A Phase 3 Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Subjects With Advanced Urothelial Cancer and Selected FGFR Gene Aberrations
Phase: PHASE3
Conditions: Urothelial Cancer
Sponsor: Janssen Research & Development, LLC

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Status: Approved, Date: 20 January 2023
Janssen Research & Development *
Clinical Protocol
A Phase 3 Study of Erdafitinib Compared with Vinflunine or Docetaxel or Pembrolizumab
in Subjects with Advanced Urothelial Cancer and Selected FGFR Gene Aberrations
Protocol 42756493BLC3001; Phase 3
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.
US sites of this study will be conducted under US Food & Drug Administration IND regulations
(21 CFR Part 312).
EudraCT NUMBER: 2017-002932-18
Status: 
Approved
Date: 
20 January 2023
Prepared by: Janssen Research & Development, LLC
EDMS number: 
EDMS-ERI-148605286, 7.0
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.
NCT03390504

JNJ-42756493 (erdafitinib)
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Status: Approved, Date: 20 January 2023
TABLE OF CONTENTS
TABLE OF CONTENTS............................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 5
LIST OF TABLES......................................................................................................................................... 5
LIST OF FIGURES....................................................................................................................................... 5
PROTOCOL AMENDMENTS....................................................................................................................... 6
SYNOPSIS.................................................................................................................................................. 28
TIME AND EVENTS SCHEDULE .............................................................................................................. 31
ABBREVIATIONS...................................................................................................................................... 35
1. 
INTRODUCTION................................................................................................................................ 37
1.1. 
Bladder Cancer.............................................................................................................................. 37
1.2. 
Second-line Chemotherapy........................................................................................................... 37
1.2.1. 
Docetaxel.................................................................................................................................... 37
1.2.2. 
Vinflunine .................................................................................................................................... 38
1.3. 
Immunotherapy.............................................................................................................................. 38
1.3.1. 
Pembrolizumab........................................................................................................................... 39
1.4. 
Fibroblast Growth Factor Receptors and Erdafitinib...................................................................... 39
1.4.1. 
Fibroblast Growth Factor Receptors........................................................................................... 39
1.4.2. 
Erdafitinib.................................................................................................................................... 40
1.5. 
Overall Rationale for the Study...................................................................................................... 41
2. 
OBJECTIVE, ENDPOINTS, AND HYPOTHESES............................................................................ 41
2.1. 
Objectives and Endpoints .............................................................................................................. 41
2.1.1. 
Objectives ................................................................................................................................... 41
2.1.2. 
Endpoints.................................................................................................................................... 42
2.2. 
Hypothesis ..................................................................................................................................... 43
3. 
STUDY DESIGN AND RATIONALE................................................................................................. 44
3.1. 
Overview of Study Design.............................................................................................................. 44
3.2. 
Study Design Rationale.................................................................................................................. 46
3.2.1. 
Choice of Comparators............................................................................................................... 46
3.2.2. 
Two-cohort Design...................................................................................................................... 46
3.2.3. 
Dosing Schedule for Erdafitinib .................................................................................................. 48
3.2.4. 
Blinding, Control, Study Phase/Periods, Treatment Groups ...................................................... 49
3.2.5. 
Biomarker Collection................................................................................................................... 49
3.2.6. 
Patient Reported Outcomes Research....................................................................................... 50
4. 
SUBJECT POPULATION.................................................................................................................. 50
4.1. 
Inclusion Criteria ............................................................................................................................ 50
4.2. 
Exclusion Criteria ........................................................................................................................... 53
4.2.1. 
Exclusion Criteria for All Subjects............................................................................................... 53
4.2.2. 
Exclusion Criteria for Cohort 1 Subjects..................................................................................... 55
4.2.3. 
Exclusion Criteria for Cohort 2 Subjects..................................................................................... 55
5. 
TREATMENT ALLOCATION AND BLINDING................................................................................. 56
6. 
DOSAGE AND ADMINISTRATION .................................................................................................. 56
6.1. 
Erdafitinib ....................................................................................................................................... 56
6.1.1. 
Dose Modifications and Dose Delays for Erdafitinib .................................................................. 57

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6.1.2. 
Guidance for Specific Erdafitinib Toxicities ................................................................................ 59
6.2. 
Vinflunine or Docetaxel .................................................................................................................. 66
6.2.1. 
Vinflunine .................................................................................................................................... 66
6.2.2. 
Docetaxel.................................................................................................................................... 68
6.3. 
Pembrolizumab .............................................................................................................................. 70
6.3.1. 
Pembrolizumab Dose Modifications ........................................................................................... 71
6.4. 
Continued Access to Study Drug after the End of Data Collection Timepoint............................... 71
7. 
TREATMENT COMPLIANCE............................................................................................................ 72
8. 
CONCOMITANT THERAPY.............................................................................................................. 72
8.1. 
Permitted Medications.................................................................................................................... 72
8.2. 
Prohibited Medications................................................................................................................... 73
8.3. 
Precautions for Concomitant Medications ..................................................................................... 73
9. 
STUDY EVALUATIONS.................................................................................................................... 74
9.1. 
Study Procedures........................................................................................................................... 74
9.1.1. 
Overview..................................................................................................................................... 74
9.1.2. 
Screening Phase ........................................................................................................................ 74
9.1.3. 
Treatment Phase ........................................................................................................................ 76
9.1.4. 
Follow-Up Phase ........................................................................................................................ 76
9.2. 
Efficacy Evaluations....................................................................................................................... 77
9.2.1. 
Evaluations ................................................................................................................................. 77
9.2.2. 
Continuation of Treatment After Disease Progression ............................................................... 78
9.3. 
Pharmacokinetics........................................................................................................................... 78
9.3.1. 
Analytical Procedures................................................................................................................. 78
9.4. 
Predictive and Pharmacodynamic Biomarkers .............................................................................. 78
9.5. 
Patient Reported Outcomes........................................................................................................... 81
9.6. 
Medical Resource Utilization.......................................................................................................... 82
9.7. 
Safety Evaluations ......................................................................................................................... 82
9.7.1. 
Adverse Events........................................................................................................................... 82
9.7.2. 
Clinical Laboratory Tests ............................................................................................................ 83
9.7.3. 
Renal Toxicity Evaluation ........................................................................................................... 83
9.7.4. 
Urine or Serum Beta-hCG Pregnancy Test................................................................................ 84
9.7.5. 
Electrocardiogram....................................................................................................................... 84
9.7.6. 
Ophthalmologic Examination...................................................................................................... 84
9.7.7. 
Vital Signs................................................................................................................................... 85
9.7.8. 
Physical Examination.................................................................................................................. 85
9.7.9. 
ECOG Performance Status ........................................................................................................ 85
9.8. 
Sample Collection and Handling.................................................................................................... 85
10. SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ WITHDRAWAL
FROM THE STUDY........................................................................................................................... 85
10.1. 
Completion ..................................................................................................................................... 85
10.2. 
Discontinuation of Study Treatment/Withdrawal From the Study.................................................. 86
10.3. 
Withdrawal from the Use of Research Samples ............................................................................ 87
11. STATISTICAL METHODS................................................................................................................. 87
11.1. 
Subject Information ........................................................................................................................ 87
11.2. 
Sample Size Determination ........................................................................................................... 87
11.3. 
Efficacy Analyses........................................................................................................................... 88
11.3.1. 
Primary Endpoint ........................................................................................................................ 88
11.3.2. 
Secondary Efficacy Endpoints.................................................................................................... 88
11.3.3. 
Subgroup Analyses..................................................................................................................... 89
11.3.4. 
Baseline Assessments................................................................................................................ 89
11.4. 
Pharmacokinetic and Pharmacokinetic/Pharmacodynamic Analyses ........................................... 89
11.5. 
Biomarker Analyses ....................................................................................................................... 89
11.6. 
Medical Resource Utilization and Patient Reported Outcomes Analyses ..................................... 90

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11.7. 
Safety Analyses ............................................................................................................................. 90
11.8. 
Interim Analysis.............................................................................................................................. 92
11.9. 
Independent Data Monitoring Committee ...................................................................................... 92
12. ADVERSE EVENT REPORTING ...................................................................................................... 92
12.1. 
Definitions ...................................................................................................................................... 93
12.1.1. 
Adverse Event Definitions and Classifications ........................................................................... 93
12.1.2. 
Attribution Definitions.................................................................................................................. 94
12.1.3. 
Severity Criteria .......................................................................................................................... 94
12.2. 
Special Reporting Situations.......................................................................................................... 95
12.3. 
Procedures..................................................................................................................................... 95
12.3.1. 
All Adverse Events...................................................................................................................... 95
12.3.2. 
Serious Adverse Events ............................................................................................................. 96
12.3.3. 
Pregnancy................................................................................................................................... 98
12.3.4. 
Disease-related Events and Disease-related Outcomes Not Qualifying as Adverse
Events or Serious Adverse Events ............................................................................................. 98
12.4. 
Contacting Sponsor Regarding Safety........................................................................................... 98
13. PRODUCT QUALITY COMPLAINT HANDLING.............................................................................. 98
13.1. 
Procedures..................................................................................................................................... 99
13.2. 
Contacting Sponsor Regarding Product Quality............................................................................ 99
14. STUDY DRUG INFORMATION......................................................................................................... 99
14.1. 
Physical Description of Study Drug(s)........................................................................................... 99
14.2. 
Packaging ...................................................................................................................................... 99
14.3. 
Labeling.......................................................................................................................................... 99
14.4. 
Preparation, Handling, and Storage............................................................................................. 100
14.5. 
Drug Accountability...................................................................................................................... 100
15. STUDY-SPECIFIC MATERIALS..................................................................................................... 100
16. ETHICAL ASPECTS....................................................................................................................... 101
16.1. 
Study-Specific Design Considerations......................................................................................... 101
16.2. 
Regulatory Ethics Compliance..................................................................................................... 102
16.2.1. 
Investigator Responsibilities ..................................................................................................... 102
16.2.2. 
Independent Ethics Committee or Institutional Review Board ................................................. 102
16.2.3. 
Informed Consent ..................................................................................................................... 103
16.2.4. 
Privacy of Personal Data .......................................................................................................... 104
16.2.5. 
Long-Term Retention of Samples for Additional Future Research .......................................... 105
16.2.6. 
Country/Territory Selection....................................................................................................... 105
17. ADMINISTRATIVE REQUIREMENTS............................................................................................ 105
17.1. 
Protocol Amendments.................................................................................................................. 105
17.2. 
Regulatory Documentation .......................................................................................................... 106
17.2.1. 
Regulatory Approval/Notification .............................................................................................. 106
17.2.2. 
Required Prestudy Documentation........................................................................................... 106
17.3. 
Subject Identification, Enrollment, and Screening Logs .............................................................. 107
17.4. 
Source Documentation................................................................................................................. 107
17.5. 
Case Report Form Completion .................................................................................................... 108
17.6. 
Data Quality Assurance/Quality Control ...................................................................................... 108
17.7. 
Record Retention ......................................................................................................................... 109
17.8. 
Monitoring .................................................................................................................................... 109
17.9. 
Study Completion/Termination..................................................................................................... 110
17.9.1. 
Study Completion (ie, End of Data Collection Timepoint) and End of Study........................... 110
17.9.2. 
Study Termination..................................................................................................................... 110
17.10. On-Site Audits.............................................................................................................................. 111
17.11. Use of Information and Publication .............................................................................................. 111

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Status: Approved, Date: 20 January 2023
REFERENCES.......................................................................................................................................... 113
INVESTIGATOR AGREEMENT............................................................................................................... 127
LIST OF ATTACHMENTS
Attachment 1: 
ECOG Performance Status.......................................................................................... 115
Attachment 2: 
Cockcroft-Gault Formula for Estimated Creatinine Clearance .................................... 116
Attachment 3: 
The Stages of Heart Failure –New York Heart Association (NYHA)
Classification................................................................................................................ 117
Attachment 4: 
Amsler Grid .................................................................................................................. 118
Attachment 5: 
Drugs Classified as Strong or Moderate in Vivo Inhibitors and Inducers of
CYP3A4/2C9 Enzymes................................................................................................ 119
Attachment 6: 
Anticipated Events ....................................................................................................... 120
Attachment 7: 
Guidance on Study Conduct for Enrolled Subjects During a National Disaster.......... 122
Attachment 8: 
Long-Term Extension Phase with Potential Cross-over to Erdafitinib......................... 124
LIST OF TABLES
Table 1: 
Erdafitinib Dose Modification Rules Based on Erdafitinib-related Toxicity............................... 58
Table 2: 
Erdafitinib Dose Reduction Levels............................................................................................ 59
Table 3: 
Grading of Hyperphosphatemia................................................................................................ 59
Table 4: 
Guidelines for Management of Serum Phosphate Elevation.................................................... 59
Table 5: 
Guidelines for Management of Dry Mouth (Xerostomia) ................................................................ 61
Table 6: 
Guidelines for the Management of Oral Mucositis.................................................................... 61
Table 7: 
Guidelines for Management of Dry Skin................................................................................... 62
Table 8: 
Guidelines for Management of Nail Discoloration/Loss/Ridging (Onycholysis/
Onychodystrophy)..................................................................................................................... 63
Table 9: 
Guidelines for Management of Paronychia .............................................................................. 64
Table 10: Guidelines for Management of Eye Toxicity............................................................................. 65
Table 11: Vinflunine Dose Adjustments for Drug-related Adverse Events ............................................... 68
Table 12: Docetaxel Dose Modifications for Drug-related Adverse Events.............................................. 70
LIST OF FIGURES
Figure 1: Schematic Overview of the Study............................................................................................. 45

JNJ-42756493 (erdafitinib)
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Status: Approved, Date: 20 January 2023
PROTOCOL AMENDMENTS
Protocol Version 
Issue Date
Original Protocol 
29 Sep 2017
Amendment 1 
26 Oct 2017
Amendment 2 
01 May 2018
Amendment 3 
18 Jan 2019
Amendment 4 
29 Mar 2020
Amendment 5 
25 March 2021
Amendment 6 
20 January 2023
Amendments below are listed beginning with the most recent amendment.
Amendment 6 (20 January 2023)
The overall reason for the amendment: To add the Long-term Extension (LTE) Phase. The addition
of the LTE Phase modifies the overall end of study definition. Study completion is distinct from end of
study. Study completion is defined as the end-of-data-collection timepoint for both cohorts, which is
defined as when the clinical cutoff at for the final analysis has been achieved.  End of study is defined as
when the last subject receives the last dose of study drug on the study.
Applicable Section(s) 
Description of Change(s)
Rationale: To add the LTE Phase, which modifies the “study completion” and “end of study” definitions,
as noted above.
Synopsis (Overview of 
Study Design); 
Time and Events 
Schedule; 3.1. Overview 
of Study Design;
6.4. Continued Access to 
Study Drug after the End 
of Study Data Collection; 
Timepoint; 
9.1.3. Treatment Phase; 
9.1.4. Follow-Up Phase; 
9.7.1. Adverse Events; 
10.1. Completion; 
17.9.1. Study Completion 
(ie, End of Data Collection 
Timepoint) and End of 
Study;
Attachment 8
The LTE Phase was added to the protocol with Attachment 8, which includes
a Time and Events Schedule. The LTE Phase is also mentioned in the
synopsis and body of the protocol. Attachment 8 also adds that the Sponsor
may decide to allow cross-over to erdafitinib at this time.
The LTE Phase begins with the approval of Amendment 6 and with
achievement of the clinical cut-off for the final analysis for each cohort. (For
Cohort 1, the Sponsor will notify the investigators if the interim analysis will
be considered the final analysis.) Upon initiation of the LTE Phase, the
follow up of subjects will end and the eCRF will be closed. Subjects in the
respective cohort who are continuing to derive benefit from study drug, as
determined by their investigator may have continued access to study drug.
This continued access to study drug could be either in the LTE Phase of this
study, or, alternatively, subjects may exit the study and continue to receive
treatment on any other post-trial access program, when permitted by local
regulations.)
During this LTE Phase (when study drug will be supplied by the Sponsor
after the end of data collection timepoint), only serious adverse events will
be reported to the Company safety repository. (In Adverse Event Section
9.7.1, the reader is also referred to the LTE Phase Attachment.) Clinical
assessments will be conducted according to the standard of practice.
New Section 6.4 was added to describe treatment with erdafitinib,
chemotherapy, and pembrolizumab after the end of data collection time
point.

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Status: Approved, Date: 20 January 2023
Applicable Section(s) 
Description of Change(s)
Section 17.9.1 provides the modified study completion  and end of study
definitions. The study is considered completed at the time of the end-of-data-
collection timepoint for both cohorts. The end-of-data-collection timepoint
is defined as when the clinical cutoff at final analysis has been achieved. At
that time, participation in the Follow-Up Phase will end and the data
collection will conclude. The end of study is defined as when the last subject
receives the last dose of study drug on the study. The Synopsis and Section
17.9.1, as well as the Time and Events Schedule (new Footnote “b”), clarify
the end-of-data-collection timepoint. In Sections 10.1 and 17.9.1, the subject
completion definition has been modified accordingly, ie, 1) died while on
study or 2) not withdrawn by study completion (ie, by the end-of-data-
collection timepoint).
Section 3.1, Overview of Study Design, introduces the LTE Phase in the
body of the protocol and a footnote was added to the study schema to note
the LTE Phase. In this and other sections as applicable, the description of the
Post-treatment Follow-up Phase end point was revised due to the addition of
the LTE Phase (ie, “study completion” rather than “end of study” is used).
Rationale: Replaced comparator drug brand names with the corresponding generic compound names.
1.2.1. Docetaxel; 1.2.2. 
Vinflunine; 1.3.1. 
Pembrolizumab; 14.1. 
Physical Description of
Study Drug(s); 
14.2. Packaging; 
References
Brand names “Taxotere”, “Javlor”, and “Keytruda” were replaced with
respective generic names. Terminologies “SmPC” or “package inserts”
were replaced with “locally available prescribing information”.
Removed summary of product characteristics/prescribing information of
“Taxotere”, “Javlor”, and “Keytruda”  from the list of references.
Rationale: To clarify the length of pembrolizumab treatment in Study KEYNOTE-045.
1.3.1 Pembrolizumab 
The following text was added for Study KEYNOTE-045: “Patients without
disease progression could be treated with pembrolizumab up to 24 months.”
Rationale: To correct the number of core items in the Functional Assessment of Cancer Therapy –
Bladder Cancer (FACT-B1) assessment.
9.5. Patient Reported 
Outcomes 
The number of core items in FACT-B1 was corrected (ie, from 36 to 39
items).
Rationale: To align with the current protocol template.
Attachment 6; 
Throughout the protocol 
Updated Anticipated Event general information in Attachment 6; no change
to the anticipated event terms.
The term “country” was replaced with “country/territory”.
Rationale: Minor clarifications and corrections were made.
Throughout the 
protocol
Minor grammatical corrections and change to abbreviations made throughout.

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Status: Approved, Date: 20 January 2023
Amendment 5 (25 March 2021)
The overall reason for the amendment:
The overall reason for this amendment is to revise the timing of the interim analyses for Cohort 1 and Cohort 2 to
occur at a higher percentage of total events, ie, allow for more mature data. Also, the possible sample size
re-estimation was removed and guidance on the futility boundary was provided.
Applicable Section(s) 
Description of Change(s)
Rationale: The interim analysis for each cohort was revised to occur at a higher percentage of total events, to
ensure that each interim analysis is conducted with more mature data. The sample size re-estimation for each cohort
was removed to complete the study in a reasonable period of time. Also, guidance on the futility boundary was
added to the interim analysis for each cohort.
Synopsis, Overview 
of Study Design; 
Synopsis, Statistical 
Methods; 
3.1, Overview of 
Study Design; 
11.2, Sample Size 
Determination; 
11.3, Efficacy
Analyses;
11.3.1, Primary
Endpoint;
11.3.3, Subgroup 
Analyses; 
11.3.4, Baseline 
Assessments; 
11.8, Interim 
Analysis; 
11.9, Independent 
Data Monitoring 
Committee 
In the Synopsis (Overview of Study Design), the review of the interim analyses by the
Independent Data Monitoring Committee (IDMC) was mentioned. Also, in the Synopsis
(Statistical Methods), the stratification factors for comparison of the survival curves of
OS between the treatment groups were listed.
In Section 11.2, for both Cohort 1 and Cohort 2, the interim analysis is specified as an
efficacy analysis and the percentage information fraction at which each interim analysis
will occur was modified (Cohort 1 at approximately 65% and Cohort 2 at approximately
65%). The number of projected subjects enrolled per site was removed.
In Section 11.3, for the comparison between the 2 treatment arms in each cohort, detail
regarding the continuous and discrete variables was removed. The text regarding separate
analysis of each cohort was moved to the end of this section.
In Section 11.3.1, detail regarding the factors used in the Cox proportional hazards model
for calculating the HR for erdafitinib related to the control was deleted.
New Section 11.3.3 mentions the subgroup analyses for the primary and secondary
efficacy endpoints with reference to the Statistical Analysis Plan (SAP) for further
information. Due to this addition, former Section 11.3.3 is renumbered Section 11.3.4.
In Section 11.8, the timing of the interim analyses was revised to occur when an
approximately 65% information fraction is reached, ie, approximately 136 of 208 deaths
in Cohort 1 and approximately 172 of 264 deaths in Cohort 2. The detail regarding the
statistical software was deleted, as well as the detail regarding interim analysis plan (IAP).
However, the significance level (ie, 0.05) to control the Type 1 error was added.
Additional guidance for the stopping of each cohort due to futility was provided. Some
editing of the main paragraph has occurred for better flow.
In Section 11.9, text regarding IDMC recommendations at the time of the interim analysis
pertaining to the sample size adjustment was deleted, as well as text regarding the
communication of sample size recommendation. It was clarified that the IDMC will
review the interim analysis results for both cohorts. The sentence regarding the safety
review by the IDMC after the first 60 subjects in each cohort was moved from Section
11.8 to Section 11.9, and this sentence was expanded to add the safety reviews every 6
months thereafter.
Rationale: Clarified the liver enzyme (combined with alkaline phosphatase) inclusion criterion for Cohort 1
subjects at sites choosing docetaxel chemotherapy.
4.1, Inclusion Criteria Inclusion criterion 8.3 (now 8.4), the bullet for above mentioned criterion is as follows:
“(For subjects in Cohort 1 at sites choosing docetaxel chemotherapy, both the ALT and
AST values must be ≤1.5×ULN concomitant with alkaline phosphatase of ≤2.5×ULN)”.
Rationale: Live vaccines are not a prohibited medication for patients receiving erdafitinib. The timeframe for
avoidance of live vaccines was revised (ie, more restrictive) for vinflunine, docetaxel, or pembrolizumab.

