section 1.3 and footnote e in Section 1.4 with
scheduled timepoints in the Schedule of Activities.
Requirements for radiographic assessments were clarified in Section 1.4,
Section 8.2.1.2, and Section 8.3.7.
Text in Section 8.2.1.1 revised to indicate that RANO criteria will be used
to assess response to treatment for subjects with primary CNS tumors.
Corrected 
the 
Phase 
2 
Study 
noted 
in 
Section 
8.6 
to
JNJ42756493BLC2001 (deleted JNJ42756493EDI1001). Removed
small amount of text in strike-out font in Section 6.6.1.6. In Section 8.2.2,
a sentence was added noting ECOG, Karnofsky, Lansky performance
score comparison chart is provided in Section 10.6. Text reordered and
references added for the EORTC-QLQ-C30 in Section 8.7; citations were
added to the reference list in Section 11. The heading in Section 9.4.4 was
updated. Clarification added to Appendix 6 indicating the ages at which
the Karnofsky and Lansky scales are used. In the reference list, added
mention of CGI to Reference 17, revised access date for Reference 28,
and added References 25, 31, and 34. The genomic databases were
referenced in Section 2.2.3.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
152
Status: Approved, Date: 22 February 2023
11. 
REFERENCES
Adeli K, Higgins V, Nieuwesteeg M, et al. Biochemical marker reference values across pediatric, adult, and geriatric
ages: establishment of robust pediatric and adult reference intervals on the basis of the Canadian Health Measures
Survey. Clin Chem. 2015;61(8):1049-1062.
American Red Cross. Available at: http://www.redcrossblood.org/learn-about-blood/blood-facts-and-statistics.
Accessed 29 March 2019.
Babina IS and Turner NC. Advances and challenges in targeting FGFR signalling in cancer. Nat Rev Cancer.
2017;17(5):318-332.
Berry SM, Broglio KR, Groshen S, Berry DA. Bayesian hierarchical modeling patient subpopulations: Efficient
designs of Phase II oncology clinical trials. Clin Trials. 2013;10:720-734.
Blethen SL and Rundle AC. Slipped capital femoral epiphysis in children treated with growth hormone. A summary
of the National Cooperative Growth Study experience. Horm Res. 1996;46(3):113.
Cancer Hotspots [Database] (A resource for statistically significant mutations in cancer). Memorial Sloan Kettering
Cancer Center. Available at: http://www.cancerhotspots.org/#/home. Accessed 10 June 2019.
Chakravarty D, Gao J, Phillips SM, et al. OncoKB: A Precision Oncology Knowledge Base. JCO Precis Oncol 2017.
DOI: 10.1200/PO.17.00011 Published online 16 May 2017.
Chang MT. Accelerating discovery of functional mutant alleles in cancer. Cancer Discov. 2018;8(2):174-183.
Chen YY, Park JO, Su WC, et al. Preliminary results of a Ph2a study to evaluate the clinical efficacy and safety of
erdafitinib in Asian patients with biomarker-selected advanced cholangiocarcinoma (CCA). (European Society for
Medical Oncology Poster) Ann Oncol. 2018;29(8). doi: 10.1093/annonc/mdy282.008.
Chugh R, Wathen JK, Maki RG, et al. Phase II multicenter trial of imatinib in 10 histological subtypes of sarcoma
using a Bayesian hierarchical statistical model. J Clin Oncol. 2009;27(19):3148-3153.
de Andrade AC, Longui CA, Damasceno FL, Santili C. Southwick's angle determination during growth hormone
treatment and its usefulness to evaluate risk of epiphysiolysis. J Pediatr Orthop B. 2009;18(1):11-15.
Deng C, et al. Fibroblast Growth Factor Receptor 3 Is a Negative Regulator of Bone Growth. Cell,
1996;84(6):911-921.
Dienstmann R, Rodon J, Prat A, et al. Genomic aberrations in the FGFR pathway: opportunities for targeted therapies
in solid tumors. Ann Oncol. 2014;25(3):552-563.
EMA. Ethical considerations for clinical trials on medicinal products with the paediatric population.
http://ec.europa.eu/health/files/eudralex/vol-10/ethical_considerations_en.pdf. Section 13.2, Volume of Blood.
Accessed 29 March 2019.
eProvide: Online support for clinical outcome assessment. Patient Global Impression of Change (PGIC).
https://eprovide.mapi-trust.org/instruments/patient-global-impression-of-change#basic_description. Updated January
2019. Accessed 25 March 2019.
Fathallah-Shaykh S, Drozdz D, Flynn J, et al. Efficacy and safety of sevelamer carbonate in hyperphosphatemic
pediatric patients with chronic kidney disease. Pediatr Nephrol. 2018;33:325–333.
Ferris RL, Blumenschein G, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck.
N Engl J Med. 2016;375:1856-1867.
Foundation 
Insights™ 
[genomic 
database]. 
Foundation 