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Status: Approved, Date: 20 January 2023
Applicable Section(s) 
Description of Change(s)
8.2, Prohibited 
Medications 
The prohibition for receipt of a live vaccine 3 months after the last dose of erdafitinib was
removed. The timeframe for avoidance of a live vaccine for vinflunine and docetaxel was
revised as follows: “Live vaccines within 30 days prior to the first dose and while
participating in the study, [the prior phrase was added] and for 3 months following the last
dose of study therapy.” Also, examples of live vaccines were added. The timeframe for
avoidance of a live vaccine for pembrolizumab was revised as follows: “Live vaccines
within 30 days prior to the first dose and while participating in the study [this last phrase
was added] and for 3 months following the last dose of study therapy.” The examples of
live vaccines previously in this location were deleted as they already appear in the above
text for vinflunine and docetaxel.
Rationale: Clarified the start of the molecular eligibility assessment period when a biopsy is required. In addition,
added that the sponsor must confirm eligibility based on local testing prior to entering full-study screening. Also,
clarified in this section that the Sponsor must confirm eligibility based on local testing prior to entering full study
screening.
9.1.2, Screening 
Phase 
Noted that the molecular eligibility assessment period begins with either the Molecular
Eligibility Testing Informed Consent Form (ICF) or, if a biopsy is required, the Full-Study
ICF.
By Number (2) for the local report, added that the Sponsor must confirm eligibility based
on local testing prior to entering full study screening.
Rationale: Added clarification that subjects on erdafitinib should follow the same visit schedule even when the
drug is interrupted.
9.1.3, Treatment 
Phase
In Section 9.1.3, the above clarification was added to the end of the first paragraph.
Rationale: Instruction for precaution with concomitant medications was updated, ie, the combination of erdafitinib
with moderate CYP2C9 or strong CYP3A inducers should be avoided.
8.3, Precautions for 
Concomitant 
Medications; 
Attachment 5 
The above instruction was added to Section 8.3, along with additional information
regarding erdafitinib and moderate CYP2C9 and strong CYP3A inducers.
In Attachment 5, provided correction to the “Strong CYP3A4 Inhibitor” table, ie, Strong
Inhibitors: ≥5-fold increase in AUC or ≥80 % (previously >80%) decrease in clearance.
Rationale: The prescribing information for pembrolizumab provides the most current information regarding dose
modification.
6.3.1, Pembrolizumab 
Dose Modifications 
The reader is referred to the prescribing information for pembrolizumab and detailed
instruction for dose modification was removed.
Rationale: Clarified the definition of superficial cancer in Inclusion Criterion 5
4.1, Inclusion Criteria Superficial cancer was clarified by adding additional description, ie, “(early disease/non-
muscle invasive bladder cancer)” to Inclusion Criterion 5 (now 5.3). The criterion was
also edited for further clarity.
Rationale: Update guidelines for management of paronychia.

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Applicable Section(s) 
Description of Change(s)
6.1.2.5, Guidelines 
for Management of 
Nail Toxicity
(Onycholysis,
Onychodystrophy,
and Paronychia)
Table 9
In accordance with the National Cancer Institute Common Terminology Criteria for
Adverse Events (NCI-CTCAE) Version 4.03, Grade 4 was removed from Table 9.
Rationale: Aligned wording in several sections with text common to oncology protocols.
12.1.3, Severity 
Criteria; 
12.3.2, Serious 
Adverse Events; 
12.3.4, Disease- 
related Events and 
Disease-related
Outcomes Not
Qualifying as
Adverse Events or
Serious Adverse
Events
In Section 12.1.3, the definitions of Grades 1 to 5 were added (the mild, moderate, and
severe definitions were removed). Also, in Section 12.1.3, the NCI-CTCAE Version was
corrected to 4.03 (was 4.0).
The description of disease-related events (ie, disease progression) was moved from
Section 12.3.2 to a new stand-alone Section 12.3.4, and the text aligned with wording for
oncology protocols.
Rationale: Time Until Symptom Deterioration (subset of the FACT-B1) Patient Reported Outcome (PRO)
assessment was added to more closely evaluate urinary symptoms.
2.1.2, Endpoints; 
11.6, Medical 
Resource Utilization 
and Patient Reported 
Outcomes Analyses 
In Section 2.1.2, change from baseline in Time Until Symptom Deterioration (subset of
the FACT-B1) was added as a secondary endpoint.
In Section 11.6, the hypothesis was changed to “time to urinary symptom deterioration”
(previously “meaningful symptom deterioration”) will be delayed as measured by relevant
items in the FACT-Bl.
Rationale: The description of some of the laboratory tests has been revised to reflect the Time and Events Schedule.
9.1.1, Overview; 
9.7.2, Clinical 
Laboratory Tests 
In Section 9.7.2, the text was revised to reflect serum phosphate, calcium (or, if applicable,
corrected calcium in the case of hypoalbuminemia), albumin, and serum parathyroid
hormone testing per the Time and Events Schedule and to note that these tests are done
for all subjects at screening, but only done for subjects in Arms 1A and 2A after screening.
Also, these specific laboratory tests (ie, albumin, correct calcium, serum calcium,
parathyroid hormone, phosphate) were removed from the list under “Serum Chemistry
Panel”. Updated the blood volume in Section 9.1.1.
Rationale: To provide more options for obtaining consent for molecular eligibility.
Time and Event 
Schedule (footnote); 
Section 9.1.2, 
Screening Phase; 
16.2.3, Informed 
Consent
Added that consent for molecular eligibility screening may be performed remotely
including consent by telephone or video consultation, unless not permitted according to
local guidance.
In Section 16.2.3, noted that informed consent for molecular eligibility may be obtained
remotely.
Rationale: Clarified in the National Disaster attachment that usual study conduct resumes once the national
situation allows and added guidance for consent during a national disaster.

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Applicable Section(s) 
Description of Change(s)
Attachment 7, 
Guidance . . .  During 
a National Disaster 
Added text to the first paragraph to clarify that the measures in this appendix are
temporary and that usual study conduct will resume once the national situation allows.
The following text was added to clarify the consent process during a national disaster:
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.
Rationale: To simplify sample collections during screening, it was clarified that serum phosphate, serum
parathyroid hormone, and calcium and albumin collections, may be collected at Day -14 along with the hematology
and chemistry panels. The collection window for all the clinical laboratory assessments was also provided. In
addition, clarified when corrected calcium is required.
Time and Events 
Schedule 
For serum phosphate, serum parathyroid hormone, and calcium and albumin (under
Chemistry) placed the “X” under the Day -14 column and removed from the Day -30
column (it is acknowledged that this is more restrictive, ie, these draws may no longer be
collected between Day -30 to Day -14). The window for these assessments during the
study was added to each row, ie, may be performed within 2 days prior to Day 1 and Day
14 of each cycle. The window for TSH and FT4 is within 2 days prior to Day 1. For the
calcium [removed “corrected” prior to calcium] and albumin row, added a notation that
corrected calcium is required for hypoalbuminemia.
Rationale: Clarified that no action on the part of the site is required for the “Tumor tissue for [programmed death-
ligand 1] PD-(L)1 and biomarker testing” row on the Time and Event Schedule.
Time and Events 
Schedule 
For the “Tumor tissue for PD-(L)1 and biomarker testing” row that consists of 2 sub rows,
the first row was deleted that pertained to collection at screening until 80 samples have
been obtained from FGFR aberration negative subjects as this has already occurred. In the
second row, the original text was replaced with text regarding no additional sample is
required as PD-(L)1 and biomarker testing is assessed from the tumor tissue (archival or
fresh biopsy) collected at prescreening. The “X” for this row remains unchanged but the
text in parentheses regarding the fresh biopsy was deleted.
Rationale: In the Ethical Aspects section of the protocol, clarified which cohort required prior anti-PD-(L)1 agent
use.
16.1, Study-specific 
Design 
Considerations
In Section 16.1, clarified that Cohort 1 enrolls subjects with prior anti-PD-(L)1 agent use,
and that Cohort 2 enrolls subjects without prior anti-PD-(L)1 agent use.
Rationale: Clarified the timing of disease assessments especially in relation to treatment interruptions.
9.2, Efficacy 
Evaluations 
Clarified the timing of disease assessments by noting that the date of randomization is the
reference point regardless ofinterruptions to treatment.
Rationale: Clarified that the threshold for progressive disease
9.2.2. Continuation of 
Treatment After 
Disease Progression
([added “eg”] eg, ≥20% increase in tumor burden compared to the nadir [previous
baseline])
Rationale: For the timing of radiological assessments, clarified that the starting point is the date of randomization.
Time and Event 
Schedule 
Added that radiological assessments (every 6 weeks, etc.) are calculated from the date of
randomization.

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Applicable Section(s) 
Description of Change(s)
Rationale: A minor correction was made to the guidelines for the management of elevated phosphate levels
(Grade 3) and a clarification was made to the guidelines for the management of elevated phosphate levels (Grades 2
and 3).
Table 4 
For Grades 2 and 3 elevated phosphate levels (Symptom Management), expanded to
include phosphate binders in general and added a notation regarding the information in
the table footnotes regarding phosphate binders other than sevelamer. In addition, a small
correction was added to the Grade 3 “Symptom Management” column that now reads
“ . . . until the serum phosphate level is [previously “returns to”] <7.00 mg/dL.”
Rationale: Minor clarifications and corrections were made.
Throughout the 
protocol; 
Synopsis 
(Hypotheses); 
Time and Events 
Schedule; 
1.4.2, Erdafitinib; 
2.1.1, Objectives; 
2.1.2, Endpoints; 
2.2, Hypothesis; 
11.3.1, Primary 
Endpoint 
The wording regarding prior treatments was clarified by adding “on or”, ie, “must have
progressed on or after 1 or 2 prior line(s)” for Cohort 1 throughout the protocol, except in
the Objective section.
Clarified the wording regarding randomization with the following change: Randomization
to treatment will be within each [“within each” added and “by” removed] cohort.
Section numbers were corrected throughout the protocol.
In the Synopsis (under “Hypotheses”) and Section 2.2, added “prior” to the hypotheses
that now reads “following 1 or 2 prior line(s) of systemic therapy”.
In the Time and Event Schedule, the row related to FGFR testing was renamed “Local
historical [“historical” added] FGFR test results for molecular eligibility.
In Section 1.4.2, removed the reference citation for the Erdafitinib Investigator’s Brochure
(IB) and mention of addenda, which leaves the reader to refer to the most current version
of the IB that includes addenda.
In Sections 2.1.1 and 2.1.2, the objective and endpoint, respectively, related to actigraphy
were removed. Actigraphy was removed with Amendment 4.
In Section 11.3.1, “strata” added to clarify “pre-specified strata combining” to be
implemented when there are too few OS events.
The reference format was updated to the parenthetical style throughout.

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Amendment 4 (29 Mar 2020)
The overall reason for the amendment: To allow subjects to meet appropriate molecular eligibility for the
study by local historical test results for selected FGFR aberrations; ie, subjects can meet molecular eligibility
criteria as determined by central laboratory screening as previously specified, or by local historical test results.
The rationale for and description of changes made during this protocol amendment are provided below. When
changes are provided verbatim, deleted text is shown as strikethrough, and added text is shown as bold font.
Applicable Section(s) 
Description of Change(s)
Rationale: To expedite enrollment, changes to Molecular Screening were implemented to determine a subject’s
eligibility by local historical test results for selected FGFR aberrations, not only by central laboratory testing, as
required previously.
Synopsis, Overview of Study Design; 
Time and Event Schedule; 
3.1, Overview of Study Design, including 
Figure 1; 
4, Subject Population; 
4.1, Inclusion Criteria, Criterion 6; 
9.1.2, Screening Phase 
Specified that a subject’s eligibility can also be determined by local
historical test results for selected FGFR aberrations (ie, molecular
eligibility can be confirmed using either central or local historical
FGFR test results), and that if a subject is enrolled based on local
historical testing, a tissue sample must still be submitted at the time
of enrollment for retrospective confirmation of FGFR status,
diagnostic development, and biomarker research.
Details of acceptable testing methods and tissues suitable for FGFR
testing were added.
Details and rules for central testing and local historical testing were
added.
Rationale: To clarify text for prior anti-PD-(L)1 treatment for Cohort 1, and to update text for Cohort 2.
4.1, Inclusion Criteria, Criterion 5 
Specified that, for Cohort 1, prior treatment with an anti-PD-(L)1
agent can be given as neo-adjuvant, adjuvant, or in metastatic line
of treatment as frontline or maintenance therapy, and added details
of the possible combinations.
Text was revised as shown below for Cohort 2.
Subjects who received neoadjuvant or adjuvant chemotherapy or
immunotherapy and showed disease progression within 12 months
of the last dose are considered to have received systemic therapy in
the metastatic setting.
Rationale: To clarify that the criteria specified for Cohort 1 applies specifically to sites using docetaxel.
4.2.2, Exclusion Criteria for Cohort 1 
Subjects 
Criterion 14 was amended to specify that it was applicable to
participating sites using docetaxel.

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Applicable Section(s) 
Description of Change(s)
Rationale: To allow albumin to be used for calculating corrected calcium levels, and to allow evaluation of the
relationship between calcium, phosphate, and parathyroid hormone, sampling timing for these analytes have been
aligned.
Time and Events Schedule, Clinical 
Laboratory Assessments; 
9.8.2 (previous)/9.7.2 (current), Clinical 
Laboratory Tests 
Additional timepoints for assessment of serum phosphate were
added to the Time and Events Schedule, and parathyroid hormone
was moved to a separate row.
The timepoints for laboratory assessment of parathyroid hormone
was revised. Laboratory assessments for corrected calcium and
albumin were added to the Time and Events Schedule.
The Serum Chemistry Panel was revised to add parathyroid
hormone, albumin, and serum calcium; calcium was revised to
corrected calcium. Specified that bicarbonate testing is only
applicable if the test is locally available.
Rationale: To ensure consistency between the protocol and case report form (CRF) guidelines, harmonize
rounding of phosphate values.
6.1, Erdafitinib, Up-titration Guidelines; 
6.1.2.1, Grading of Hyperphosphatemia, 
Table 3; 
6.1.2.2, Guidelines for the Management of 
Elevated Phosphate Levels, Table 4 
The values for grading of hyperphosphatemia have been revised
throughout the protocol to include 2 decimals, for consistency with
the CRF, and instructions for rounding the second decimal point
were deleted.
Toxicity grades (0 to 4) were added to Table 4.
Rationale: To delete sections describing actigraphy and its analysis, as enrollment in this exploratory substudy
has been low, and the small sample size precludes meaningful analysis.
Time and Events Schedule, Actigraphy 
sub-study; 
9.6, Actigraphy (Selected Sites) (deleted);
9.6.1, Actigraphy-derived Endpoints and
Analyses (deleted);
11.1, Subject Information;
11.7, Actigraphy Endpoints (deleted);
15, Study-Specific Materials
Information related to collecting and analyzing actigraphy was
deleted.
Rationale: 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.
6.1.2.1, Grading of Hyperphosphatemia 
Adverse events related to nails was deleted from Table 3 and from
introductory text to Table 3.
6.1.2.3, Guidelines for the Management of 
Dry Mouth and Mucositis; 
Table 6, Guidelines for the Management
of Oral Mucositis
Updated guidelines for general prophylaxis, as well as for
management of oral mucositis were provided.
6.1.2.5, Guidelines for Management of 
Nail Toxicity (Onycholysis, 
Onychodystrophy, and Paronychia), 
Table 8 and Table 9 
Updated guidelines for management of nail
discoloration/loss/ridging (onycholysis/onychodystrophy) were
provided in Table 8. Definitions of toxicity grade were deleted from
Table 9.

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Applicable Section(s) 
Description of Change(s)
Rationale: To provide the latest available information on cytochrome P450 (CYP) inhibitors and inducers.
8.2, Prohibited Medications; 
8.3, Precautions for Concomitant 
Medications; 
Attachment 5, Drugs Classified as Strong
or Moderate in Vivo Inhibitors and
Inducers of CYP3A4/2C9 Enzymes
Updated information on CYP inhibitors and inducers was provided
to align with currently available information and to revise “strong
CYP2C9 inhibitor” to “moderate CYP2C9 inhibitor”.
Rationale: To clarify instructions related to radiographic image assessments.
9.2.1.2, Radiographic Images Assessment 
Text was revised as shown below.
Computed tomography (CT) scans of the chest, abdomen, pelvis,
and any other location where disease is present will be performed at
Screening, and at each subsequent disease assessment visit.
During the study, disease response will be assessed using CT scans
of the locations of known disease. 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 and lumbar puncture are
required, only if clinically indicated.
Rationale: To add instructions to be followed during a national disaster.
Time and Events Schedule, Footnote a 
(new); 
Attachment 7, Guidance on Study 
Conduct for Enrolled Subjects During a 
National Disaster (new)
A footnote was added to the Time and Events Schedule to refer to
Attachment 7 for guidance on study conduct for enrolled subjects
during a national disaster, and detailed instructions have been
provided in Attachment 7.
Rationale: To revise minor errors or inconsistencies that were noted.
Title page and footer 
Updated confidentiality information was added.
Time and Events Schedule, Tumor tissue 
Text was revised as shown below.
Tumor tissue for central molecular screening
Time and Events Schedule, Radiological 
assessments 
Text was revised as shown below.
Every 6 weeks (±7 days) for 6 months, then every 12 weeks for the
next 6 months (±7 days), then as clinically indicated.
Time and Events Schedule 
A row for protein binding blood sample was added, for consistency
with information provided in Section 9.3.
1.5, Overall Rationale for the Study  
Text was revised as shown below.
Despite the recent improvement in outcomes provided by
compounds targeting the PD-1/PD-L1 pathway, all current
treatment options still have relatively limited clinical activity as
second-line therapy; and there is at the time of initial protocol
development, no targeted therapy was approved for treating
specific subsets of urothelial cancer subjects with FGFR alterations.

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Applicable Section(s) 
Description of Change(s)
4.1, Inclusion Criteria, Criterion 8c 
Text was revised as shown below.
Renal function: Creatinine clearance (CrCl) >30 mL/min/1.73 m2
either directly measured via 24-hour urine collection or calculated
using the Cockcroft-Gault formula (Attachment 2).
6.1.1, Dose Modifications and Dose
Delays for Erdafitinib, Table 1
The title of Table 4 was revised as shown below.
Erdafitinib Dose Modification Rules Based on Erdafitinib-related
Toxicity
6.1.2.6, Guidelines for Eye Toxicity
Associated With Vision Changes
Text was revised as shown below.
If a subject experiences an event of confirmed new corneal or
retinal abnormality while on study drug, the event should be
reported as an adverse event of special interest (if Grade 1 or 2) or a
serious adverse event (if Grade 3 or higher) as appropriate.
9.1.1, Overview  
Text was revised as shown below.
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 maximum amount of blood to be drawn from each subject
is estimated to be 27 22 mL at screening, 266 mL over the course of
the first 6 months (8cycles) of treatment, 22 mL for every cycle
thereafter, and 40 mL at the End-of-Treatment.
9.4, Predictive and Pharmacodynamic 
Biomarkers, Tissue for Immune 
Biomarkers and Molecular Subtyping); 
9.4, Predictive and Pharmacodynamic 
Biomarkers, Circulating Biomarkers, 
Peripheral Immune Cell Profiling
Each of these sections, respectively, was revised as shown below.
At the time of protocol development, it is was estimated that
approximately 80 samples are needed to inform PD-L1 expression
and bladder cancer subtype in FGFR aberration-negative subjects
(see Section 11.5).
T cell and Treg enumeration and T cell activation status will be
assessed at certain sites.
9.5, Patient Reported Outcomes 
Text was revised as shown below.
Patients health-related quality of life, symptoms, functioning, and
general well-being will be captured using 3 PRO measures: the
FACT-Bl, PGIS, and the EQ-5D-5L. The PRO measures will be
collected electronically, if feasible (ePRO) collected, according to
the Time and Events Schedule, to understand change over time and
difference between treatment groups in each cohort.
9.8.5 (previous)/9.7.5 (current), 
Electrocardiogram  
Text was revised as shown below.
Triplicate ECGs should be performed with 5- to 10-minute intervals
between each assessment.
9.8.6 (previous)/9.7.6 (current), 
Ophthalmologic Examination 
Text was revised as shown below.
All images of the OCT scans for enrolled subjects must be stored
in the subject’s records and a redacted copy sent to the sponsor-
selected central vendor for possible future independent assessment.
9.8.7 (previous)/9.7.7 (current), Vital 
Signs 
Text was revised as shown below.
Blood pressure (systolic and diastolic), heart rate, and oral or
tympanic temperature will be assessed. Abnormalities will be
recorded as AEs.

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Applicable Section(s) 
Description of Change(s)
16.1, Study-Specific Design 
Considerations 
Text was revised as shown below.
This is a Phase 3, multicenter, open-label randomized study to
evaluate the efficacy and safety of erdafitinib, an oral pan-FGFR-
inhibitor with pharmacodynamic adaptation of dose (starting dose
of 8 mg once daily with potential up-titration to 9 mg once daily
based on observed phosphate level on Study Day 14) compared to
vinflunine, docetaxel or pembrolizumab in subjects with metastatic
or surgically unresectable urothelial cancer with select FGFR
genetic alterations who progressed on or after one prior line of
systemic therapy 1 or 2 prior treatments (Cohort 1) or 1 prior
treatment (Cohort 2).
Throughout the protocol 
Minor errors and inconsistencies were revised, and grammatical,
formatting, or spelling changes were made. Abbreviations and
references were updated as needed.
Amendment 3 (18 January 2019)
The overall reason for the amendment: To address request from regulatory authorities and to expand the
population eligible for cohort 1, in line with current standard of care.
Applicable Section(s) 
Description of Change(s)
Rationale: To comply with health/regulatory authority requests.
Synopsis; Time and Events 
Schedule; 2.1.1, Objectives; 
2.1.2, Endpoints; 9.4 Predictive and 
Pharmacodynamic Biomarkers; 
11.4, Pharmacokinetic and
Pharmacokinetic/Pharmacodynamic
Analyses
For subjects on erdafitinib (Arms 1A and 2A), added blood sample
collection at Cycle 1 Day 14 (or later time point) for CYP2C9 genotyping
and to allow exploration of the effect of CYP2C9 polymorphism on the
pharmacokinetics (PK) of erdafitinib.
4.2, Exclusion Criteria, 
Criterion 6.1 
Exclusion criterion 6.1 was modified based on health authority
recommendation to remove baseline ocular conditions from exclusion
criteria. The rationale pertains to lack of predictive value of history of
macular/retinal medical history on the risk of occurrence of central serous
retinopathy (CSR)/retinal pigment epithelial detachment (RPED) based on
analysis of data from Phase 1 and 2 studies and evidence from the
available literature.
6.1.2.6, Guidelines for Eye 
Toxicity Associated With Vision 
Changes (Table 10) 
The following text was added under study drug management in Grade 1 to
3 of eye toxicity:
Retinal pigment epithelial detachment, if observed, should be
monitored at approximately 2-3-week intervals until resolution.

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Applicable Section(s) 
Description of Change(s)
Time and Events Schedule; 
9.8.6, Ophthalmologic Examination  
Tonometry was removed as an examination performed at screening, while
slit lamp biomicroscopy was added, expanding on the scope of eye
examination to be performed. The rationale pertains to a lack of value of
tonometry in assessing the ocular toxicities associated with erdafitinib.
Additionally, the wording “where available” was removed regarding
Optical Coherence Tomography (OCT), making OCT a comprehensive
part of the ophthalmological examination. Wording was added that a
follow-up ophthalmologic examination may be performed at regular
intervals as deemed necessary by the screening ophthalmologist.
For consistency, a note at the screening time point for the ophthalmologic
exam was added to read as such:
After 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.
8.3, Precautions for Concomitant 
Medications 
Added wording that the list of CYP3A4/2C9 inducers provided in
Attachment 5 and in http://medicine.iupui.edu/CLINPHARM/ddis/main-
table may not be exhaustive and up-to-date at any given time. The product
information of ongoing and new concomitant medications should be
consulted for the most accurate information on potential strong inducers of
CYP3A4 and CYP2C9.
4.1, Inclusion Criteria, Criterion 9.1 
and Criterion 11.2; 
16.2.3, Informed Consent 
Inclusion criterion 9.1 and informed consent section was modified to
clarify that when signing the informed consent form, the subject
understands the nature, significance, purpose of, procedures for, and
consequences of the study and is willing to participate in the study.
Inclusion criterion 11.2 was modified to add a definition for women of
childbearing potential:
Fertile, following menarche and until becoming post-menopausal
unless permanently sterile. Permanent sterilization methods include
hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
6.1.1, Dose Modifications and Dose 
Delays for Erdafitinib, Table 1 
Added wording to specify the action for Grade 2 toxicities:
None, or consider interruption if the toxicity is considered clinically
significant.
Revised the wording for Grade 2 toxicities for dose modification after
resolution of AE:
If interrupted, restart at the same dose if toxicity is completely
resolved to baseline or consider restarting at 1 dose lower if not
completely resolved to baseline (but resolved to Grade 1).
Revised the wording for Grade 3 toxicities for dose modification after
resolution of AE:
Restart at 1 dose lower if recovered to baseline (to Grade ≤1 or back
to baseline for non-hematologic toxicity) within 28 days; restart at 2
doses lower if not completely resolved to baseline (but resolved to
Grade 1) within 28 days.
6.1.2.7, Guidelines for the 
Management of Dry Eye 
Ocular demulcents were added as prophylactic management of dry eye.
Ocular demulcents replaced hydrating/lubricating eye gels and ointments
as reactive management of dry eye.

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Applicable Section(s) 
Description of Change(s)
10.2, Discontinuation of Study 
Treatment/Withdrawal From the 
Study  
Revised the wording for discontinuation of study treatment by the
investigator to read as:
 
The investigator believes that for safety reasons, tolerability reasons,
or impairment of the subject’s well-being (eg, due to AEs such as those
described in Section 6) it is in the best interest of the subject to
discontinue study treatment.
Added the following wording for discontinuation of study treatment by the
investigator:
 
The subject experiences an AE that, as described in Section 6, should
result in discontinuation of study drug.
Rationale: To remove time restrictions in subjects who undergo a new biopsy for fibroblast growth factor
receptor (FGFR) testing.
Time and Events Schedule; 
4, Subject Population 
Text updated to specify that, for subjects undergoing a new tissue biopsy
for molecular screening, the 30-day window will start with the first
planned study-related procedure other than the tissue biopsy.
Rationale: To expand the subject population eligible for cohort 1 and to align with current standard of care
following Food and Drug Administration (FDA) and European Medicines Agency (EMA) label restrictions of the
patient population eligible for treatment with anti-PD-(L)1 at frontline to those with high PD-L1 status and
common practice to administer a platinum-based treatment as standard of care as a second line treatment in this
patient population.
Synopsis; 2.1.1, Objectives; 
2.2, Hypothesis; 3.1, Overview of 
Study Design; 4.1, Inclusion 
Criteria, Criterion 5.1 
Revised inclusion criteria 5.1 to redefine subject population eligible for
cohort 1 and cohort 2 to read as such:
Cohort 1: Prior treatment with an anti-PD-(L)1 agent as monotherapy
or as combination therapy; no more than 2 prior lines of systemic
treatment.
Cohort 2: No prior treatment with an anti-PD-(L)1 agent; only 1 line
of prior systemic treatment.
Note: Subjects who received neoadjuvant or adjuvant chemotherapy
and showed disease progression within 12 months of the last dose are
considered to have received systemic therapy in the metastatic setting.
The study design and objectives were updated to indicate that efficacy of
erdafitinib versus chemotherapy or pembrolizumab in subjects with
advanced urothelial cancer harboring selected FGFR aberrations who have
progressed after 1 or 2 prior treatments, at least 1 of which includes an
anti-PD-(L)1 agent (cohort 1) or 1 prior treatment not containing an
anti-PD-(L)1 agent (cohort 2).
1.3, Immunotherapy 
Added text about pembrolizumab and atezolizumab as FDA and EMA-
approved medications for use in previously untreated subjects ineligible
for cisplatin-containing chemotherapy, adding that the indication in this
setting has been restricted to patients with high PD-L1 status and
considerations regarding the standard of care for patients who receive a
checkpoint inhibitor as frontline treatment.

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Applicable Section(s) 
Description of Change(s)
Rationale: To allow subjects with liver metastases and AST/ALT ≤5x institutional ULN to be included in the
study.
4.1, Inclusion Criteria, Criterion 8.2 Revised inclusion criterion 8.2 to allow subjects with liver metastases that
have alanine aminotransferase and aspartate aminotransferase that are ≤5x
the institutional upper limit of normal.
Rationale: To remove unnecessarily restrictive electrolyte result as inclusion criterion; no requirements for
normal potassium are present in the comparators’ labels and in the use of erdafitinib.
4.1, Inclusion Criteria, Criterion 8.2 Revised inclusion criterion 8.2 to remove requirement to have potassium
levels (electrolyte) within institutional normal limits.
Rationale: To allow subjects with low risk of progression from concurrent prostate cancer to enter the study.
4.2, Exclusion Criteria, 
Criterion 2.2 
Revised exclusion criterion 2.2 to allow subjects with localized prostate
cancer with a Gleason score of 3+4 that have been treated more than
6 months prior to the full study screening and are considered to have a
very low risk of recurrence.
Rationale: To remove grade definition for neuropathy and hearing loss and remove diabetes as an exclusion
criterion, as these are not contraindications to erdafitinib or comparator agents.
4.2, Exclusion Criteria, 
Criterion 10.1 
Revised exclusion criterion 10.1 to remove grade definitions for
neuropathy, and hearing loss.
4.2, Exclusion Criteria, 
Criterion 13.2 
Revised exclusion criterion 13.2 to remove poorly controlled diabetes
(hemoglobin A1c >8) as an example of a condition that could prevent,
limit, or cofound the protocol-specified assessments; instead, uncontrolled
ongoing medical conditions was added.
Rationale: To remove medications known to increase serum levels of phosphate (add as precautionary
medications) and medications known to increase the level ofcalcium as prohibited medications (no significant
effect of calcium metabolism is observed with erdafitinib).
8.2, Prohibited Medications; 
8.3, Precautions for Concomitant 
Medications
Medications known to increase serum levels of calcium were removed as
prohibited medications for subjects in Arms 1A and 2A for erdafitinib.
Medications known to increase serum levels of phosphate were removed
as prohibited medications and added to the section with precautions for
concomitantly administered medications.
Rationale: To update blood volumes collected at each phase of the study.
9.1.1, Overview  
The blood volume to be collected at screening was revised to 27 mL, the
blood volume to be collected over the course of the first 6 months was
updated to 266 mL, and the blood volume to be collected for every cycle
thereafter was updated to 22 mL.
Rationale: To allow subjects previously screened in the context of another study to by-pass the molecular
screening phase of this study.
9.1.2, Screening Phase 
The following text was added:
Subjects may by-pass the molecular screening phase of BLC3001 if
they have already been molecularly screened by the central laboratory
in the context of another Janssen-sponsored study.

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Applicable Section(s) 
Description of Change(s)
Rationale: To allow subject re-screening.
9.1.2, Screening Phase 
The following text was added:
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 internal quality control failure) to re-screen and
after consultation with the medical monitor.
Rationale: To clarify the requirement for monitoring of liver toxicity.
9.8.2, Clinical Laboratory Tests 
Added alkaline phosphatase test to the serum chemistry panel as it is
required for subjects on docetaxel and helpful in all subjects to evaluate
liver toxicity.
Rationale: Minor errors/prior omissions, editorial issues, or changes for clarity/consistency were noted and
corrected.
Time and Events Schedule; 
9.8.2, Clinical Laboratory Tests 
Clarified that serum phosphate and parathyroid hormone will be assessed
for all subjects at screening, and at all other time points for Arms 1A and
2A only. Clarified that thyroid stimulating hormone (TSH) and free
thyroxine 4 (FT4) will be assessed for all subjects at screening, and at all
other time points, beginning at Cycle 2, for Arm 2B only.
Time and Events Schedule 
Clarified that the urine or serum β-hCG pregnancy test will be assessed on
Day 1 of every cycle from Cycle 2 during the treatment phase.
4.2, Exclusion Criteria, 
Criterion 9.1 
Revised exclusion criterion 9.1 to exclude active infection with hepatitis B
or C (within the past 6 months). Wording was updated to read as such:
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)
4.2, Exclusion Criteria, 
Criterion 14.2 
Revised exclusion criterion 14.2 to clarify the most common cross-
hypersensitivities to docetaxel as polysorbate and paclitaxel.
6.1, Erdafitinib 
Up-titration guidelines were updated for subjects with serum phosphate
levels higher than 9.0 mg/dL to add that erdafitinib treatment will be
withheld until it returns to less than 7.0 mg/dL while initiating treatment
with a phosphate binder such as sevelamer.
6.1, Erdafitinib 
Added mmol/L values in brackets next to their corresponding serum
phosphate concentrations (represented in mg/mL) and included rounding
instructions.
6.1.2.1, Grading of 
Hyperphosphatemia and Nail 
Disorders (Table 3)
Added a ≥ symbol before the 2.9-3.2 mmol/L concentration under the
Grade 3 column.
6.1.2.6, Guidelines for Eye 
Toxicity Associated With Vision 
Changes (Table 10) 
For study management of Grade 2 toxicity, the following text was added:
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.
9.1.2, Screening Phase 
Added text that archival tumor tissue or a fresh biopsy sample will be sent
to the central laboratory to be analyzed with an investigational device.
9.4, Predictive and 
Pharmacodynamic Biomarkers 
Text has been updated to indicate that paired biopsies will be collected at
disease progression, not end of treatment.

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Applicable Section(s) 
Description of Change(s)
Time and Events Schedule; 
9.6, Actigraphy (Selected Sites) 
The text that subjects will be allocated in a 1:1 randomization was
removed. Text was revised that a target of a total of approximately 200
subjects will be recruited (100 subjects in each cohort).
Text regarding the Philips Actiwatch Spectrum actigraphy device was
revised to indicate that it will be worn for 1 to 2 weeks within the
screening period.
9.8.2, Clinical Laboratory Tests 
Clarified that serum phosphate, parathyroid hormone, TSH, and FT4 will
be tested for all subjects at screening.
9.8.5, Electrocardiogram  
Text added that at least 1 printout of all 3 ECGs should be produced and
stored in the subject’s source documents.
9.8.6, Ophthalmologic Examination  Clarified that the Amsler grid test will be administered by the treating
physician or nurse.
Added that OCT should be performed when fundoscopic retinal
abnormalities are observed, as well as each time ocular adverse events lead
to a subject being referred to an ophthalmologist.
The text recommending that color fundus photos or OCT images be
obtained and stored in the subject’s records for future reference was
removed and replaced with the following:
All images of the OCT scan must be stored in the subject’s records
and a redacted copy sent to the sponsor-selected central vendor for
possible future independent assessment.
9.8.8, Physical Examination  
Clarified that subjects should have a repeated physical examination at
Cycle 1 Day 1 prior to dosing if the previous one during screening
occurred more than 7 days before first dosing.
9.8.9, ECOG Performance Status 
Added that subjects should have a repeated ECOG assessment at Cycle 1
Day 1 prior to dosing if the previous one during screening occurred more
than 7 days before first dosing.
11.4, Pharmacokinetic and 
Pharmacokinetic/Pharmacodynamic 
Analyses 
The following text was removed:
Relationships between plasma concentrations or metrics of systemic
exposure and markers of pharmacological activities, efficacy or treatment-
emergent adverse events could also be explored as data allow using
population approaches (eg, non-linear mixed effects approaches).
12.3.3, Pregnancy  
Text was updated that follow-up information regarding the outcome of
pregnancy and any postnatal sequalae in the infant will be requested, not
required.
Attachment 6: Anticipated Events 
Hydronephrosis and oliguria were added to the list of anticipated events.
Throughout the protocol 
Anti-PD(L)1 was revised to read as anti-PD-(L)1.
Minor editorial, grammatical, spelling, or formatting changes were made.

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Amendment 2 (1 May 2018)
The overall reason for the amendment: The overall reason for the amendment is to address feedback from
health authorities.
Applicable Section(s) 
Description of Change(s)
Rationale: To clarify the timing of pregnancy test at screening and the frequency of pregnancy tests during
treatment until the end of systemic exposure.
Time and Events Schedule 
and 
9.7.4, Urine or Serum 
Beta-hCG Pregnancy Test
The protocol was revised to indicate that pregnancy test takes place 7 (not 14) days
or fewer before first dose administration. Pregnancy testing specified to take place
at the start of every 3-week cycle.
Rationale: Clarify the requirements for contraception in male subjects who are sexually active with women of
childbearing potential.
4.1, Inclusion Criteria, 
Criterion 11.1 
Revised inclusion criterion 11.1 for men who are sexually active with women of
childbearing potential: agrees to use a barrier method of contraception (eg, condom
with spermicidal foam/gel/film/cream/suppository)”
Rationale: To update wording to align with “Clinical Trial Facilitation Group” document for clarification of
effective contraception.
4.1, Inclusion Criteria, 
Criterion 11.1 
Added the following wording to 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
abstinence for the duration of exposure to study drug, and withdrawal are not
acceptable methods of contraception.)”
Rationale: To manage the risk of hypothyroidism associated with pembrolizumab.
Time and Events Schedule 
and 
9.8.2, Clinical Laboratory 
Tests
The protocol was revised to indicate that thyroid stimulating hormone and free
thyroxine 4 are tested at screening and then every other cycle during the study for
Arm 2B only.
Rationale: To align with contraindications associated with vinflunine.
4.1, Inclusion Criteria, 
Criterion 8.1 
Revised inclusion criterion 8.1 to indicate that the allowed platelet count for
subjects in Cohort 1 at sites choosing vinflunine chemotherapy is ≥100,000/mm3.
Rationale: Current wording indicates that subjects with Gilbert’s disease and any level of liver dysfunction are
eligible.
4.1, Inclusion Criteria, 
Criterion 8.1 
Revised inclusion criterion 8.1 to clarify acceptable levels of bilirubin: ≤1.5xULN
OR Direct bilirubin ≤ULN for subjects with total bilirubin levels >1.5xULN.
Rationale: To cover infection risk associated with docetaxel/vinflunine.
4.2.1, Exclusion Criteria 
for All Subjects, 
Criterion 13.1
Amended exclusion criterion 13.1 to “ongoing active infection requiring systemic
therapy.”
Rationale: To manage pulmonary toxicities associated with docetaxel.
4.2.2, Exclusion Criteria 
for Cohort 1 Subjects, 
Criterion 14.1
Added wording to indicate that for sites using docetaxel, subjects with evidence of
interstitial lung disease or active non-infectious pneumonitis are excluded.

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Applicable Section(s) 
Description of Change(s)
Rationale: To manage risk of cystoid macular edema associated with docetaxel.
6.2.2, Docetaxel 
Added the following wording for docetaxel as it relates to ocular toxicity: Cystoid
macular edema has been reported in subjects treated with docetaxel. Subjects with
impaired vision should undergo a prompt and complete ophthalmologic
examination. In case cystoid macular edema is diagnosed, docetaxel treatment
should be discontinued and appropriate treatment initiated.
Rationale: Recommendation from “Infectious Diseases Society of America Clinical Practice Guideline for
Vaccination of the Immunocompromised Host, Clinical Infectious Diseases.”
8.2, Prohibited 
Medications 
Added wording to indicate that live vaccines must be avoided for 3 months
following the last dose of study therapy.
Rationale: To align with vinflunine Summary of Product Characteristics.
8.2, Prohibited 
Medications 
Added wording that strong inducers of CYP3A4 should be avoided for subjects
receiving vinflunine.
Rationale: To manage risk of neurological toxicities associated with docetaxel and vinflunine.
Time and Events Schedule 
and
9.8.8, Physical
Examination
Indicated that a neurological examination is part of the physical examination.
Rationale: To align with results from clinical drug-drug interaction study.
8.3, Precautions for 
Concomitant Medications
Amended to include updated precautions for concomitant medications.
Attachment 5, Drugs 
Classified as Moderate to
Strong Inducers of
CYP3A4/2C9 Enzymes
Deleted tables containing strong inhibitors for CYP3A4/2C9 enzymes
Rationale: To address feedback from health authorities and to align with the requirements of the prescribing
information.
4.1, Inclusion Criteria, 
Criterion 11.1 
Revised the language for duration of breastfeeding restriction and for planning to
become pregnant, to clarify that it extends for the same duration of contraception
(during the study and for at least 6 months).
6.2.2.1, Docetaxel Dose 
Modifications, Table 12 
Correction of typos in Table 12, Docetaxel Dose Modifications for Drug-related
Adverse Events, Criteria for neutropenic fever and Neutropenia Grade 4 lasting
more than 7 days: (“platelet” mention corrected to “neutrophils”). Treatment
discontinuation option added to the second occurrence of neutropenic fever).
6.3, Pembrolizumab 
Wording to clarify evaluation and management of immune-related adverse
reactions was added.
6.3.1, Pembrolizumab 
Dose Modifications, Table 
13
Footnote added: pembrolizumab should be permanently discontinued for recurrent
Grade 3 adverse reactions.
Added a statement to reference prescribing information in the case of dose
modifications related to immune-related adverse reactions.

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Applicable Section(s) 
Description of Change(s)
Rationale: To address feedback from health authorities.
Time and Events Schedule 
Added collection of smoking history at screening.
Time and Events Schedule 
and 
9.8.2, Clinical Laboratory 
Tests
Added serum sodium, chloride, bicarbonate, and magnesium to the chemistry labs
scheduled during Cycle 1 Day 1 (baseline), Cycle 2 Day 1, and Cycle 3 Day 1 of
the study.
6.1.2.2, Guidelines for the 
Management of Elevated 
Phosphate Levels, Table 4 
Added clarification to the approach for dose reduction for persistent
hyperphosphatemia defined as serum phosphate ≥7 mg/dL for a period of 2 months
or serum phosphate ≥9 mg/dL for a period of 1 month and provided an example for
clinically necessary: in the presence of additional adverse events linked to
hyperphosphatemia or electrolyte disturbances.
Overview of Study Design, 
Dosage and 
Administration, 3.1,
Overview of Study Design,
Figure 1: Schematic
Overview of the Study, 6.3
Pembrolizumab Dose
modifications, 9.1.3,
Treatment Phase
Removed all occurrences of the statement: “Subjects in the pembrolizumab arm
will discontinue treatment at the completion of 2 years of pembrolizumab therapy.”
12.3.1, All Adverse Events 
Added wording to clarify that Japan will not identify anticipated events for the
health authorities.
Attachment 6, Anticipated 
Events
Added statement that some countries will not identify anticipated events.
12.3.2, Serious Adverse 
Events 
Added wording to clarify that progression of disease should not be considered an
adverse event.
17.9.2, Study Termination 
Possible reasons for study termination added: “in case of unacceptable risk,
intolerable toxicity, or change in the benefit/risk profile.”
6.2.1 Vinflunine 
A statement regarding conservation of sperm was added.
8.3, Precautions for 
Concomitant Medications 
The following wording was added: “…such as digoxin, dabigatran, and
fexofenadine (https://www.fda.gov/downloads/drugs/guidances/ucm292362.pdf);
in addition, drugs with a narrow therapeutic index should only be used where the
benefit outweighs the potential risk.”
11.2, Sample Size 
Determination
Added a statement that the average number of projected subjects per site is 2.3.
11.4 Pharmacokinetic and 
Pharmacokinetic/ 
Pharmacodynamic 
Analyses 
The following was added: “Relationships between plasma concentrations or
metrics of systemic exposure and markers of pharmacological activities, efficacy or
treatment-emergent adverse events may also be explored as data allow using
population approaches. Results of the analyses will be provided in a separate
report.”
Rationale: To align with pregnant partner informed consent form and allow appropriate safety follow-up for
babies born to subjects and partners of male subjects.
12.3.3, Pregnancy  
Added wording to allow for follow-up information to be collected up to 12 months
after the birth of a baby if a congenital anomaly or significant medical conditions is
diagnosed at birth.