Medicine. 
Available 
at:
https://www.foundationmedicine.com/insights-and-trials/foundation-insights. Accessed 10 June 2019.
Friedman HS, Prados, MD, Wen PY, et al. Bevacizumab alone and in combination with irinotecan in recurrent
glioblastoma. J Clin Oncol. 2009;27:4733-4740.
Gröbner SN, Worst BC, Weischenfeldt J, et al. The landscape of genomic alterations across childhood cancers. Nature.
2018 Mar 15;555(7696):321-327.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
153
Status: Approved, Date: 22 February 2023
Guy W (ed). ECDEU Assessment Manual for Psychopharmacology. CGI Global Clinical Impressions. Rockville,
MD: US Department of Health, Education, and Welfare Public Health Service Alcohol, Drug Abuse, and Mental
Health Administration, 1976.
Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of EQ-5D
(EQ-5D-5L). Qual Life Res. 2011;20(10):1727-1736.
Howie SR, Blood sample volumes in child health research: review of safe limits. Bull World Health Organ.
2011;89:46-53.
Katoh, M. Fibroblast growth factor receptors as treatment targets in clinical oncology. Nat Rev Clin Oncology.
2019;16(2):105-122.
Kay RM and Kim Y. Chapter 25- Slipped Capital femoral epiphysis. Lowell and Winters Pediatric Orthopedics, 7th
edition. 2014. 1165-1221.
Knowles MA, Hurst CD. Molecular biology ofbladder cancer: new insights into pathogenesis and clinical diversity.
Nat Rev Cancer. 2015;15(1):25-41.
Michelson H, Bolund C, Nilsson B, Brandberg Y. Health-related quality of life measured by the EORTC QLQ-C30:
Reference values from a large sample of the Swedish population. Acta Oncol. 2000;39(4):477-484.
Nasreddine AY, Heyworth BE, Zurakowski D, Kocher MS. A reduction in body mass index lowers risk for bilateral
slipped capital femoral epiphysis. Clin Orthop Relat Res. 2013;471(7):2137-2144.
OncoKB Precision Oncology Knowledge Base. Memorial Sloan Kettering Cancer Center. Available at:
http://www.oncokb.org/. Site updated 09 May 2019. Accessed 10 June 2019.
[Project] Genomics Evidence Neoplasia Information Exchange (GENIE) Database. American Association for Cancer
Research. Available at: http://www.aacr.org /Research/Research/pages/accr-project-genie.aspx. Accessed February
2019.
Parker BC, Engels M, Annala M, Zhang W. Emergence of FGFR family gene fusions as therapeutic targets in a wide
spectrum of solid tumours. J Pathol. 2014;232(1):4-15.
Parsons DW, Janeway KA, Patton D, et al. Identification of targetable molecular alterations in the NCI-COG Pediatric
MATCH trial. J Clin Oncol. 2019;37:15_suppl; abstr 10011.
Pediatric 
Functional 
Assessment Of 
Cancer 
Therapy 
- 
Brain 
(Peds 
FACT-Br). 
Available 
at:
https://www.facit.org/measures/peds-FACT-BR. Accessed July 2021.
Peck DM, Voss LM, Voss TT. Slipped Capital Femoral Epiphysis: Diagnosis and Management. Am Fam Physician.
2017;95(12):779-784.
Schmidtt CP and Mehls O. Chapter 50-Disorders of Bone Mineral Metabolism in Chronic Kidney Disease.
Comprehensive Pediatric Nephrology. 2008, 773-792.
Schwarz R, Hinz A. The Reference data for the quality of life questionnaire EORTC QLQ-C30 in the General German
population. Euro J Cancer. 2001;37(11):1345-1351.
Spiessens B, Debois M. Adjusted significance levels for subgroup analysis in clinical trials. Contemporary Clin Trials.
2010;31:647-656.
The 
Cancer 
Genome 
Atlas 
Program 
(TCGA). 
NIH: 
National 
Cancer 
Institute. 
Available 
at:
https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga. Accessed February 2019.
Touat M, Ileana E, Postel-Vinay S, André F, Soria JC. Targeting FGFR signaling in cancer. Clin Cancer Res.
2015;21(12):2684-2694.
van den Bent MJ, Wefel J, Taphoorn MJ, et al. Response assessment in neuro-oncology (a report of the RANO group):
assessment of outcome in trials of diffuse low-grade gliomas. Lancet Oncol. 2011 Jun;12(6):583-93. doi:
10.1016/S1470-2045(11)70057-2. Epub 2011 Apr 5.
Veal GJ. Blood volumes in pediatric clinical trials: a review of current regulations and guidance for research studies.
Clin Invest (Lond). 2014;4(11):1005-1011.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
154
Status: Approved, Date: 22 February 2023
Walker SJ, Whiteside LA, McAlister WH, Silverman CL, Thomas PR. Slipped capital femoral epiphysis following
radiation and chemotherapy. Clin Orthop Relat Res. 1981;(159):186-193.
Wen PY, Macdonald DR, Reardon DA, et al. Updated response assessment criteria for high-grade gliomas: response
assessment in neuro-oncology working group. J Clin Oncol. 2010;28:1963-1972.