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Applicable Section(s) 
Description of Change(s)
Rationale: To include information on an optional actigraphy sub-study.
Time and Events Schedule, 
2.1.1, Objectives, 
2.1.2 Endpoints,
9.6 Actigraphy (Selected
Sites), 9.6.1 Actigraphy-
derived Endpoints and
Analyses, 11.1 Subject
Information,
11.7 Actigraphy
Endpoints, 15 Study-
Specific Materials
Added information about actigraphy sub-study as well as corresponding objectives,
endpoints, study-specific materials, and evaluable population.
Rationale: To clarify exceptions for active malignancies.
4.2.1 Exclusion Criteria for 
all Subjects, Criterion 2.1 
Exceptions to the active malignancies exclusion criteria were added, which include
urothelial cancer, skin cancer treated within the last 24 months that is considered
completely cured, localized prostate cancer with a Gleason score of 6 (treated
within the last 24 months or untreated and under surveillance, and localized
prostate cancer with a Gleason score of 3+4 that has been treated more than 12
months prior to full study screening and considered completely cured.
Rationale: Clarification added to exclusion criterion 6.1.
4.2.1 Exclusion Criteria for 
All Subjects, Criterion 6.1 
The following exclusion wording was added: “or lens conditions, such as untreated
mature or hypermature senile cataract, affecting visual acuity that impair the ability
to interpret the Amsler grid test.”
Rationale: To clarify inclusion of metastatic or surgically unresectable urothelial cancer.
4.1 Inclusion Criteria, 
Criterion 3.1 
Updated inclusion criterion 3.1 to “Metastatic or surgically unresectable urothelial
cancer.”
Rationale: Minor errors were noted.
Throughout protocol 
Minor grammatical and formatting changes were made.
Amendment 1 (26 October 2017)
The overall reason for the amendment: The overall reason for the amendment is to clarify collection timepoints for
biomarker samples and correct numbering of exclusion criteria. Deleted text is shown in strikethrough and added text
in bold.
Applicable Section(s) 
Description of Change(s)
Rationale: Clarify collection timepoints for biomarker samples.
Time and Events 
Schedule 
For collection of tumor tissue for PD-L1 and biomarker testing, added Submit 1 archival
sample as soon as possible after enrollment. If submitting fresh biopsy, collect prior to
dosing on C1D1.
9.4, Predictive and 
Pharmacodynamic 
Biomarkers 
Optional paired biopsies will be collected pre-treatment (any time during the full screening
period prior to dosing on Cycle 1 Day 1), on-treatment (on or around Cycle 2 Day 1 on or
within 2 weeks after Cycle 2 Day 1), and at end of treatment (disease progression).

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Applicable Section(s) 
Description of Change(s)
Rationale: Correct formatting error.
4.2.2, Exclusion 
Criteria for Cohort 1
Subjects
Renumber exclusion criterion to 14
4.2.3, Exclusion 
Criteria for Cohort 2
Subjects
Renumber exclusion criterion to 15
Rationale: Clarify timing and outcome of erdafitinib up-titration.
3.2.3, Dosing 
Schedule for 
Erdafitinib 
In the first paragraph:
Treatment will be up-titrated to 9 mg, or maintained at 8 mg, or withheld, based on
phosphate level measured on Cycle 1 Day 14…
6.1, Erdafitinib 
In Up-titration Guidelines, Cycle 2 and 3 were deleted: On Day 14 of Cycles 1, 2, and 3, a
blood sample will be drawn to determine serum phosphate concentration…
Rationale: Minor errors were noted
Throughout protocol 
Minor grammatical and formatting changes were made.

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Status: Approved, Date: 20 January 2023
SYNOPSIS
A Phase 3 Study of Erdafitinib Compared with Vinflunine or Docetaxel or Pembrolizumab in Subjects with
Advanced Urothelial Cancer and Selected FGFR Gene Aberrations
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, including urothelial carcinoma.
OBJECTIVES, ENDPOINTS, AND HYPOTHESES
Primary Objective
The primary objective of this study is to evaluate efficacy of erdafitinib versus chemotherapy or
pembrolizumab in subjects with advanced urothelial cancer harboring selected FGFR aberrations who have
progressed after 1 or 2 prior treatments, at least 1 of which includes an anti-programmed death-
ligand 1(PD-[L]1) agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L)1 agent (cohort 2).
The primary endpoint of overall survival will be evaluated in 2 cohorts:
 
Cohort 1: erdafitinib versus chemotherapy (docetaxel or vinflunine) [subjects who have received prior
anti-PD-(L)1 agent]
 
Cohort 2: erdafitinib versus pembrolizumab [subjects who have not received prior anti-PD-(L)1 agent]
Secondary Objectives
 
To evaluate progression-free survival (PFS) of subjects treated with erdafitinib versus chemotherapy
or pembrolizumab
 
To evaluate the objective response rate (ORR) of subjects treated with erdafitinib versus chemotherapy
or pembrolizumab
 
To evaluate the health-related quality of life (HRQOL) of subjects treated with erdafitinib versus
chemotherapy or pembrolizumab
 
To evaluate the duration of response (DOR) for subjects treated with erdafitinib versus chemotherapy
or pembrolizumab
 
To characterize the safety profile of subjects treated with erdafitinib versus chemotherapy or
pembrolizumab
 
To evaluate the population pharmacokinetics of erdafitinib
Exploratory Objectives
 
To evaluate DNA, RNA, or protein biomarkers in tissue and blood samples which potentially predict
tumor response or resistance to erdafitinib, chemotherapy, or pembrolizumab
 
To assess the expression of immune markers (eg, PD-[L]1) and determine molecular subtype in tumor
samples
 
To evaluate changes in peripheral blood immune cell types, levels, and activation status in response to
erdafitinib, chemotherapy, or pembrolizumab
 
To assess changes in tumor immune cell infiltrate and gene expression related to bladder cancer
subtype, in response to erdafitinib in paired tumor biopsies
 
To evaluate the relationship between erdafitinib exposure and efficacy and safety endpoints

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To evaluate the relationship between CYP2C9 polymorphism and pharmacokinetics (PK) of
erdafitinib
Hypotheses
Cohort 1 hypothesis: Erdafitinib treatment prolongs overall survival (OS) in subjects with advanced
urothelial cancer harboring selected FGFR aberrations following 1 or 2 prior line(s) of systemic therapy,
with at least 1 line containing anti-PD-(L)1, compared with the OS of those treated with chemotherapy
(docetaxel or vinflunine).
Cohort 2 hypothesis: Erdafitinib treatment prolongs overall survival (OS) in subjects with advanced
urothelial cancer harboring selected FGFR aberrations following 1 prior line of systemic chemotherapy
without anti-PD-(L)1, compared with the OS of those treated with pembrolizumab.
OVERVIEW OF STUDY DESIGN
This is a randomized, open label, multicenter, global phase 3 study of erdafitinib versus standard of care,
consisting of chemotherapy (docetaxel or vinflunine) or anti-PD-(L)1 agent pembrolizumab, in subjects
with advanced urothelial cancer and selected FGFR aberrations who have progressed on or after 1 or 2 prior
treatments (cohort 1) or 1 prior treatment (cohort 2). Subjects will be assigned to Cohort 1 or Cohort 2
based upon prior treatment with an anti-PD-(L)1 agent. In Cohort 1, subjects who have received prior anti-
PD-(L)1 will be randomized to erdafitinib versus chemotherapy (approximately 280 subjects). In Cohort 2,
subjects who have not received prior anti-PD-(L)1 will be randomized to erdafitinib versus pembrolizumab
(approximately 350 subjects). Cohort 1 and Cohort 2 will be assessed independently.
For each cohort, a review of the safety data will be performed by an Independent Data Monitoring
Committee (IDMC) after at least 60 subjects have been enrolled in that cohort and every 6 months
afterwards. The IDMC will also review efficacy and safety data for the predefined interim analysis.
The Screening Phase will start with molecular screening, which will be performed by a central laboratory
or by review of local historical test results submitted to the sponsor for molecular eligibility assessment.
Full study screening 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 extend from
randomization until disease progression, intolerable toxicity, withdrawal of consent or decision by the
investigator to discontinue treatment. 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 for the respective cohort), whichever comes first.
Study completion and end of study are distinct timepoints. Study completion occurs at the end-of-data-
collection timepoint for both cohorts, which is defined as when the clinical cutoff for the final analysis has
been achieved.  End of study is the time the last subject receives the last dose of study drug on the study.
The LTE Phase begins with the approval of Amendment 6 and with achievement of the clinical cut-off for
the final analysis for each cohort. 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.
SUBJECT POPULATION
Subjects will be adults with histologic demonstration of Stage IV transitional cell carcinoma of the
urothelium and documentation of disease progression. Subjects will have received 1 or 2 prior line(s) of
systemic treatment (cohort 1) and 1 prior line of systemic treatment (cohort 2) for metastatic urothelial
cancer and meet appropriate molecular eligibility criteria. ECOG performance status must be 0, 1, or 2, and
bone marrow, liver, and renal function must be within protocol-specified limits.

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DOSAGE AND ADMINISTRATION
Erdafitinib will be provided as tablets for oral administration. Subjects randomized to erdafitinib will be
instructed to take erdafitinib orally, at a starting dose of 8 mg, once daily for 21 days on a 21-day cycle
until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to
discontinue treatment. Each dose should be taken at approximately the same time each day, with or without
food. Dose adjustments will be made based on Cycle 1 Day 14 serum phosphate levels.
Subjects randomized to chemotherapy will receive vinflunine 320 mg/m2 as a 20-minute intravenous
infusion once every 3 weeks or docetaxel 75 mg/m2 as a 1-hour intravenous infusion every 3 weeks.
Treatment with either agent will be administered until disease progression, intolerable toxicity, withdrawal
of consent or decision by the investigator to discontinue treatment. The choice of which chemotherapy
regimen to use at each site will be determined by the investigator. Subjects randomized to immunotherapy
will receive pembrolizumab 200 mg as a 30-minute intravenous infusion once every 3 weeks, until disease
progression, intolerable toxicity, withdrawal of consent, or decision by the investigator to discontinue
treatment.
EVALUATIONS
Assessment of responses for solid tumors will be performed according to RECIST (version 1.1) by
investigators. Venous blood samples will be collected for determination of plasma concentrations of
erdafitinib and alpha-1-acid glycoproteins, total protein, and fraction unbound, if required, at the time points
specified in the Time and Events Schedule, for all subjects randomized to erdafitinib arms (Arm 1A and
Arm 2A). Tissue collected on study will be used to assess the immune marker status and identify the
molecular subtype of patient tumors. Germline DNA will be collected for subjects on erdafitinib for
CYP2C9 genotyping. Patients’ health-related quality of life symptoms, functioning, and general well-being
will be captured using 3 PRO measures: the FACT-Bl, PGIS, and the EQ-5D-5L. Safety assessments will
be based on medical review of adverse event (AE) reports and the results of vital sign measurements,
electrocardiograms, physical examinations, clinical laboratory tests, ECOG performance status,
ophthalmologic examinations, and other safety evaluations at specified time points as described in the Time
and Events Schedule.
STATISTICAL METHODS
The primary endpoint is OS. The primary efficacy analysis will be based on the intent-to-treat (ITT)
population that includes all randomized subjects in each cohort.  The Kaplan-Meier method will be used to
estimate the distribution of OS for each treatment group within each cohort. The stratified log-rank test,
with region (North America vs. European Union [EU] vs. rest of world), Eastern Cooperative Oncology
Group (ECOG) performance status (0 or 1 vs. 2), and disease distribution (presence vs. absence of visceral
metastases in lung, liver, or bone) as stratification factors, will be used to compare survival curves of OS
between the 2 treatment arms in each cohort. There is one planned interim analysis for each cohort.

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Parameter
NOTES 
Screening Phase 
Treatment Phasea (21-day cycles)
Follow-Up
Phasea
Molecular 
Eligibility 
Full Study 
Screening 
Cycles 1, 2, 3 
Cycle 4+ 
End of
Treatment
Day 1 
Day 14  Day 1 
Visit Window  
N/A 
-30 
days 
-14 
days 
C1: 0 days 
C2, C3: -2 
to +2 days 
-2 to +2 
days 
-2 to +2 
days 
30 (+7) days 
after last 
dose
every 12
weeks±7 days
stabilizes, or is deemed irreversible, subject dies, or subsequent
therapy is started, whichever occurs first.
Survival status and 
subsequent anticancer 
therapy 
May be assessed via telephone call. Survival status and start of
alternate anticancer therapy will be monitored until death,
withdrawal of consent, or study completion (ie,the end of data 
collection timepoint has been achieved for the respective cohort
(See Section 17.9.1), whichever occurs first
X
Abbreviations to Time and Events Schedule: AE=adverse event; C=cycle; CT= computed tomography; ctDNA=circulating tumor DNA; D=day; ECG=electrocardiogram; ECOG=Eastern Cooperative Oncology
Group; FGFR=fibroblast growth factor receptor; FT4=free thyroxine 4; hr=hour; ICF=informed consent form; MRI= magnetic resonance imaging; PBMC=peripheral blood mononuclear cell; PK=pharmacokinetic;
PRO=patient reported outcome; TCR=T cell receptor; TSH=thyroid stimulating hormone
* 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.
For subjects signing a new full-study ICF for the purpose of undergoing a new tissue biopsy for molecular screening, the 30-day window starts with the first planned study-related procedure other than the
tissue biopsy; however, AEs will need to be collected from the time of full-study ICF sign off.
**After 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.
a. 
Guidance for study conduct for ongoing subjects in the event of a national disaster is provided in Attachment 7.
b. 
The LTE Phase begins with the approval of Amendment 6 and with achievement of the clinical cut-off for the final analysis for each cohort. (For Cohort 1, the Sponsor will notify the investigators if the
interim analysis will be considered the final analysis.) Upon initiation of the LTE Phase, data collection will conclude. Subjects in the respective cohort 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. As an alternative to entering the LTE Phase, subjects may exit the study and continue to
receive treatment on any other post-trial access program, when permitted by local regulations. During this period (when study drug will be supplied on this study by the Sponsor after the end of data
collection timepoint), only serious adverse events will be reported to the Company safety repository.

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ABBREVIATIONS
ADL 
activities of daily living
AE 
adverse event
α1-AGP  
α1-acid glycoprotein
AUC  
area under the curve
AUCu  
area under the curve for unbound drug
BID  
bis in die (two times each day)
BSC 
best supportive care
CLIA  
Clinical Laboratory Improvement Amendments
Cmax  
maximal concentration
CR  
complete response
CRF  
case report form
CrCl 
creatinine clearance
CSR  
central serous retinopathy
CT  
computed tomography
ctDNA  
circulating tumor DNA
CYP  
cytochrome P450
DNA  
deoxyribonucleic acid
DOR  
duration of response
ECG  
electrocardiogram
ECOG  
Eastern Cooperative Oncology Group
eCRF  
electronic case report form
eDC  
electronic data capture
EMA  
European Medicines Agency
EQ-5D-5L 
European Quality of Life –5 Dimensions-5 Levels
EU  
European Union
FACT-Bl 
Functional Assessment of Cancer Therapy –Bladder Cancer
FDA  
Food and Drug Administration
FGFR  
fibroblast growth factor receptor
FT4 
free thyroxine 4
GCP  
Good Clinical Practice
HR  
hazard ratio
HRQOL 
health-related quality of life
ICF  
informed consent form
ICH  
International Council for Harmonisation
IDMC  
Independent Data Monitoring Committee
IEC  
Independent Ethics Committee
IHC  
immunohistochemistry
IRB  
Institutional Review Board
ITT  
intent-to-treat
IWRS  
interactive web response system
LTE 
Long-term Extension [Phase]
MedDRA  
Medical Dictionary for Regulatory Activities
MRI 
magnetic resonance imaging
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events
NGS  
next-generation sequencing
NK  
natural killer
NSCLC  
non-small cell lung cancer
OCT  
optical coherence tomography
ORR  
objective response rate
OS  
overall survival
PBMC  
peripheral blood mononuclear cell
PD 
pharmacodynamic(s)
PD-(L)1 
programmed death-ligand 1
PFS  
progression-free survival
P-gp 
P-glycoprotein

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PK 
pharmacokinetic(s)
PQC  
Product Quality Complaint
PR 
partial response
PRO  
Patient-Reported Outcome
PGIS  
Patient-Global Impression of Severity
QID  
quater in die (four times each day)
RECIST 
Response Evaluation Criteria in Solid Tumors
RGQ  
Rotor-Gene Q
RNA  
ribonucleic acid
RPED  
retinal pigment epithelial detachment
RT-PCR  
reverse transcription polymerase chain reaction
SMT  
Safety Management Team
SUSAR  
suspected unexpected serious adverse reaction
USP  
United States Pharmacopeia
TCGA  
The Cancer Genome Atlas
TCR  
T-cell receptor
TID  
three times a day
TSH  
thyroid stimulating hormone
ULN  
upper limit of normal
US  
United States

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1. 
INTRODUCTION
Erdafitinib (JNJ-42756493) is a selective and potent pan fibroblast growth factor receptor (FGFR)
inhibitor with demonstrated clinical activity in subjects with solid tumors identified to have
alterations in the FGFR pathway, including urothelial carcinoma.
This Phase 3 study will evaluate single-agent erdafitinib versus established chemotherapy agents
(docetaxel and vinflunine) and an anti-programmed death-ligand 1 (PD-[L]1) agent
(pembrolizumab) in relapsed/refractory subjects with selected FGFR gene aberrations
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.
1.1. 
Bladder Cancer
The worldwide age-standardized incidence rate of bladder cancer (per 100,000 person/years) is
9.0 for men and 2.2 for women (Ferlay 2013). Worldwide, the bladder cancer age-standardized
mortality rate (per 100,000 person/years) was 3.2 for men versus 0.9 for women in 2012 (Ferlay
2013). Bladder cancer incidence and mortality rates vary across countries due to differences in risk
factors, detection and diagnostic practices, and availability of treatments.
Half of the patients with muscle-invasive urothelial cancer relapse after radical cystectomy,
depending on the pathological stage of the primary tumor and the nodal status. Local recurrence
accounts for 30% of relapses, whereas distant metastases are more common. Ten to 15 percent of
patients are already metastatic at diagnosis. Prognostic factors are crucial for assessing results and
stratifying phase 3 studies. In a multivariate analysis, Karnofsky performance status of <80% and
presence of visceral metastases are independent predictors of poor survival (Bajorin 1999).
1.2. 
Second-line Chemotherapy
Results of second-line treatment with chemotherapy from phase 2 studies are highly variable and
depend on patient selection (Bellmunt 2014). Several agents have been tested in this setting as
monotherapy or in combination (Yafi 2011). Response rates with monotherapy are lower than with
combinations, but progression-free survival (PFS) has been short with both options. The only valid
randomized phase 3 study in this patient population tested vinflunine and best supportive care
(BSC) versus BSC alone (Bellmunt 2014).Based on the available evidence, taxanes and vinflunine
are commonly recommended chemotherapy agents (NCCN 2017).
1.2.1. 
Docetaxel
Docetaxel, an analog of paclitaxel, is a taxane chemotherapeutic agent that received initial
approval in the United States (US) in 1996 for the treatment of patients with advanced breast cancer
who had failed front-line chemotherapy, and subsequently in a number of other malignancies.
Docetaxel is not licensed for the treatment of patients with urothelial cancer, however it is
commonly used in this setting based on the results of a phase 2 study conducted in patients (n 30)
with advanced urothelial cancer who had failed 1 prior line of cisplatin-based treatment. Docetaxel
was active as a single agent when administered at a dose of 100 mg/m2 as a 1-hour infusion every
3 weeks (McCaffrey 1997). Four patients (13.3%) had a partial response (PR), with a duration of

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response (DOR) from 3 to 8 months. Estimated median overall survival (OS) for all patients was
9 months. Myelosuppression was the major toxicity, with neutropenia, anemia, and
thrombocytopenia frequently reported. Clinically significant nonhematologic toxicity was low.
For further information regarding docetaxel, refer to the locally available prescribing information
for docetaxel.
1.2.2. 
Vinflunine
Vinflunine, a third-generation vinca alkaloid, provided promising results in phase 2 studies. A
randomized Phase 3 study compared vinflunine plus BSC against BSC alone in patients
progressing after first-line treatment with platinum-containing combination chemotherapy for
metastatic urothelial carcinoma (Bellmunt 2009). The results showed an objective response rate
(ORR) of 8.6%, a clinical benefit with a favorable safety profile and, most importantly, a survival
benefit in favor of vinflunine, which was statistically significant in the eligible patient population
(not in the intent-to-treat [ITT] population). Currently, vinflunine is the only approved second-line
chemotherapy treatment and is approved in the EU.
For further information regarding vinflunine, refer to the locally available prescribing information.
1.3. 
Immunotherapy
Bacillus Calmette-Gue ́rin (BCG) was approved by the US Food and Drug Administration (FDA)
in 1990 as an immunotherapy agent for non-muscle invasive urothelial carcinoma. The
effectiveness of BCG was an early sign that urothelial carcinoma is an immune-responsive tumor
(Davarpanah 2017). More recently, checkpoint inhibitors are also promising in the treatment of
urothelial carcinoma (Miller 2017). Atezolizumab (Tecentriq®), an anti-PD-(L)1 monoclonal
antibody, received accelerated approval for the treatment of patients with locally advanced or
metastatic urothelial carcinoma whose disease has progressed during or after platinum-based
chemotherapy orwithin 12 months of having received platinum-containing chemotherapy. In rapid
succession, nivolumab (Opdivo,® anti-PD-(L)1 monoclonal antibody), durvalumab (Imfinzi,®
anti-PD-(L)1 monoclonal antibody), and avelumab (Bavencio,® anti-PD-(L)1 monoclonal
antibody) were all granted accelerated approval in the second-line setting. In Phase 2 or Phase 1b
trials, overall response rates have ranged from 13.1% to 19.6%. Most recently, in May 2017,
pembrolizumab (Keytruda,® anti-PD-(L)1 monoclonal antibody) was approved by the FDA for
second-line treatment of locally advanced or metastatic urothelial carcinoma based on a phase 3
study. Pembrolizumab and atezolizumab also have been approved by the FDA and EMA for use
in previously untreated patients ineligible for cisplatin-containing chemotherapy; however, the
indication in this setting has subsequently been restricted to those patients whose tumor expresses
PD-(L)1 with a Combined Positive Score ≥10 (pembrolizumab) or PD-(L)1 stained tumor-
infiltrating immune cells covering ≥5% of the tumor area (atezolizumab). The restriction has
reduced the previously untreated population eligible for treatment with a checkpoint inhibitor. For
those patients who still receive single agent pembrolizumab or atezolizumab as frontline treatment,
common clinical practice in second line is to administer platinum-based treatment as standard of
care.

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1.3.1. 
Pembrolizumab
In a multicenter, randomized, active-controlled Phase 3 study (KEYNOTE-045), patients with
locally advanced or metastatic urothelial carcinoma and disease progression on or after platinum-
containing chemotherapy were randomly assigned (1:1) to receive either pembrolizumab 200 mg
every 3 weeks (n 270) or investigator’s choice of a chemotherapy regimen (paclitaxel [n 84],
docetaxel [n 84], or vinflunine [n 87]) every 3 weeks (n 255). Patients without disease
progression could be treated with pembrolizumab up to 24 months. The median duration of
exposure was 3.5 months for pembrolizumab and 1.5 months for chemotherapy. Objective
response rate (ORR) was 21% for pembrolizumab and 11% for chemotherapy (p 0.002). Median
overall survival (OS) was 10.3 months for the pembrolizumab group and 7.4 months for the
chemotherapy group (HR 0.73; 95% CI: 0.59, 0.91, p 0.004). The study demonstrated statistically
significant improvements in OS and ORR for patients assigned to pembrolizumab compared with
chemotherapy. No statistically significant difference in progression-free survival (PFS) between
the 2 treatment arms was observed. The most common adverse reactions (≥20%) included fatigue,
pruritus, diarrhea, decreased appetite, rash, pyrexia, cough, dyspnea, musculoskeletal pain,
constipation, and nausea.
For further information regarding pembrolizumab, refer to the locally available prescribing
information for pembrolizumab.
1.4. 
Fibroblast Growth Factor Receptors and Erdafitinib
1.4.1. 
Fibroblast Growth Factor Receptors
Overexpression of fibroblast growth factor receptors (FGFRs), or aberrant regulation of their
activity, has been implicated in many forms of human malignancies including urothelial
carcinoma.
Fibroblast growth factor receptors are protein tyrosine kinases and consist of 4 members (FGFR1
to FGFR4). Upon binding to their natural ligand, FGF family members, FGFRs dimerize and
autophosphorylate the tyrosine residue in the kinase domain activation loop to become fully
activated. Activated FGFR further phosphorylate multiple signaling proteins bound to their
intracellular portion, resulting in activation of Ras/mitogen-activated protein kinase (MAPK) and
PI3-kinase/Akt signaling pathways. Other downstream signaling components of FGFRs include
Src, and Rsk. The result is FGFR stimulation of cell growth, survival, migration, and
differentiation depending on the cell type.
Fibroblast growth factor receptors are present in many types of normal and tumor cells and have
been shown to play an important role in tumor cell growth, survival, and migration as well as in
maintaining tumor angiogenesis. Overexpression of FGFRs, or aberrant regulation of their activity,
has been implicated in many forms of human malignancies. Fibroblast growth factor receptor
activating mutation, gene amplification, and translocation have been associated with neoplastic
progression and tumor vascularization in multiple cancer types, including breast, lung, prostate,
endometrial, gastric, and urothelial carcinoma. Therefore, targeting FGFRs in urothelial cancer

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with a small molecule kinase inhibitor is an attractive strategy for the development of a novel
cancer treatment.
1.4.2. 
Erdafitinib
Erdafitinib is an oral pan-FGFR tyrosine kinase inhibitor with IC-50 values in the low nanomolar
range for all members of the FGFR family (FGFR1 to 4). It has demonstrated potent inhibition of
cell proliferation with IC-50 values ranging from <1 to <1000 nM in FGFR pathway-activated
cancer cell lines. Erdafitinib has been shown to have in vivo antitumor activity in mouse xenograft
models of FGFR-driven gastric, bladder, and squamous 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 dose-related increase in Cmax and AUC and time-independent PK
within the dose range of 0.5 mg to 12 mg, both after single and multiple daily dosing. Median tmax
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 CYP450 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 recently completed 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, 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%). Thirteen
subjects (7%) discontinued treatment due to AEs.
A global phase 2 study (Study 42756493BLC2001) is ongoing in subjects with relapsed/refractory
advanced urothelial cancer with selected FGFR mutations and translocations. As of 09 June 2017,
173 subjects have been treated in this study; 33 subjects in the 10 mg intermittent dosing regimen,
78 subjects in the 6 mg daily regimen, and 62 subjects in the 8mg daily regimen. The ORR,
including confirmed and unconfirmed complete response (CR) and partial response (PR), was
39.7% in the 8 mg once daily regimen. For subjects in the 8 mg once daily group whose dose was
increased to 9 mg, ORR was 50.0%. The most frequently reported AEs, most of which were
Grade 1 or 2 in severity, were hyperphosphatemia (54.3%), diarrhea (49.7%), dry mouth (42.8%),
stomatitis (42.2%) and decreased appetite (33.5%). Fourteen subjects (8%) discontinued treatment
due to AEs.

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For the most comprehensive nonclinical and clinical information regarding erdafitinib, refer to the
latest version of the Investigator's Brochure (IB).
1.5. 
Overall Rationale for the Study
Metastatic bladder cancer carries a dismal prognosis, with 5-year survival rate of only 5.0%
(Howlader 2016). The mainstay of treatment is still limited to platinum-based chemotherapy in
frontline, leading to a disappointing median OS of approximately 15 months. Second-line
treatment with single-agent chemotherapy has a response rate of approximately 8% to 10% and
OS of approximately 6 to 8months. More recently, outcomes with compounds targeting the
PD-1/PD-(L)1 pathway were reported in patients with disease progression on or after 1 prior line
of treatment, with ORR of 15% to 20% and median overall survival of approximately 8 to 10
months. In randomized phase 3 studies, conflicting results were observed with pembrolizumab
demonstrating significant improvement in overall survival against standard of care chemotherapy
and atezolizumab failing to demonstrate an improvement in the same setting. Despite the recent
improvement in outcomes provided by compounds targeting the PD-1/PD-(L)1 pathway, all
current treatment options still have relatively limited clinical activity as second-line therapy; and
at the time of initial protocol development, no targeted therapy was approved for treating specific
subsets of urothelial cancer subjects with FGFR alterations.
The clinical data from phase 1 and 2 clinical studies demonstrate erdafitinib is active as a
monotherapy in subjects with relapsed/refractory metastatic urothelial cancer with selected FGFR
translocations and mutations.
Therefore, this phase 3 study aims to demonstrate superiority of single agent erdafitinib over
established (chemotherapy) and emerging (anti PD-1/PD-[L]1 monoclonal antibodies) standard of
care options in relapsed/refractory subjects with selected FGFR gene aberrations.
2. 
OBJECTIVE, ENDPOINTS, AND HYPOTHESES
2.1. 
Objectives and Endpoints
2.1.1. 
Objectives
Primary Objective
The primary objective of this study is to evaluate efficacy of erdafitinib versus chemotherapy or
pembrolizumab in subjects with advanced urothelial cancer harboring selected FGFR aberrations
who have progressed after 1 or 2 prior treatments, at least 1 of which includes an anti-PD-(L)1
agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L)1 agent (cohort 2).
The primary endpoint of OS will be evaluated in 2 cohorts:
 
Cohort 1: erdafitinib versus chemotherapy (docetaxel or vinflunine) [subjects who have
received prior anti-PD-(L)1 agent]
 
Cohort 2: erdafitinib versus pembrolizumab [subjects who have not received prior
anti-PD-(L)1 agent]

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Secondary Objectives
 
To evaluate progression-free survival (PFS) of subjects treated with erdafitinib versus
chemotherapy or pembrolizumab
 
To evaluate the objective response rate (ORR) of subjects treated with erdafitinib versus
chemotherapy or pembrolizumab
 
To evaluate the health-related quality of life (HRQOL) of subjects treated with erdafitinib
versus chemotherapy or pembrolizumab
 
To evaluate the duration of response (DOR) for subjects treated with erdafitinib versus
chemotherapy or pembrolizumab
 
To characterize the safety profile of subjects treated with erdafitinib versus chemotherapy or
pembrolizumab
 
To evaluate the population PK of erdafitinib
Exploratory Objectives
 
To evaluate DNA, RNA, or protein biomarkers in tissue and blood samples which potentially
predict tumor response or resistance to erdafitinib, chemotherapy, or pembrolizumab
 
To assess the expression of immune markers (eg, PD-[L]1) and determine molecular subtype
in tumor samples
 
To evaluate changes in peripheral blood immune cell types, levels, and activation status in
response to erdafitinib, chemotherapy, or pembrolizumab
 
To assess changes in tumor immune cell infiltrate and gene expression related to bladder
cancer subtype, in response to erdafitinib in paired tumor biopsies
 
To evaluate the relationship between erdafitinib exposure and efficacy and safety endpoints
 
To evaluate the relationship between CYP2C9 polymorphism and PK of erdafitinib
2.1.2. 
Endpoints
Primary Endpoint
The primary endpoint is overall survival (OS). Overall survival is measured from the date of
randomization to the date of the subject’s death. If the subject is alive or the vital status is unknown,
the subject will be censored at the date the subject was last known to be alive.
Secondary Endpoints
 
PFS: duration in days from the date of randomization to the date of disease progression
(assessed per RECIST v1.1 by the investigator) or relapse from CR or death, whichever is
reported first. For subjects who do not have disease progression and are alive, as well as for
subjects with unknown disease progression or unknown survival status as of the clinical cutoff
date, PFS will be censored at the date of the last adequate disease assessment. If there is no
postbaseline tumor assessment for a subject, PFS will be censored on the date of
randomization. Refer to the Statistical Analysis Plan (SAP) for further details regarding

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censoring rules. Adequate disease assessment is defined as having sufficient evidence to
indicate correctly that progression has or has not occurred.
 
ORR: the proportion of subjects who achieve complete response or partial response, as
assessed per RECIST v1.1 by the investigator.
 
Change from baseline in patient-reported health status and physical functioning scales of the
Functional Assessment of Cancer Therapy 
 Bladder Cancer (FACT-Bl), Time Until
Symptom Deterioration (subset of FACT-Bl items), Patient-Global Impression of Severity
(PGIS), and utility and visual analog scale of the European Quality of Life-5 Dimensions-5
Levels Questionnaire (EQ-5D-5L).
 
DOR: for responders, duration in days 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. The censoring is similar to PFS.
 
Safety: collection of adverse event, clinical laboratory values, electrocardiograms, vital signs,
ophthalmologic evaluations, physical examinations.
 
Oral clearance, area under the plasma concentration-time curve (and other parameters, as
needed and as data permits) will be estimated using a population approach.
Exploratory Endpoint(s)
 
PD-(L)1 expression level by immunohistochemistry (IHC), and bladder cancer subtype by
RNA sequencing or other method(s) as appropriate
 
Profile and activation status of peripheral immune cell subtypes by flow cytometry, T cell
receptor (TCR) sequencing, or alternate method(s) as appropriate
 
Tumor T cell infiltrate in paired biopsies by immunohistochemistry, and gene expression
related to bladder cancer subtype by RNA sequencing or alternate method(s) as appropriate
 
Use of models, such as Emax, to evaluate parameters describing the effect of erdafitinib
exposure on clinical endpoints; for instance, erdafitinib concentration or metrics of exposure
leading to 50% of the maximal effect
 
Effect of CYP2C9 polymorphism on the PK of erdafitinib
Refer to Section 9 for evaluations related to endpoints.
2.2. 
Hypothesis
Cohort 1 hypothesis: Erdafitinib treatment prolongs overall survival (OS) in subjects with
advanced urothelial cancer harboring selected FGFR aberrations following 1 or 2 prior line(s) of
systemic therapy, with at least 1 line containing anti-PD-(L)1, compared with the OS of those
treated with chemotherapy (docetaxel or vinflunine).
Cohort 2 hypothesis: Erdafitinib treatment prolongs overall survival (OS) in subjects with
advanced urothelial cancer harboring selected FGFR aberrations following 1 prior line of systemic
chemotherapy without anti-PD-(L)1, compared with the OS of those treated with pembrolizumab.

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3. 
STUDY DESIGN AND RATIONALE
3.1. 
Overview of Study Design
This is a randomized, open-label, multicenter, global phase 3 study of erdafitinib versus standard
of care, consisting of chemotherapy (docetaxel or vinflunine) or anti-PD-(L)1 agent
pembrolizumab, in subjects with advanced urothelial cancer and selected FGFR aberrations who
have progressed on or after 1 or 2 prior treatments (cohort 1) or 1 prior treatment (cohort 2).
Subjects will be assigned to Cohort 1 or Cohort 2 based upon prior treatment with an anti-PD-(L)1
agent. In Cohort 1, subjects who have received prior anti-PD-(L)1 will be randomized to erdafitinib
versus chemotherapy (approximately 280 subjects). In Cohort 2, subjects who have not received
prior anti-PD-(L)1 will be randomized to erdafitinib versus pembrolizumab (approximately 350
subjects). Cohort 1 and Cohort 2 will be assessed independently.
An Independent Data Monitoring Committee (IDMC) will be commissioned for this study. Refer
to Section 11.9 for details.
For each cohort, a review of the safety data will be performed by an IDMC after at least 60 subjects
have been enrolled in that cohort and every 6 months afterwards. A review of one predefined
interim analysis for each cohort will also be performed by the IDMC on both safety and efficacy
data. Details are provided in Section 11.9.
The Screening Phase will start with molecular screening, which will be performed by a central
laboratory or by review of local historical test results submitted to the sponsor for molecular
eligibility assessment (see details in Section 9.1.2). Full study screening 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 extend from randomization until disease
progression, intolerable toxicity, withdrawal of consent or decision by the investigator to
discontinue treatment. 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 (ie,
the end of data collection timepoint has been achieved for the respective cohort discussed in
Section 17.9.1), whichever comes first. Continued treatment with study drug after the end of data
collection timepoint is discussed in Section 6.4.
A diagram of the study design is provided in Figure 1.

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Figure 1: 
Schematic Overview of the Study
Note: The Long-term Extension Phase is not included in the schematic (see Attachment 8).
Treatment until disease progression, intolerable toxicity, withdrawal of consent, or decision by investigator.
Subjects who meet all eligibility requirements will be entered into the study. Randomization to
treatment will be within each cohort. In Cohort 1, subjects must have progressed on or after 1 or 2
prior line(s) of systemic treatment, with at least 1 line including anti-PD-(L)1 as monotherapy or
as combination therapy, will be randomized 1:1 to erdafitinib (Arm 1A) or chemotherapy
(vinflunine or docetaxel, Arm 1B). In Cohort 2, subjects must have progressed after one prior line
of systemic treatment not containing anti-PD-(L)1 and will be randomized 1:1 to erdafitinib (Arm
2A) or pembrolizumab (Arm 2B). Stratified randomization will be implemented within each cohort
with the following factors: region (North America vs European Union [EU] vs Rest of World),
Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1 vs 2), and disease
distribution (presence vs absence of visceral [lung, liver, or bone] metastases).
Subjects will be assessed for disease response by the investigator according to Response
Evaluation Criteria in Solid Tumors (RECIST; v1.1) guidelines. Treatment with erdafitinib and
pembrolizumab may continue beyond the initial demonstration of disease progression, according
to criteria in Section 9.2.2.
The LTE Phase begins with the approval of Amendment 6 and with achievement of the clinical
cut-off for the final analysis for each cohort. (For Cohort 1, the Sponsor will notify the investigators
if the interim analysis will be considered the final analysis.) Upon initiation of the LTE Phase, the

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follow up of subjects will end and study data collection will conclude in the clinical database.
During this LTE Phase (when study drug will be supplied by the Sponsor after the data collection
timepoint), only serious adverse events will be reported to the Company safety repository. Subjects
in the respective cohort 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 (Section
6.4). As an alternative to entering the LTE Phase, subjects may exit the study and continue to
receive treatment on any other post-trial access program, when permitted by local regulations. In
the event of a decision by the Sponsor to allow cross-over to erdafitinib following the final analysis
for each respective cohort, investigators will be notified. Detail regarding the LTE Phase is
provided (including a Time and Events Schedule) in Attachment 8.
3.2. 
Study Design Rationale
3.2.1. 
Choice of Comparators
While platinum-based combination chemotherapy leads to high response rates in patients with
advanced urothelial cancer of the bladder in the front-line setting, most patients will ultimately
progress and optimal treatment in the second-line setting still needs to be determined. Factors such
as advanced age and frailty, poor performance status, comorbidities, and rapidly progressive
disease have rendered assessment of treatment options difficult.
There are no approved second-line chemotherapies for metastatic urothelial cancer in the US,
while vinflunine is approved in the EU for the treatment of advanced or metastatic transitional cell
carcinoma of the urothelial tract after failure of a prior platinum-containing regimen. Vinflunine
has demonstrated survival benefit compared with BSC in a randomized phase 3 setting, but it has
not been compared with other currently used agents such as taxanes.
National Comprehensive Cancer Care guidelines acknowledge that data on second-line systemic
therapy for locally advanced or metastatic disease is highly variable, and that docetaxel is one of
the available options (NCCN 2017). Although no labeled dosing guidelines are available for
urothelial cancer, docetaxel is commonly administered at 75 mg/m2 in other indications.
In recent years, several studies have investigated agents targeting the PD-(L)1 pathway in relapsed
cancer patients. Pembrolizumab is the only PD-(L)1 agent that has shown a significant OS benefit
compared with chemotherapy (vinflunine or taxanes) in a randomized phase 3 study and is
approved by the FDA for second-line treatment of locally advanced or metastatic urothelial
carcinoma.
Thus, the choice of vinflunine, the taxane docetaxel, and pembrolizumab as comparators to
erdafitinib is supported by current treatment practice and international guidelines.
3.2.2. 
Two-cohort Design
With the approval and subsequent increased use of agents targeting the PD-(L)1 pathway in the
front-line setting, 2 subgroups of relapsing patients are emerging: patients who have been treated
with an anti-PD-(L)1 and patients who have not been exposed to an anti-PD-(L)1. Pembrolizumab
has shown superior survival results over vinflunine or taxanes in the second-line setting. Moreover,

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the above described results with chemotherapy and pembrolizumab were obtained in a population
that was not preselected for the presence of FGFR gene aberrations. It is unclear whether the
presence or absence of FGFR gene aberrations affects the response to chemotherapy or
anti-PD-(L)1, and whether such an effect would differ according to the treatment received.
Urothelial cancer, like breast cancer, may be classified by gene expression signature into basal
versus luminal subtypes. The 2 subtypes may be further subdivided into 3 to 5 classifications
depending on which of several published gene signature algorithms are applied. Luminal tumors
are generally sub-classified into 2 subgroups: (1) Luminal 1, Luminal Papillary, or Urobasal A;
and (2) Luminal 2, Luminal Infiltrated, p53-like, or Genomically Unstable. The Basal subtype is
sub-classified into: Squamous Cell Carcinoma Like, Urobasal B, and Infiltrated (Lund model); or
Basal and Immune Undifferentiated, or Cluster III and Cluster IV for the Broad and TCGA models,
respectively (TCGA 2014, Choi 2014, Damrauer 2014, Choi 2017, Seiler 2017, Lerner 2017).
Bladder cancer subtype may inform patient prognosis and response to treatment, including
response to neoadjuvant chemotherapy (Choi 2014, Seiler 2017). These subtypes may be enriched
for specific mutations thought to contribute to their specific clinical features and biology (Choi
2017).
The Luminal 1 tumors are reported to be enriched for FGFR3 mutations, and lacking in immune
marker expression and immune cell infiltrate (Choi 2017). Differential response to immunotherapy
has been observed across bladder cancer subtypes, with the Luminal 1 subtype showing the lowest
response rate to the anti-PD-(L)1 inhibitors atezolizumab and nivolumab compared with other
bladder cancer subtypes (Rosenberg 2016, Sharma 2017).
Exploratory analyses of the atezolizumab phase 2 data show a clear differential response
depending on the subtypes of urothelial cancer. PD-(L)1 expression on tumor infiltrating immune
cells was more pronounced in the basal subtype (TCGA clusters III and IV) as compared to the
luminal subtype (TCGA clusters I and II or Luminal 1 and Luminal 2). PD-(L)1 high expression
was almost exclusively seen in the basal subtype. Response to atezolizumab was significantly
higher in the Luminal 2 subtype as compared to the other subtypes, with lowest objective response
rates in Luminal 1 and basal TCGA cluster II subtypes (Rosenberg 2016). FGFR-aberrations are
most prevalent in the Luminal 1 subtype (TCGA 2014), the subtype with the poorest response to
atezolizumab, which might point towards a lower response potential to anti-PD-(L)1 in tumors
with FGFR-aberrations. This is consistent with our observation that subjects with FGFR-
aberrations included in the ongoing Phase 2 study BLC2001 had a limited response rate (<5%) to
prior anti-PD-(L)1 treatments compared with published response rates in first and second line for
those compounds (15% to 20%).
It has also been postulated that resistance to chemotherapy is associated with FGFR-4 upregulation
(Roidl 2009) or with activated FGFR-1 (Karajannis 2006). FGFR aberrations may therefore be
associated with differential response to treatment with either chemotherapy or immunotherapy.
Additionally, the 2 groups of patients who relapse following front-line treatment, ie, patients who
have been previously treated with an anti-PD-(L)1 and patients who have not been exposed to an
anti-PD-(L)1), could be different from each other, and response to second line treatment could