JNJ-42756493  (erdafitinib)
Clinical Protocol 42756493CAN2002  Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
155
Status: Approved, Date: 22 February 2023
INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully informed
regarding the study intervention, the conduct of the study, and the obligations of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature: 
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature: 
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer:
Name (typed or printed): 
Institution: 
Janssen Research & Development
Signature: electronic signature appended at the end of the protocol 
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the study, written notification will be
provided by the investigator to the sponsor, and a protocol amendment will not be required.
PPD

Signature
User 
Date 
Reason
 
 
23-Feb-2023
13:22:35
(GMT)
Document Approval
PPD
PPD

CONFIDENTIAL – FOIA Exemptions Apply in U.S.
1
Status: Approved,  Date: 08 June 2020
Janssen Research & Development *
Clinical Protocol
COVID-19 Appendix
A Phase 2 Study of Erdafitinib in Subjects with  Advanced Solid Tumors and FGFR Gene 
Alterations
Protocol 42756493CAN2002; Phase 2
JNJ-42756493  (erdafitinib)
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries. Therefore, the legal entity acting as the sponsor for Janssen Research & Development
studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; Janssen Biologics,
BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Pharmaceutica NV; Janssen Sciences Ireland
UC; Janssen Biopharma Inc.; or Janssen Research & Development, LLC. The term “sponsor” is used
throughout the protocol to represent these various legal entities; the sponsor is identified on the Contact
Information page that accompanies the protocol.
United States (US) sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).
EudraCT NUMBER:    2019-002113-19     
Status:
Approved  
Date:
08 June 2020
Prepared by:
Janssen Research & Development, LLC
EDMS number:
EDMS-RIM-83679, 1.0
THIS APPENDIX APPLIES TO ALL CURRENT APPROVED VERSIONS OF 
PROTOCOL 42756493CAN2002 (EDMS-ERI-179740920)
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company 
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise.
NCT04083976

COVID-19 Appendix
JNJ-42756493 (erdafitinib)
Clinical Protocol 42756493CAN2002
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
2
Status: Approved,  Date: 08 June 2020
COVID-19 APPENDIX
GUIDANCE ON STUDY CONDUCT DURING A NATIONAL DISASTER FOR 
ENROLLED SUBJECTS
It is recognized that a national disaster, eg, pandemic, may have an impact on the conduct of this 
clinical study. In alignment with the recent health authority guidances, the Sponsor is providing 
guidance for study-related patient management in the event of disruption to the per-protocol 
conduct of the study as outlined throughout the protocol. These measures are to be followed on a 
temporary basis. Once the national situation allows, the usual study conduct methods will resume. 
This guidance does not supersede any local or government requirements or the clinical judgement
of the Investigator to protect the health and well-being of patients and site staff. If at any time a 
subject’s safety is considered to be at risk, study drug will be discontinued, and study follow-up 
will be conducted, as outlined in the protocol. (Note: These measures do not apply to subjects who 
have not initiated study treatment.)
Scheduled visits for safety monitoring and other protocol required assessments that cannot be 
conducted in-person will be performed remotely/virtually (eg, telephone contact, telemedicine, 
remote nursing, remote administration of study drug), where feasible, or delayed until the time at 
which access is determined to be appropriate by the Investigator and Sponsor. Study assessments 
requiring investigator judgement, should be conducted by the investigator. At each contact, 
subjects will be interviewed to collect adverse events data and any changes to concomitant 
medications. Subjects will also be questioned regarding general health status to fulfill the physical 
examination requirement. 
Flexibility for all protocol-required assessments will be provided on a case by case basis, and with 
agreement between the Sponsor and Investigator. However, every effort should be made to adhere 
to protocol-specified assessments, including follow-up, if it is in the best interest of the subject. 
The Sponsor will continue to monitor the conduct and progress of the clinical study and any 
changes (eg, delay or discontinuation in recruitment) will be communicated to the sites and health 
authorities.  
Guidance specific to this protocol:

Missed assessments or change to protocol assessments will be documented in the source 
documentation and in the case report form. All study conduct performed outside of the 
protocol should be documented in the source documentation. 

If a site visit is not feasible, the Investigator may discuss with the Sponsor other 
mechanisms for the subject to receive study drug (eg, direct to patient shipment, obtain 
from another Investigative Site participating in the study).  Any change in dispensing study 
drug must be documented in the source documentation and eCRF. 

Safety assessments may be conducted at a local facility after discussion with the Sponsor.  

COVID-19 Appendix
JNJ-42756493 (erdafitinib)
Clinical Protocol 42756493CAN2002
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
3
Status: Approved,  Date: 08 June 2020

Critical laboratory tests, imaging or other diagnostic tests may be done at an 
authorized/certified (as legally required nationally) local laboratory or clinical facility. A 
copy of the laboratory report must be reviewed by the Investigator and retained, along with 
the reference ranges, for the source documentation and provided with the eCRF.

Consenting of subjects for full study screening and for molecular eligibility screening will 
be performed as applicable (including also remote consenting by telephone or video 
consultation) according to local guidance for the informed consent.