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accordingly be different as well. Therefore, to adequately assess the specific role of FGFR
alterations in these 2 groups, a design with 2 independent cohorts, one erdafitinib versus
chemotherapy and one versus pembrolizumab, is warranted.
3.2.3. 
Dosing Schedule for Erdafitinib
Erdafitinib will be provided as a tablet for oral administration and subjects will be instructed to
take 8 mg orally once daily for 21 days on a 21-day cycle, until disease progression, intolerable
toxicity, withdrawal of consent, or decision by the investigator to discontinue treatment. Treatment
will be up-titrated to 9 mg, maintained at 8 mg, or withheld, based on phosphate level measured
on Cycle 1 Day 14, and taking into account observed toxicity to that day, as described in detail in
Section 6.1.
The 8 mg starting dose was selected on the basis of pharmacokinetic (PK), pharmacodynamic and
clinical data, which is summarized below.
Pharmacokinetics: At the 8 mg dose, based on PK simulations, the expected mean unbound Cavg
plasma concentrations in subjects during the 28-day cycle period is 3.4 ng/mL. The mean unbound
average plasma concentration of urothelial cancer subjects with clinical activity (partial responses)
in the Phase 1 study was 2.5 ng/mL, which is also consistent with the preclinical target window.
Antitumor activity is anticipated to correlate with preclinical AUC for unbound drug (AUCu), and
at the 8 mg dose level, 90% of subjects will have unbound trough plasma concentrations and AUCu
levels within the target window (0.6 to 2.4 ng/mL) by Day 3. Thus, 8 mg daily is predicted to
generate continuously efficacious drug concentrations for the vast majority of subjects. The dosing
regimen was further refined considering pharmacodynamic markers (see Clinical Activity section).
Pharmacodynamics: Hyperphosphatemia is a common drug-induced toxicity for anti-FGFR
targeted agents due to renal tubular FGFR inhibition. This can serve as a pharmacodynamic marker
of drug activity. In the Phase 1 study EDI1001, dose-dependent elevations in serum phosphate
occurred in all subjects starting at 4 mg daily. Because this represents a target-mediated drug effect,
the completed Phase 1 study could select a dose regimen that consistently induced manageable
hyperphosphatemia but did not exceed a critical level requiring cessation of therapy. Data from
the Phase 1 study indicates that a phosphate increase of at least 35% over baseline level may be
associated with anti-tumor response. Therefore, a pharmacodynamic objective of 50% increase in
phosphate level over baseline was considered to be appropriate. Given the median phosphate level
of 3.6 mg/dL at baseline in the Phase 1 study, and of 3.3 mg/dL at baseline in the Phase 2 study
(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 g/dL (which is also 35% over the phosphate upper
limit of normal). Subjects achieving a phosphate level of less than 5.5mg/dL in the course of the
first cycle dosing period would be considered to have had inadequate PD effect and would be
candidates for dose escalation to 9 mg daily to achieve an optimum PD effect (phosphate above
5.5 mg/dL).
Clinical safety: The 8-mg daily dose is the continuous regimen that, based on modeling, would
likely be well tolerated without significant treatment interruptions (approximately 10% to 15%

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anticipated early interruptions) and for which the majority of subjects would tolerate the sustained
dose of 8 mg once daily. Escalation on Day 15 of the first treatment cycle of daily dose from 8 mg
once daily to 9 mg once daily in the subjects with both phosphate below 5.5 mg/dL (suboptimal
pharmacodynamic effect), and without significant drug related toxicity (Grade ≥2 toxicity or
Grade ≥1 central serious retinopathy or retinal pigment epithelial detachments) is unlikely to
significantly change the overall tolerability profile.
Moreover, the observed safety of the 9-mg daily dose in the completed Phase 1 study did not raise
concerns about prolonged hyperphosphatemia, and no soft-tissue calcification nor any electrolyte
disturbance or endocrine abnormalities were reported. Similarly, in the ongoing Phase 2 study no
such abnormalities were observed either. Therefore, a more insistent approach to up-titration can
be adopted, allowing up-titration in subjects whose Day 14 phosphate is below 7 mg/dL without
concurrent temporary use of phosphate binder treatment or Day 14 phosphate is 7-9 mg/dL with
concurrent temporary use of phosphate binder treatment.
Clinical activity: Assessment of clinical activity at the 6-mg dose and in up-titrated subjects at IA1
is limited by the paucity of treated subjects, but 3 PR were observed in 14 subjects with phosphate
level below 5.5 mg/dL and 4 PR in 7 subjects with phosphate level over 5.5 mg/dL, pointing to
the potential importance of attaining full pharmacodynamic effect. Hence the aim is to bring a
maximal number of subjects to the target phosphate of 7 to 9 mg/dL in order to attain maximal
sustained inhibition of target, and thereby allow for potential optimization of efficacy, given the
observed correlation thus far between clinical response and the pharmacodynamic effect on
phosphate. Selective dose escalation to 9 mg for optimization of the pharmacodynamic effect is
likely to increase the potential for clinical activity without significantly increasing dose
interruptions or toxicity. The appropriateness of the proposed dosing regimen was supported by
pharmacokinetic-pharmacodynamic simulations based on the modeling of phosphate levels: the
proposed regimen was able to achieve the serum phosphate target level of 5.5 mg/dL in the
majority of subjects, while reducing the number of unforeseen dose interruptions and dose
adaptations.
3.2.4. 
Blinding, Control, Study Phase/Periods, Treatment Groups
Randomization will be used to minimize bias in the assignment of subjects to treatment groups
within each cohort, to increase the likelihood that known and unknown subject attributes
(eg, demographic and baseline characteristics) are evenly balanced across treatment groups, and
to enhance the validity of statistical comparisons across treatment groups within each cohort.
3.2.5. 
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 (or chemotherapy, or
pembrolizumab). 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.

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3.2.6. 
Patient Reported Outcomes Research
Patient-reported outcome (PRO) 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. Based on the clinical presentation of patients
with bladder cancer and prior PRO research in bladder cancer clinical trials, the PRO endpoints of
interest include scales from the FACT-Bl (physical well-being, functional well-being, bladder
symptoms subscale), PGIS, and the EQ-5D-5L (utility value and visual analog scale). These PRO
measures will be administered to test the hypothesis that treatment with erdafitinib maintains
health-related quality of life as measured by time to symptom or functional deterioration by a
prespecified meaningful change threshold. PRO data will be collected as outlined in the Time and
Events Schedule to understand how the endpoints change over time, with treatment and with the
clinical state of the subject.
4. 
SUBJECT POPULATION
Screening for molecular eligibility may be performed at any time prior to randomization; for
details, see Section 9.1.2. Full study screening for molecular eligible subjects will be performed
within 30 days before administration of the study drug. Separate informed consent forms (ICFs)
may be used for molecular eligibility screening and full study screening. For subjects signing a
new full-study ICF for the purpose of undergoing a new tissue biopsy for molecular screening, the
30-day window starts with the first planned study-related procedure other than the tissue biopsy;
however, AEs will need to be collected from the time of full-study ICF sign off.
The inclusion and exclusion criteria for enrolling subjects in this study are described in the
following 2 subsections. If there is a question about the inclusion or exclusion criteria below, 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 11.2, Sample
Size Determination.
4.1. 
Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study:
1. 
≥18 years of age (or the legal age of consent in the jurisdiction in which the study is taking
place)
2. 
Histologic demonstration of transitional cell carcinoma of the urothelium. Minor
components (<50% overall) of variant histology such as glandular or squamous
differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or
micropapillary change are acceptable
3. 
Criterion amended per Amendment 2:
3.1 Metastatic or surgically unresectable urothelial cancer

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4. 
Documented progression of disease, defined as any progression that requires a change in
treatment, prior to randomization
5. 
Criterion modified per Amendment 3:
5.1 Criterion modified per Amendment 4:
5.2. Criterion modified per Amendment 5:
5.3 Cohort 1: Prior treatment with an anti-PD-(L)1 agent as monotherapy or as
combination therapy; no more than 2 prior lines of systemic treatment. Prior treatment
with an anti-PD-(L)1 agent could have been given as neo-adjuvant, adjuvant, or in
metastatic line of treatment as frontline or maintenance therapy, as follows:
 Together with chemotherapy or as maintenance therapy
 Together with chemotherapy in metastatic setting
 For superficial cancer (early disease/non-muscle invasive bladder cancer), OR in
neo-adjuvant OR adjuvant setting. If these subjects did not relapse within a year
of their last dose of anti-PD-(L)1, this will not be counted as a prior line of
systemic treatment. These subjects will however still be eligible only for
Cohort 1.
Cohort 2: No prior treatment with an anti-PD-(L)1 agent; only 1 line of prior systemic
treatment.
Note: Subjects who received neoadjuvant or adjuvant chemotherapy or immunotherapy
and showed disease progression within 12 months ofthe last dose are considered to have
received systemic therapy in the metastatic setting.
6. 
Criterion modified per Amendment 4:
6.1 Subjects must meet appropriate molecular eligibility criteria, as determined by central
laboratory screening or by local historical test results (from tissue or blood) performed at
a Clinical Laboratory Improvement Amendments (CLIA)-certified or regional equivalent
laboratory using the following methods: local next-generation sequencing (NGS), direct
digital counting methods, or the Qiagen Therascreen FGFR Rotor-Gene Q (RGQ) reverse
transcription polymerase chain reaction (RT-PCR) test; see Section 9.1.2 for details.
Tumors must have at least 1 of the following translocations: FGFR2-BICC1, FGFR2-
CASP7, FGFR3-TACC3, FGFR3-BAIAP2L1; or 1 of the following FGFR3 gene
mutations: R248C, S249C, G370C, Y373C.
7. 
ECOG performance status Grade 0, 1, or 2 (Attachment 1)
8. 
Criterion amended per Amendment 2:
8.1 Criterion modified per Amendment 3:

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8.2 Criterion modified per Amendment 4:
8.3 Criterion modified per Amendment 5:
8.4 Adequate bone marrow, liver, and renal function:
a. Bone marrow function (without the support of cytokines or erythropoiesis-stimulating
agent in preceding 2 weeks):
 
Absolute neutrophil count (ANC) >1,500/mm3
 
Platelet count >75,000/mm3 (≥100,000/mm3 for Cohort 1 subjects at sites
choosing vinflunine chemotherapy)
 
Hemoglobin >8.0 g/dL (without transfusion or demonstrate stability, ie; no
significant decline in hemoglobin, for 2 weeks after transfusion)
b. Liver function:
 
Total bilirubin ≤1.5 x institutional upper limit of normal (ULN) OR direct
bilirubin ≤ULN for subjects with total bilirubin levels >1.5xULN [≤1xULN for
Cohort 1 subjects at sites choosing docetaxel chemotherapy]
 
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5x
institutional ULN or ≤5x institutional ULN for subjects with liver metastases
(For subjects in Cohort 1 at sites choosing docetaxel chemotherapy, both the
ALT and AST values must be ≤1.5×ULN concomitant with alkaline phosphatase
of ≤2.5×ULN)
c. Renal function: Creatinine clearance (CrCl) >30 mL/min either directly measured via
24-hour urine collection or calculated using the Cockcroft-Gault formula
(Attachment 2).
d. Criterion deleted per amendment 3.
e. Phosphate: <ULN within 14 days of treatment and prior to Cycle 1 Day 1 (medical
management allowed)
9. 
Criterion amended per Amendment 3:
9.1 Must sign an informed consent form (ICF) (or their legally acceptable representative
must sign) indicating that he or she understands the nature, significance, purpose of,
procedures for, and consequences of the study and is willing to participate in the study.
10. 
A woman of childbearing potential who is sexually active must have a negative pregnancy
test (-human chorionic gonadotropin [hCG]) at Screening (urine or serum).
11. 
Criterion amended per Amendment 2:
11.1 Criterion amended per Amendment 3:
11.2 Contraceptive use by men or women should be consistent with local regulations
regarding the use of contraceptive methods for subject participating in clinical studies.

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For women of childbearing potential (defined as: fertile, following menarche and until
becoming post-menopausal unless permanently sterile. Permanent sterilization methods
include hysterectomy, bilateral salpingectomy and bilateral oophorectomy):
 
practicing 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; 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 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
 
agrees to remain on a highly effective method of contraception during the study and
for at least 6 months after the last dose of study drug
 
agrees to not donate eggs (ova, oocytes) for the purposes of assisted reproduction
during the study and for at least 6 months after the last dose of study drug
 
not breastfeeding and not planning to become pregnant during the study and for at
least 6 months after the last dose of study drug
For men who are sexually active with women of childbearing potential:
 
agrees to use a condom with spermicidal foam/gel/film/cream/suppository
 
agrees to not donate sperm during the study and for at least 6 months after the last
dose of study drug
 
not planning to father a child during the study or within 6 months after the last dose
of study drug
4.2. 
Exclusion Criteria
4.2.1. 
Exclusion Criteria for All Subjects
Any potential subject who meets any of the following criteria will be excluded from participating
in the study:
1. 
Treatment with any other investigational agent or participation in another clinical study
with therapeutic intent within 30 days prior to randomization.

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2. 
Criterion amended per Amendment 2:
2.1 Criterion modified per Amendment 3:
2.2 Active malignancies (ie, requiring treatment change in the last 24 months). The only
allowed exceptions are:
 
urothelial cancer.
 
skin cancer treated within the last 24 months that is considered completely cured.
 
localized prostate cancer with a Gleason score of 6 (treated within the last
24 months or untreated and under surveillance).
 
localized prostate cancer with a Gleason score of 3+4 that has been treated more
than 6 months prior to full study screening and considered to have a very low risk
of recurrence.
3. 
Symptomatic central nervous system metastases.
4. 
Received prior FGFR inhibitor treatment.
5. 
Known allergies, hypersensitivity, or intolerance to erdafitinib or its excipients
6. 
Criterion amended per Amendment 2:
6.1 Criterion modified per Amendment 3.
6.2 Current central serous retinopathy (CSR) or retinal pigment epithelial detachment
of any grade.
7. 
History of uncontrolled cardiovascular disease including:
a. unstable angina, myocardial infarction, ventricular fibrillation, Torsades de Pointes,
cardiac arrest, or known congestive heart failure Class III-V (Attachment 3) within
the preceding 3 months; cerebrovascular accident or transient ischemic attack within
the preceding 3 months.
b. QTc prolongation as confirmed by triplicate assessment at screening (Fridericia;
QTc >480 milliseconds).
c. Pulmonary embolism or other venous thromboembolism (VTE) within the
preceding 2 months.
8. 
Known active 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.
9. 
Criterion amended per Amendment 3:

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9.1 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).
10. 
Criterion amended per Amendment 3:
10.1 Not recovered from reversible toxicity of prior anticancer therapy (except toxicities
which are not clinically significant such as alopecia, skin discoloration, neuropathy,
hearing loss).
11. 
Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers,
known gastric ulcers, or unhealed incisions.
12. 
Major surgery within 4 weeks before randomization.
13. 
Criterion amended per Amendment 2:
13.1 Criterion modified per Amendment 3:
13.2 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.
4.2.2. 
Exclusion Criteria for Cohort 1 Subjects
In addition to the exclusion criteria listed above, any potential subject in Cohort 1 who meets the
following criterion will be excluded from participating in the study:
14. 
Criterion amended per Amendment 2:
14.1 Criterion modified per Amendment 3:
14.2 Criterion modified per Amendment 4:
14.3 For those participating at sites using docetaxel: has a history of severe
hypersensitivity reaction (eg, generalized rash/erythema, hypotension, bronchospasm,
angioedema or anaphylaxis) to either docetaxel or to other drugs formulated with
polysorbate and paclitaxel. At sites using docetaxel, subjects with evidence of
interstitial lung disease or active non-infectious pneumonitis are excluded.
4.2.3. 
Exclusion Criteria for Cohort 2 Subjects
In addition to the exclusion criteria listed above, any potential subject in Cohort 2 who meets any
of the following criteria will be excluded from participating in the study:
15. 
Active autoimmune disease requiring systemic treatment within the past 3 months or a
documented history of clinically severe autoimmune disease, or a syndrome that
requires systemic or immunosuppressive agents. Subjects with vitiligo, diabetes Type I,
or resolved childhood asthma/atopy would be an exception to this rule. Subjects who

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require intermittent use of bronchodilators, inhaled steroids, or local steroid injections
are not excluded from the study. Subjects with hypothyroidism stable on hormone
replacement or Sjøgren's syndrome will not be excluded from the study.
16. 
Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other
form of immunosuppressive therapy within 7 days prior to the first dose of study
treatment. The use of physiologic doses of corticosteroids may be approved after
consultation with the sponsor.
17. 
Evidence of interstitial lung disease or active non-infectious pneumonitis.
18. 
Active infection requiring systemic therapy.
19. 
Received a live virus vaccine within 30 days of first dose.
20. 
Known allergies, hypersensitivity, or intolerance to pembrolizumab or its excipients.
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 he or she no longer meets all eligibility criteria, then the subject should be excluded from
participation in this study. Section 9.1.2 describes options for retesting. Section 17.4 describes the
required documentation to support meeting the enrollment criteria.
5. 
TREATMENT ALLOCATION AND BLINDING
Treatment Allocation
Central randomization will be implemented in this study. Subjects will be assigned to Cohort 1 or
Cohort 2 based upon prior treatment with anti-PD-(L)1 agent. Within each cohort, subjects will be
randomly assigned to 1 of 2 treatment groups based on a computer-generated randomization
schedule prepared before the study by or under the supervision of the sponsor. The randomization
will be balanced by using randomly permuted blocks and will be stratified by region (North
America vs EU vs rest of world), Eastern Cooperative Oncology Group (ECOG) performance
status (0 or 1 vs 2), and disease distribution (presence vs. absence of visceral metastases: lung,
liver, or bone). The interactive web response system (IWRS) will assign a unique treatment code,
which will dictate the treatment assignment and matching study drug kit for the subject. The
requestor must use his or her own user identification and personal identification number when
contacting the IWRS and will then give the relevant subject details to uniquely identify the subject.
6. 
DOSAGE AND ADMINISTRATION
6.1. 
Erdafitinib
Erdafitinib will be provided as tablets for oral administration. Subjects randomized to Arm 1A and
Arm 2A will be instructed to take erdafitinib orally, at a starting dose of 8 mg, once daily for
21 days in a 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent or

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decision by the investigator to discontinue treatment. 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 and subjects should not
attempt to dissolve them in water, tablets must not be broken or chewed. Subjects should avoid
consuming grapefruit or Seville oranges due to CYP450 3A4/5 inhibition.
Up-titration Guidelines
All subjects will start erdafitinib 8 mg once daily from Day 1 to Day 14 of Cycle 1. On Day 14 of
Cycle 1, a blood sample will be drawn to determine serum phosphate concentration.
 
Subjects with serum phosphate levels 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 4 for detailed guidelines regarding further treatment).
 
Subjects with serum phosphate levels between 7.00 to 8.99 mg/dL (2.25 mmol/L to
2.90 mmol/L) should increase the erdafitinib dose to 9 mg once daily, while concurrently
initiating treatment with a phosphate binder such as sevelamer (see Table 4 for details).
 
Subjects with 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.
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).
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).
6.1.1. 
Dose Modifications and Dose Delays for Erdafitinib
Treatment with erdafitinib should be discontinued or modified based on toxicity as described in
Table 1. For eye, skin/nail, dry mouth/mucositis, and phosphate toxicity, specific
recommendations in the management guidelines are provided in Section 6.1.2.

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Table 1: 
Erdafitinib Dose Modification Rules Based on Erdafitinib-related Toxicity
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 lowerb if not
completely resolved to baseline (but resolved to Grade 1).
3 
Interrupt drug 
Restart at 1 dose lowerb if recovered to baseline (to ≤Grade 1 or
back to baseline for non-hematologic toxicity) within 28 days;
restart at 2 doses lowerb if not completely resolved to baseline
(but resolved to Grade 1) within 28days. Discontinue drug if
unresolved for >28 days.
4 
Interrupt drug 
Discontinue.
a 
For eye, skin/nail, dry mouth/mucositis, and phosphate toxicity please follow specific recommendations in the
management guidelines (Section 6.1.2).
b 
Please refer to Table 2.
 
Subjects with any grade of toxicity (Grade 1 to 4) should be provided symptomatic treatment
where applicable.
 
If erdafitinib is interrupted consecutively for 1 week or longer due to drug-related toxicity, the
study drug may be reintroduced at either the same dose level or the first reduced dose level
following recovery from the toxicity (see dose reduction levels in Table 2). A second dose
reduction may be implemented following a second occurrence of drug-related toxicity.
 
If erdafitinib must be withheld for more than 28 days for a drug-related adverse event that
fails to resolve to acceptable level (eg, ≤Grade 1 non-hematologic toxicity or back to
baseline), treatment with erdafitinib should be discontinued except when the subject has been
deriving benefit from treatment, and the investigator can demonstrate that continued treatment
with erdafitinib is in the best interest of the subject. Erdafitinib may be re-started at the same
or a lower dose (Table 2) if the sponsor’s medical monitor concurs with the assessment.
 
If erdafitinib was dose-reduced and the adverse event that was the reason for this dose-
reduction has completely resolved, the dose may be re-escalated to the next higher dose ifthe
subject was deriving benefit from treatment, and the investigator can demonstrate that dose
re-escalation of erdafitinib is in the best interest of the subject and the sponsor’s medical
monitor concurs with the assessment.
 
In all cases of clinically significant impaired wound healing or imminent surgery or potential
bleeding complications, it is recommended that dose administration be interrupted,
appropriate clinical laboratory data (eg, coagulation parameters) be carefully monitored, and
supportive therapy administered, where applicable. Dose administration may be restarted
when it is considered safe and at an appropriate dose, according to the investigator’s
assessment.

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Table 4: 
Guidelines for Management of Serum Phosphate Elevation
Serum Phosphate
Level 
Study Drug Management 
Symptom Management
9.00 10.00 mg/dL 
(2.91 3.20 mmol/L) 
(Grade 3)
Withhold b 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.
Phosphate binders (eg,
sevelamer up to 1,600 mg TID
with food) until serum
phosphate level is <7.00 mg/dL.
(See information regarding
phosphate binders other than
sevelamer in the table footnote.)
>10.00 mg/dL 
(>3.20 mmol/L) 
(Grade 4)
Withhold b 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 
function or Grade 3 
hypocalcemia 
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 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 6.1.1.)
Medical management as
clinically appropriate.
TID 3 times a day.
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. Study drug interruptions for hyperphosphatemia suggested to be 7 days in duration.
6.1.2.3. 
Guidelines for the Management of Dry Mouth and Mucositis
Guidelines for the clinical management of dry mouth (xerostomia) and mucositis are provided in
Table 5 and Table 6, respectively.
 
General Prophylaxis:
 
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)

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Table 5: 
Guidelines for Management of Dry Mouth (Xerostomia)
Grade and Definition 
Study Drug Management 
Symptom Management
Grade 1: symptomatic (eg, dry or 
thick saliva) without significant 
dietary alteration; unstimulated saliva
flow >0.2 mL/min
Continue study drug 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 study drug at current dose. 
Sorbitol lozenges as
needed and Cevimiline 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 study drug (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 Cevimiline 30
mg TID or Pilocarpine 5
mg TID, orally
Grade 4: life-threatening 
consequences, urgent intervention 
indicated
Discontinue study drug. 
Evaluation and therapy as
clinically indicated
Table 6: 
Guidelines for the Management of Oral Mucositis
Grade 
Study Drug Management 
SymptomManagement
Grade 1 Continue study drug 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 study drug if the subject has 
other study-drug related concomitant Grade 2 
AEs. 
 Hold study drug 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 study drug 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.
Grade 3  Hold study drug, with reassessments ofclinical 
condition in 1-2 weeks. 
 When resolves to ≤Grade 1 or baseline, restart 
at 1 dose level belowin 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 studydrug. 
Evaluation and therapyas clinically indicated.
AE=adverse event; QID= four times a day.

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6.1.2.4. 
Guidelines for the Management of Dry Skin and Skin Toxicity
Guidelines for the management of dry skin are provided in Table 7.
 
General prophylaxis:
 
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%).
Table 7: 
Guidelines for Management of Dry Skin
Grade and Definition 
Study Drug Management 
Symptom Management
Grade 1: Dry skin covering less 
than 10% body surface area (BSA) 
and no associated erythema or 
pruritus 
Continue study drug 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 study drug 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 study drug (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 study drug. 
Evaluation and therapy as clinically
indicated
*Topical Steroid Ointments: Clobetasol 0.05%, Betamethasone 0.05%, Fluocinonide 0.05%

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6.1.2.5. 
Guidelines for Management of Nail Toxicity (Onycholysis,
Onychodystrophy, and Paronychia)
Guidelines for management of nail discoloration/loss/ridging (onycholysis/onychodystrophy) are
provided in Table 8. Guidelines for the management of paronychia are provided in Table 9.
 
General Prophylaxis:
 
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 8: 
Guidelines for Management of Nail Discoloration/Loss/Ridging (Onycholysis/
Onychodystrophy)
Grade 
Study Drug Management 
SymptomManagement
Grade 1 
Continue study drug at current dose. 
 Continue general prophylaxis recommendations
 Over-the-counter nail strengthener OR poly-urea
urethane nail lacquer (Nuvail) OR diethylene
glycol monoethylether nail lacquer (Genadur)
daily.
 Use non-alcohol-containing moisturizing creams.
Grade 2 
Consider holding study drug 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/ureaointmentdaily)
 Silver nitrate application weekly AND topical
antibiotics AND vinegar soaksa
Grade 3 
Hold study drug, 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/trimethoprimBID).
For cases ofsevere/refractoryinfection consider
intravenousantibiotics.
Consider dermatological orsurgical evaluation.
Grade 4 
Discontinue study drug. 
Evaluation and therapyas clinicallyindicated.
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/polymixin B.
BID=bis in die (two times each day).

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Table 9: 
Guidelines for Management of Paronychia
Grade 
Study Drug Management 
Symptom Management
Grade 1 
Continue study drug at current 
dose. 
Topical antibiotics AND vinegar
soaksa
Grade 2 
Continue study drug at current 
dose. 
Consider study drug 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 study drug (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
6.1.2.6. 
Guidelines for Eye Toxicity Associated with Vision Changes
If a subject experiences an event of confirmed new corneal or retinal abnormality while on study
drug, the event should be reported as an adverse event or a serious adverse event (if Grade 3 or
higher) as appropriate. 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 below.
Amsler Grid (illustrated in Attachment 4): 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.

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Table 10: 
Guidelines for Management of Eye Toxicity
Grade and Definition  
Study Drug 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
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.
Grade 3: Severe or 
medically significant 
but not immediate sight  
threatening; 
hospitalization or 
prolongation of existing 
hospitalization 
indicated; disabling;
limiting self care ADL
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 drug 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.

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Table 10: 
Guidelines for Management of Eye Toxicity
Grade and Definition  
Study Drug Management 
Symptom Management
Grade 4: Sight  
threatening
consequences; urgent
intervention indicated;
blindness (20/200 or 
worse) in the 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
6.1.2.7. 
Guidelines for the Management of Dry Eye
 
General considerations: Avoid unnecessary exposure to sunlight, use sunglasses in bright
light.
 
Prophylactic management: Frequent use of artificial tear substitutes and ocular demulcents
is strongly recommended.
 
Reactive management:
 
Withhold erdafitinib for Grade 3 toxicity
 
Artificial tear substitutes if not started, every 4 to 6 hours
 
Ocular demulcents
 
Severe treatment-related dry eye should be evaluated by an ophthalmologist
6.2. 
Vinflunine or Docetaxel
Subjects randomized to chemotherapy in Arm 1B will receive vinflunine 320 mg/m2 as a
20-minute intravenous infusion once every 3 weeks or docetaxel 75 mg/m2 as a 1-hour intravenous
infusion every 3 weeks. Treatment with either agent will be administered until disease progression,
intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment.
The choice of which chemotherapy regimen to use at each site will be determined by the
investigator.
In cases where toxicity does not resolve to Grade 0-1 within 2 weeks after the last infusion of
vinflunine or 4 weeks after the last infusion of docetaxel, study treatment should be discontinued
after consultation with the sponsor. With investigator and sponsor agreement, subjects with a
laboratory adverse event still at Grade 2 after 4 weeks may continue in the study only if
asymptomatic and stable.
6.2.1. 
Vinflunine
Vinflunine, 320 mg/m2, should be administered after all procedures and assessments for that day
have been completed as outlined in the Time and Events Schedule. The body surface area (BSA)
in m2 should be calculated per local institutional practice. Consult the vinflunine summary of
product characteristics for instructions on preparation and administration of the vinflunine infusion
fluid and recommendations for co-medication (ie, laxatives and dietary measures including oral
hydration are recommended from Day 1 to Day 7 after each vinflunine administration). Advice on

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conservation of sperm should be sought prior to treatment because of the possibility of irreversible
infertility due to therapy with vinflunine.
6.2.1.1. 
Vinflunine Dose Modifications
In case of WHO/ECOG performance status (PS) of ≥1 or PS of 0 and prior pelvic irradiation,
vinflunine treatment should be started at the dose of 280 mg/m². In the absence of any
hematological toxicity during the first cycle causing treatment delay or dose reduction, the dose
will be increased to 320 mg/m² every 3 weeks for the subsequent cycles.
In subjects with moderate renal impairment (40 ml/min≤CrCl≤60 ml/min), the recommended dose
is 280 mg/m² given once every 3 weeks. In subjects with  severe renal impairment
(20 mL/min≤CrCl<40 mL/min), the recommended dose is 250 mg/m² given once every 3 weeks.
The recommended dose of vinflunine is 250 mg/m² given once every 3 weeks in subjects with
mild liver impairment (Child-Pugh Grade A) or in subjects with a prothrombin time ≥60% normal
value and 1.5xULN<Bilirubin≤3xULN and presenting at least one of the following criteria:
transaminases >ULN or gamma-glutamyltransferase >5xULN.
The recommended dose of vinflunine is 200 mg/m2 given once every 3 weeks in patients with
moderate liver impairment (Child-Pugh grade B) or in patients with a prothrombin time ≥50%
normal value and bilirubin >3×ULN and transaminases >ULN and gamma-glutamyltransferase
>ULN.
The doses recommended in subjects ≥75 years old are as follows:
 
in subjects at least 75 years old but less than 80 years, the dose of vinflunine to be given is
280 mg/m² every 3 weeks.
 
in subjects 80 years old and beyond, the dose of vinflunine to be given is 250 mg/m² every
3 weeks.
In subjects who initiate vinflunine at 280 mg/m2 and who experience an AE requiring dose
modification, the dose should be reduced to 250 mg/m2 following the first occurrence and
resolution, and discontinued following a second occurrence. In subjects who initiate vinflunine at
250 mg/m2 and who experience an AE requiring dose modification, the dose should be reduced to
225 mg/m2 following the first occurrence and resolution, and discontinued following a second
occurrence.
Cases of posterior reversible encephalopathy syndrome (PRES) have been observed after
administration of vinflunine. The typical clinical symptoms are, as follows: neurological
(headache, confusion, seizure, visual disorders), systemic (hypertension), and gastrointestinal
(nausea, vomiting). Radiological signs are white matter abnormalities in the posterior regions of
the brain. Vinflunine should be discontinued in subjects who develop neurological signs of PRES.
For all grades of neutropenia lasting ≤7 days, hold vinflunine administration until neutrophils
recover to >1500 cells/mm3. For thrombocytopenia Grades 1, 2, 3, hold vinflunine until platelets

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recover to >100,000 cells/mm3. For anemia Grades 1, 2, 3, hold vinflunine until resolution to
Grade 1 or baseline. Specific dose modifications for subjects receiving vinflunine are
recommended in Table 11. Dose modifications for vinflunine should also be considered according
to local product labels.
Table 11: 
Vinflunine Dose Adjustments for Drug-related Adverse Events
Toxicity
Dose Adjustment
Initial Dose: Vinflunine 320 mg/m2
Initial Dose:
Vinflunine 280 mg/m2
First
Occurrence
Second
Occurrence
Third
Occurrence
First 
Occurrence 
Second
Occurrence
Neutropenia Grade 4 lasting >7 days
(hold treatment until neutrophils
>1500 cells/mm3)
Vinflunine 
280 mg/m2 
Vinflunine 
250 mg/m2 
Discontinue 
treatment 
Vinflunine 
250 mg/m2 
Discontinue
treatment
Thrombocytopenia Grade 4 (hold
treatment until platelets >100,000
cells/mm3)
Anemia Grade 4 (hold treatment
until Grade 1 or baseline)
All other Grade 3 or 4 toxicities
(hold treatment until Grade 1 or
baseline)
Neutropenic fever (Temperature
≥100.5oF and ANC≤1000/L)
Mucositis or constipation Grade 2
≥5 days or Grade ≥3 any duration a
Cardiac ischemia in subjects with
prior history of myocardial infarction
or angina pectoris
Discontinue
treatment 
N/A  
N/A
Discontinue
treatment
N/A
a. NCI CTC Grade 2 constipation is defined as requiring laxatives, Grade 3 as an obstipation requiring manual
evacuation or enema, Grade 4 as an obstruction or toxic megacolon. Mucositis Grade 2 is defined as
“moderate”, Grade 3 as “severe” and Grade 4 as “life-threatening”
6.2.2. 
Docetaxel
Docetaxel, 75 mg/m2, should be administered after all procedures and assessments for that day
have been completed as outlined in the Time and Events Schedule. The body surface area (BSA)
in m2 should be calculated per local institutional practice. All subjects should be premedicated
with oral corticosteroids, such as dexamethasone 16 mg per day (eg, 8 mg twice daily) for 3 days
starting 1 day prior to docetaxel administration in order to reduce the incidence and severity of
fluid retention as well as the severity of hypersensitivity reactions. The appropriate premedication
regimen may be determined by the investigator.
Cystoid macular edema has been reported in subjects treated with docetaxel. Subjects with
impaired vision should undergo a prompt and complete ophthalmologic examination. In case
cystoid macular edema is diagnosed, docetaxel treatment should be discontinued and appropriate
treatment initiated.
Consult the docetaxel prescribing information for instructions on preparation and administration
of the docetaxel infusion fluid, and recommendations for co-medication.

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6.2.2.1. 
Docetaxel Dose Modifications
Docetaxel should not be given to subjects with bilirubin >1x ULN, or to subjects with AST or
ALT >1.5 x ULN with concomitant alkaline phosphatase >2.5 x ULN. Subjects with elevations of
bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased
risk for the development of Grade 4 neutropenia, febrile neutropenia, infections, severe
thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death. Docetaxel should also
not be given to subjects with a neutrophil count of <1500 cells/mm3.
Severe fluid retention has been reported following docetaxel therapy. Subjects should be
premedicated with oral corticosteroids prior to each docetaxel administration to reduce the
incidence and severity of fluid retention. Subjects with pre-existing effusions should be monitored
closely from the first dose for the possible exacerbation of the effusions. Subjects developing
peripheral edema may be treated with standard measures, eg, salt restriction, oral diuretic(s).
For all grades of neutropenia lasting ≤7 days, hold docetaxel until neutrophils recover to
>1500 cells/mm3. For thrombocytopenia Grades 1, 2, 3, hold docetaxel until platelets recover to
>100,000 cells/mm3. For anemia Grades 1, 2, 3, hold docetaxel until resolution to Grade 1 or
baseline. Dose modifications for subjects receiving docetaxel are recommended below in Table 12.
Dose modifications for docetaxel should also be considered according to local product labels.

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pembrolizumab, administration of corticosteroids, and/or supportive care. Immune-related adverse
reactions may also occur after the last dose of pembrolizumab. Immune-related adverse reactions
affecting more than 1 body system can occur simultaneously.
For suspected immune-related adverse reactions, adequate evaluation to confirm etiology or
exclude other causes should be ensured. Please refer to the pembrolizumab prescribing information
for specific instructions on how to assess and manage specific immune-related adverse reactions,
including pneumonitis, colitis, hepatitis, endocrinopathy, cutaneous, and other adverse reactions.
Consult the pembrolizumab prescribing information for instructions on preparation and
administration of the pembrolizumab infusion fluid.
6.3.1. 
Pembrolizumab Dose Modifications
For dose modifications for pembrolizumab and management of pembrolizumab related adverse
events, please refer to the prescribing information.
6.4. 
Continued Access to Study Drug after the End of Data Collection
Timepoint
Subjects may have continued access to study drug on this study in the LTE Phase. The continuation
of study drug after the end of data collection timepoint (Section 17.9.1, Attachment 8) is as follows:
 
Erdafitinib (Cohorts 1 and 2): Subjects in each cohort who are continuing to derive benefit
from erdafitinib as determined by their investigator may continue to receive erdafitinib.
Provision of erdafitinib may continue until the subject can commercially access study
treatment within the local healthcare system, until the investigator decides it is in the best
interest of the subject that erdafitinib be discontinued, or until 2 years after local marketing
authorization is obtained for the studied indication, whichever comes first. Also, the Sponsor
will not provide continued erdafitinib treatment if the final analysis for the respective cohort
does not show superiority for erdafitinib treatment, unless the investigator determines that the
subject is benefitting from erdafitinib and decides that treatment should be continued. Plans
for continued access stated in this protocol may change if new information on the benefit-risk
profile of the study drugs becomes available during the study or program.
 
Pembrolizumab (Cohort 2): For subjects who are continuing to derive benefit from
pembrolizumab, provision of pembrolizumab may continue until 2 years after the first dose
of pembrolizumab (at start of study) or until the subject can commercially access
pembrolizumab within the local healthcare system, whichever comes first.
 
Chemotherapy (docetaxel and vinflunine, Cohort 1): Subjects who are continuing to derive
benefit from chemotherapy will be switched to commercially supplied chemotherapy within
the local healthcare system (outside of this study), at or shortly after the end of data collection
timepoint. Provision of chemotherapy may continue in the LTE Phase of this study until the
subject can commercially access chemotherapy within the local healthcare system.
After the end of data collection timepoint, only serious adverse events will be reported to the
Company safety repository when study drug is supplied by the Sponsor.

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Also, in the event of a decision by the Sponsor to allow cross-over to erdafitinib following the final
analysis for each respective cohort, investigators will be notified (see Attachment 8 for more
details).
7. 
TREATMENT COMPLIANCE
The investigator or designated study personnel will maintain a log of the amount of study drug
(erdafitinib, vinflunine, docetaxel, or pembrolizumab) dispensed and returned. Drug supplies will
be inventoried and accounted for throughout the study.
Subjects will receive instructions on compliance with study treatment at the screening visit. 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 course of 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.
8. 
CONCOMITANT THERAPY
Concomitant therapies 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 CRF.
All therapies (prescriptions or over the counter medications) continued at the start of the study or
started during the study and different from the study drug must be documented in the concomitant
therapy section of the CRF. Caution should be exerted for subjects taking anti-coagulant therapies
(see Section 8.3). 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.
8.1. 
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
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.

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Chronic supportive therapies: Ongoing bisphosphonates and denosumab or other supportive
therapies are permitted.
 
Palliative radiotherapy: Localized radiotherapy for symptomatic control is permitted, but
should not include definitive radiation to target lesions.
8.2. 
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
 
Concurrent antineoplastic agents or hormonal anticancer therapy
 
For subjects in Arm 1B (both vinflunine and docetaxel):
 Strong inhibitors of the CYP3A4 enzymes. Strong inducers of CYP3A4 should be
avoided for subjects receiving vinflunine (see Attachment 5 for strong or moderate
CYP3A4 inhibitors and inducers).
 Live vaccines within 30 days prior to the first dose and while participating in the study,
and for 3 months following the last dose of study therapy. Examples of live vaccines
include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster,
yellow fever, intranasal influenza, rabies, BCG, and typhoid vaccine
 
For subjects in Arm 1B (vinflunine only): QT/QTc prolonging drugs
 
For subjects in Arm 2B (pembrolizumab):
 
Live vaccines within 30 days prior to the first dose and while participating in the study
and for 3 months following the last dose of study therapy.
 
Glucocorticoids for any purpose other than to modulate symptoms from an event of
clinical interest of suspected immunologic etiology. The use of physiologic doses of
corticosteroids may be approved after consultation with the sponsor.
8.3. 
Precautions for Concomitant Medications
The following precautions are advised for subjects in Arms 1A and 2A (erdafitinib):
 
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% to 34% when co-administered with itraconazole (a strong inhibitor
of CYP3A4) and 21% to 49% 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 Attachment 5). Consider alternative therapies that are not strong
inhibitors of CYP3A4 or moderate inhibitors of CYP2C9 during treatment with erdafitinib. If
co-administration of these drugs is unavoidable, monitor the subject closely for adverse
reactions and consider dose modifications accordingly. If the strong inhibitor of CYP3A or
moderate inhibitor of CYP2C9 is discontinued, the erdafitinib dose may be increased in the
absence of drug-related toxicity.

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The impact of moderate CYP2C9 inducers and strong CYP3A4 inducers (such as rifampin)
on erdafitinib was not clinically studied. Co-administration of erdafitinib with these agents
may significantly decrease erdafitinib exposure. Therefore, the concomitant use of these
agents with erdafitinib should be avoided (see Attachment 5). Co-administration of erdafitinib
with moderate CYP3A inducers may decrease erdafitinib exposure. Caution should be
exercised for concomitant administration of erdafitinib and moderate inducers of CYP3A4
(see Attachment 5).
 
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. Therefore, caution should be exercised for co-administered drugs that
are 
P-gp 
substrates, 
such 
as 
digoxin, 
dabigatran, 
and 
fexofenadine
(https://www.fda.gov/downloads/drugs/guidances/ucm292362.pdf); in addition, drugs with a
narrow therapeutic index should only be used where the benefit outweighs the potential risk.
 
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. Caution should be exercised considering the risk benefit ratio, and more frequent
monitoring of phosphate levels during treatment with medications known to increase the
serum level of phosphate put in place.
9. 
STUDY EVALUATIONS
9.1. 
Study Procedures
9.1.1. 
Overview
The Time and Events Schedule 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 to be collected will vary depending on the number
of cycles of the study drug that the subject receives. The maximum amount of blood to be drawn
from each subject is estimated to be approximately 30 mL at screening, approximately 300 mL
over the course of the first 6 months (8cycles) of treatment, then approximately 455 mL if the
subject remains on treatment for a period of 2 years, and approximately 45 mL at the
End-of-Treatment. Unscheduled blood samples may be required for safety issues of individual
subjects.
9.1.2. 
Screening Phase
The Screening Period will consist of a molecular eligibility screening period and a full study
screening period. The molecular eligibility assessment period starts with obtaining consent using
the Molecular Eligibility Testing Informed Consent Form (ICF) or, if a biopsy is required, the
Full-Study ICF, and may occur at any time prior to randomization. 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. Archival

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tumor tissue or a fresh biopsy sample will be sent to the central laboratory to be analyzed with an
investigational device, even if local FGFR test results are available. Tissue suitable for FGFR
testing must be taken from either a metastatic site or from a urothelial tract region or a lesion that
is T2 or above. If a fresh biopsy is needed, the subject will sign the full study ICF.
Molecular eligibility can be confirmed using either central or local FGFR test results.
(1) Central Screening: the central laboratory will evaluate subjects for molecular eligibility by
analyzing tumor specimens for the presence of selected FGFR gene mutations and translocations.
The sponsor or central laboratory/designee will communicate results of the molecular eligibility
testing to the site. If a subject meets the molecular eligibility criteria, he or she may continue study
screening under the Full-Study ICF for determination of the full-study eligibility. Subjects may
by-pass the molecular screening phase of BLC3001 if they have already been molecularly screened
by the central laboratory in the context of another Janssen-sponsored study.
(2) Local report with evidence of a study-eligible FGFR mutation or translocation: local historical
test results (from tissue or blood) performed at a CLIA-certified or regional equivalent laboratory
using the following methods may be used to meet molecular eligibility: local NGS, direct digital
counting methods, or the Qiagen Therascreen FGFR RGQ RT-PCR test. The Sponsor must
confirm eligibility based on local testing prior to entering full study screening.
 
If a subject is enrolled based on local historical testing, a tissue sample must still be submitted
at the time of enrollment for retrospective confirmation of FGFR  status, diagnostic
development, and biomarker research. If tissue specimens are not available for central
molecular screening, the site should contact the sponsor prior to proceeding to full study
screening.
 
The sponsor cannot authorize performance of high-risk fresh biopsies to obtain tissue for
retrospective central confirmation of FGFR status.
 
The results of retrospective central confirmation do not affect the subject’s eligibility for the
study. Results of retrospective confirmation studies will not be communicated to the site.
The Full Study Screening Period is 30 days before the first dose of study medication on Cycle 1
Day 1. Subjects must meet all of the inclusion and none of the exclusion criteria in Section 4. All
information required for randomization purposes must be available at the time of randomization
including: ECOG performance status, FGFR alteration type (translocation or mutation), disease
distribution (presence or absence of visceral metastases in the lung, liver or bone) based upon
baseline radiographic imaging performed during screening window, and prior therapy. 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.

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9.1.3. 
Treatment Phase
The Treatment Phase will begin with the administration of the first dose of erdafitinib, vinflunine,
docetaxel, or pembrolizumab and will continue until disease progression, intolerable toxicity,
withdrawal of consent, decision by the investigator to discontinue treatment, or study completion
(ie, the end of data collection timepoint has been achieved for the respective cohort). However,
treatment with study drug may continue after the end of the study data collection timepoint (see
Section 6.4 and Attachment 8). Subjects assessed with progressive disease, but for whom the
treating physician strongly believes that continuation of study treatment is in their best interest,
may be allowed to continue treatment with erdafitinib or pembrolizumab after consultation with
the medical monitor (please see guidelines in Section 9.2.2). The subject will continue to follow
procedures as outlined in the Time and Events Schedule and receive treatment until such time as
the treating physician and the medical monitor agree that further continuation of treatment is no
longer providing benefit to the subject. Subjects on erdafitinib, should follow the same visit
schedule even when the drug is interrupted.
Adverse events occurring any time after the subject signs the Full-Study ICF and up to 30 days
after the last dose of study drug are to be recorded for all subjects (no adverse events will be
collected for subjects signing the molecular ICF only). Adverse event information will be graded
using the National Cancer Institute Common Terminology Criteria for Adverse Events
(NCI-CTCAE), Version 4.03. See Section 12 for complete details on adverse event reporting.
Concomitant medications used will also be recorded throughout this time period.
Throughout the Treatment Period, the investigator will assess response to therapy using RECIST
Version 1.1. Efficacy evaluations are described in Section 9.2. 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.
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 Time and Events Schedule. All
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.
Additional information on reporting of adverse events is provided in Section 12.
9.1.4. 
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 study completion (ie, the end of
data collection timepoint has been achieved for the respective cohort)  whichever occurs first as
outlined in the Time and Events Schedule. Subjects who do not want to continue in the Follow-up

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Phase will be asked to complete and sign a withdrawal of consent form to specify if they agree to
have survival data collected or not. Assessments of survival status and alternate anticancer
therapies must be recorded in the eCRF. If necessary, this visit can occur by telephone.
9.2. 
Efficacy Evaluations
Disease assessments will be performed every 6 weeks for the first 6 months and then every
12 weeks for the next 6 months (±7-day window) using date of randomization as reference
(regardless of interruptions in treatment), as outlined in the Time and Events Schedule. After the
first year, assessments will be performed as clinically indicated. Assessment of responses for solid
tumors will be performed according to RECIST (Version 1.1) by investigators. For subjects who
discontinue study drug before disease progression, tumor assessments should continue as
described in Section 9.1.3.
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 (on the basis of global deterioration of health status) occurs without
documentation of radiographic progression, 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.
9.2.1. 
Evaluations
9.2.1.1. 
RECIST 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).
After screening, imaging will be repeated during the study as indicated in the Time and Events
Schedule.
9.2.1.2. 
Radiographic Images Assessment
Computed tomography (CT) scans of the chest, abdomen, pelvis, and any other location where
disease is present will be performed at Screening, and at each subsequent disease assessment visit.
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).
Brain MRI and lumbar puncture are required, only if clinically indicated.

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Imaging should not be delayed due to delays in cycle starts or extension of cycle intervals. After
disease progression is documented, subjects will have an End-of-Treatment Visit and continue in
the study for follow-up as outlined in Section 9.1.4.
9.2.2. 
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 or pembrolizumab may be continued at the discretion
of the investigator. Repeat tumor imaging at least 4 weeks after the first tumor imaging indicating
progressive disease. If repeat imaging still meets the threshold for PD (eg, ≥20% increase in tumor
burden compared to the nadir) but shows no clinically significant increase in tumor burden
compared to the previous time point, treatment may be continued as per treatment calendar after
consultation with the sponsor. If repeat imaging confirms progressive disease and clinically
significant increase in tumor burden compared to the previous time point, subjects will be
discontinued from study therapy.
9.3. 
Pharmacokinetics
Venous blood samples will be collected for determination of plasma concentrations of erdafitinib
and alpha-1-acid glycoproteins, total protein, and fraction unbound, if required, at the time points
specified in the Time and Events Schedule, for all subjects randomized to erdafitinib arms
(Arm 1A and Arm 2A). On PK sampling day C1D14, 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 post-dose sample should be collected during
the visit. On C2D1, the dose should be withheld; upon admission to the site, a PK sample (predose)
will be collected and the erdafitinib dose can then be taken. The safety ECG will be recorded at
approximately the time of maximal erdafitinib concentration (2-4 hour postdose, see Section 9.7.5)
and a second sample will be obtained after the ECG recording. The time of dosing and the time of
PK 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, unscheduled blood samples
may be collected. The total number of samples and blood volume will not be substantially
increased without approval of ethics committees/institutional review boards. The Laboratory
Manual provides further information regarding handling and shipment of blood/plasma samples.
9.3.1. 
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. AGP and other proteins will also
be measured. 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.
9.4. 
Predictive and Pharmacodynamic Biomarkers
Tissue will be collected in this study to determine both PD-(L)1 expression and the bladder cancer
subtype of enrolled subjects, and correlation of these factors with FGFR status (presence of
mutation or gene fusion) and response to erdafitinib, pembrolizumab, or chemotherapy.

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To further elucidate the erdafitinib mechanism of action, the impact of erdafitinib on peripheral
immune cells (and tumor immune cell infiltrate, where available) will be assessed. Erdafitinib was
observed to increase tumor T cell infiltrate and clonal expansion in a genetically engineered mouse
model of lung cancer harboring an FGFR2 mutation (unpublished data). Assessment of peripheral,
and tumor immune cell infiltrate in this study, will determine whether these preclinical
observations occur in subjects treated with erdafitinib, and whether changes in immune cell
number, profile or activation status correlate with clinical response to erdafitinib.
Germline DNA will be collected for subjects on erdafitinib (see Time and Events Schedule) from
a blood sample for the purpose of CYP2C9 genotyping to allow exploration of the effect of
CYP2C9 polymorphism on the PK of erdafitinib.
Serum phosphate levels will be monitored in subjects treated with erdafitinib as a marker of target
engagement. The Phase 1 Study 42756493EDI1001 demonstrated that phosphate levels are a
robust pharmacodynamic biomarker, and that achieving target increases in serum phosphate may
be associated with clinical response to erdafitinib.
Tissue for Immune Biomarkers and Molecular Subtyping
Tissue collected on study will be used to assess the immune marker status and identify the
molecular subtype of subject tumors. Changes in the tumor in response to treatment with
erdafitinib (or chemotherapy or pembrolizumab) will be assessed in subjects who provide optional
pre- and post-treatment biopsies.
Tissue collected at screening will be used to:
 
Assess the status of immune biomarkers, including but not limited to PD-L1 expression, via
IHC
 
Determine the molecular subtype of tumor samples by RNA sequencing analysis or alternate
method.
Initially tissue for PD-L1 expression and subtyping will be collected from all subjects
(FGFR-negative and FGFR-positive) during molecular eligibility testing. Once approximately
80 samples are received from FGFR aberration-negative subjects, collections will continue only
for enrolled subjects (FGFR aberration-positive) for the remainder of the study. At the time of
protocol development, it was estimated that approximately 80 samples are needed to inform PD-L1
expression and bladder cancer subtype in FGFR aberration-negative subjects (see Section 11.5).
The correlation of PD-L1 status and bladder molecular subtype with FGFR alteration status, and
response to erdafitinib, chemotherapy, and pembrolizumab, will be assessed.
Optional paired biopsies will be collected pre-treatment (any time during the full screening period
prior to dosing on Cycle 1 Day 1), on-treatment (on or within 2 weeks after Cycle 2 Day 1), and
at disease progression. To understand if erdafitinib has an impact on tumor immune cell profile,
pre- and post-treatment tissue samples will be stained by IHC for expression of immune cell
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Paired biopsies may also be utilized for bladder cancer subtype determination (via RNA
sequencing or alternate method) to examine if treatment with erdafitinib (or chemotherapy or
pembrolizumab) induces a change in gene expression related to bladder cancer molecular subtype.
Biopsies may also be screened for the presence of FGFR alterations and alterations in other genes
to track FGFR status over the course of treatment and explore mechanisms of acquired resistance
in response to treatment with erdafitinib (or chemotherapy or pembrolizumab). This may be
accomplished via next-generation sequencing or alternate method.
Circulating Biomarkers
Blood samples for circulating biomarker should be collected predose at timepoints specified in the
Time and Events Schedule. Collection of samples may cease or time points may be modified based
on emerging data.
Peripheral Immune Cell Profiling
Profiling of peripheral immune cells and determination of activation status will be performed in
blood samples collected on study, via flow cytometry. T cell and Treg enumeration and T cell
activation status will be assessed at certain sites. Profiling of additional immune cell types,
eg, natural killer cells (NK) and myeloid derived suppressor cells (MDSCs), may also be
performed in blood. RNA sequencing, Nanostring, or alternate methodology may also be applied,
where appropriate.
T cell receptor sequencing will be performed to assess changes in T cell receptor clonality induced
by treatment with erdafitinib (or chemotherapy or pembrolizumab).
Circulating Tumor DNA
Blood for analysis of circulating tumor DNA (ctDNA) will be collected at multiple time points on
study. Analysis of ctDNA offers the potential of a non-invasive method to identify subjects for
molecularly-based targeted therapies, and to follow the emergence of response or resistance to
treatment. Circulating tumor DNA are fragments of DNA shed in the bloodstream during cell
turnover. In cancer, a fraction of the circulating DNA is made up from DNA shed by tumor cells.
This ctDNA often harbors somatic alterations which are reflective of the original tumor. The aim
is to identify alterations in FGFR and other genes in blood as markers of response or resistance to
erdafitinib, and to determine whether blood could serve as a suitable alternative to tumor tissue for
detection of FGFR alterations.
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 will 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,
pembrolizumab, or chemotherapy.

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Additional biomarkers (DNA, RNA, and protein) relevant to cancer may also be assessed in blood
and tissue samples collected on study to better understand the disease and mechanisms of response
or resistance to the erdafitinib, pembrolizumab, or chemotherapy.
Adjustments in the timing of biomarker collections may be made during the study based on
emerging data, however the number or volume of biomarker sampling will not increase.
Biomarker analyses are dependent upon the availability of appropriate biomarker assays and
emerging data, and may be deferred if during or at the end of the study it becomes clear that the
analysis will have no scientific value, or there are not enough samples or 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.
9.5. 
Patient Reported Outcomes
Patients health-related quality of life, symptoms, functioning, and general well-being will be
captured using 3 PRO measures: the FACT-Bl, PGIS, and the EQ-5D-5L. The PRO measures will
be collected electronically, if feasible, according to the Time and Events Schedule, to understand
change over time and difference between treatment groups in each cohort. EQ-5D-5L will be
collected in the Follow-up Phase until start of subsequent anti-cancer therapy.
The FACT-Bl consists of 39 core items, with 5-point Likert response scales, covering 5 primary
domains: physical well-being, social/family well-being, emotional well-being, functional
well-being and bladder symptom subscale. The answer scales range from “Not at all” to “very
much”. The FACT-Bl will be used to support PRO hypothesis testing (see Section 11.6).
The PGIS is a single question regarding the patient report of disease severity: Considering all
aspects of your bladder cancer symptoms right now would you say your bladder 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 EQ-5D-5L is a generic measure of health status. 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)
(Herdman 2011). The scores for the 5 separate questions are categorical and are 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.

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9.6. 
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.
9.7. 
Safety Evaluations
This study will be monitored in accordance with the sponsor’s Pharmacovigilance Committee
procedures. Adverse event and serious adverse event data will be reviewed internally on an
ongoing basis to identify safety concerns by the study medical monitor. In addition, the sponsor’s
Safety Management Team (SMT) will review the safety data routinely and will investigate specific
safety queries. The SMT will review all serious adverse events.
Safety assessments will be based on medical review of adverse event reports and the results of
vital sign measurements, electrocardiograms (ECGs), physical examinations, clinical laboratory
tests, ECOG performance status, ophthalmologic examinations, and other safety evaluations at
specified time points as described in the Time and Events Schedule.
Any clinically significant abnormalities or toxicities persisting at the end of the study will be
followed by the investigator until resolution or until reaching a clinically stable endpoint. For
adverse events such as skin/nail and mucosal toxicity, upon subject consent, photographs may be
taken for assessment and monitoring of the toxicity.
9.7.1. 
Adverse Events
Adverse events will be reported by the subject (or, when appropriate, by a caregiver, surrogate, or
the subject's legally acceptable representative) from the time of a signed and dated Full-Study ICF
until 30 days after the last dose of study drug. The incidence of adverse events will be tabulated
and reviewed for potential significance and clinical importance. Adverse events will be graded
according to the NCI-CTCAE, Version 4.03. Adverse events will be followed by the investigator
as specified in Section 12, Adverse Event Reporting. During the LTE Phase (Attachment 8), only
serious adverse events will be reported to the Company safety repository, which will be conducted
as specified in Section 12.3.2 using the appropriate serious adverse event reporting method.

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9.7.2. 
Clinical Laboratory Tests
Blood samples for serum chemistry and hematology will be collected according to the Time and
Events Schedule. 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.
Laboratory test results completedon Cycle 1 Day 1 should be reviewed prior to dosing and subjects
should continue to meet eligibility requirements per the Inclusion/Exclusion criteria.
The following tests will be performed by the local laboratory:
Hematology Panel
-hemoglobin
-platelet count
-white blood cell (WBC) count and ANC only
Serum Chemistry Panel
-alanine aminotransferase (ALT) 
-potassium
-aspartate aminotransferase (AST) 
-sodium
-total bilirubin  
-magnesium
-chloride 
-alkaline phosphatase
-bicarbonate; only applicable if the test is
locally available
-creatinine
Serum phosphate, serum parathyroid hormone, calcium (or, if applicable, corrected calcium in the
case of hypoalbuminemia), and albumin will be tested for all subjects at screening.
For subjects in Arms 1A and 2A only:
 Serum phosphate, calcium (or, if applicable, corrected calcium in the case of
hypoalbuminemia), and albumin is required on C1D1, C1D14, C2D1, C2D14, C3D1, C3D14
and then from Cycle 4 onwards, only on Day 1 and at the EOT visit.
Serum parathyroid hormone is required on C1D1, C1D14, C2D1, C2D14, C3D1, C3D14, C4D1,
C5D1, C6D1 and then every third cycle thereafter on Day 1 and at the EOT visit.
Thyroid stimulating hormone and free thyroxine 4 will be tested for all subjects at screening, and
every other cycle from Cycle 2 for subjects in Arm 2B only.
9.7.3. 
Renal Toxicity Evaluation
Creatinine or creatinine clearance will be determined per institutional standard.

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9.7.4. 
Urine or Serum Beta-hCG Pregnancy Test
A urine or serum sample will be obtained for a pregnancy test (β-hCG) in sexually active female
subjects of child-bearing potential at screening within 7 days of the first dose and at
End-of-Treatment. Additional serum or urine pregnancy tests will be performed on Day 1 of every
cycle, to establish the absence of pregnancy at any time during the subject's participation in the
study.
9.7.5. 
Electrocardiogram
12-lead electrocardiograms (ECGs) will be performed at any time during the screening period.
Postdose ECGs for subjects in Arm 1A and Arm 2A should be recorded 2 to 4 hours after the
erdafitinib dose on Cycle 2 Day 1 and, if possible, 2 to 4 hours after the erdafitinib dose on Cycle 4
Day 1. Postdose ECGs for subjects in Arm 1B and Arm 2B should be recorded as soon as possible
upon completion of infusion on Cycle 2 Day 1 and 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. Triplicate ECGs should be performed with 5- to
10-minute intervals between each assessment. At least 1 printout of all 3 ECGs 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. The investigator will comment on the clinical relevance and document this in the eCRF
(along with details of clinically significant findings).
9.7.6. 
Ophthalmologic Examination
All subjects should 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) should also be performed at Screening. 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 central serous retinopathy (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 scans for enrolled subjects must be stored in the subject’s records and a
redacted copy sent to the sponsor-selected central vendor for possible future independent
assessment.

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Amsler grid (Attachment 4) testing will be administered to all subjects at Screening and during the
treatment phase only to subjects in Arm 1A and Arm 2A according to the Time and Events
Schedule. 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 exam within 7 days. However, if the subject has an abnormal
Amsler grid test and otherwise normal ophthalmologic exam at baseline 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.
9.7.7. 
Vital Signs
Blood pressure (systolic and diastolic), heart rate, and temperature will be assessed. Abnormalities
will be recorded as AEs.
9.7.8. 
Physical Examination
A full physical examination, including neurological examination, height, and weight will be
performed at screening. Subjects should have a repeated physical examination at Cycle 1 Day 1
prior to dosing if the previous one during screening occurred more than 7 days before first dosing.
Limited physical examinations of involved organs, neurological examination, and weight, will be
performed at subsequent visits as listed in the Time and Events Schedule. New abnormalities will
be recorded as AEs.
9.7.9. 
ECOG Performance Status
Eastern Cooperative Oncology Group (ECOG) performance status grade will be determined at pre-
specified time points listed in the Time and Events Schedule. Subjects should have a repeated
ECOG assessment at Cycle 1 Day 1 prior to dosing if the previous one during screening occurred
more than 7 days before first dosing. The scoring information is provided in Attachment 1.
9.8. 
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the laboratory requisition
form/source documentation. Refer to the Time and Events Schedules for the timing and frequency
of all sample collections. Instructions for the collection, handling, and shipment of samples are
found in the Laboratory Manual.
10. 
SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/
WITHDRAWAL FROM THE STUDY
10.1. Completion
A subject will be considered as having completed the study if he or she has died during the study
or has not been withdrawn by study completion (ie, at the end of data collection timepoint).

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10.2. Discontinuation of Study Treatment/Withdrawal From the Study
Discontinuation of Study Treatment
A subject who discontinues study treatment will continue to participate in the study for follow-up
of survival status, subsequent anti-cancer therapy, EQ-5D-5L completion, and resolution of any
ongoing drug-related AEs. For subjects who discontinue treatment before disease progression,
every effort should be made to continue to monitor their disease status according to the Time and
Events Schedule (see Section 9.1.3).
A subject's study treatment must be discontinued if:
 
The investigator believes that for safety reasons, tolerability reasons, or impairment of the
subject’s well-being (eg, due to AEs such as those described in Section 6) it is in the best
interest of the subject to discontinue study treatment
 
The subject experiences an AE that, as described in Section 6, should result in discontinuation
of 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 erdafitinib or pembrolizumab 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 treatment, an End-of-Treatment Visit should be conducted 30 (+7) days
of 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 eCRF. Once a subject
discontinues treatment with the study drug, the subject will not be permitted to be retreated.
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
If a subject is lost to follow-up, every reasonable effort must be made by the study-site personnel
to contact the subject and determine the reason for discontinuation/withdrawal. The measures
taken to follow up must be documented.

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When a subject withdraws consent before completing the study, the reason for withdrawal is to be
documented in the eCRF and in the source document. In addition, subjects who withdraw consent
must complete and sign a withdrawal of consent form to specify if they agree to have survival data
collected or not. Study drug assigned to the withdrawn subject may not be assigned to another
subject. Subjects may be replaced only if the subject withdrew prior to the study drug
administration.
10.3. Withdrawal from the Use of Research Samples
The subject may withdraw consent for use of samples for future research (refer to Section 16.2.5,
Long-Term Retention of Samples for Additional 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 Full-Study ICF.
11. 
STATISTICAL METHODS
Statistical analysis will be done 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.
11.1. Subject Information
The analysis populations are defined as:
1. Intent-to-Treat (ITT) population: defined as all randomized subjects. Subjects in this
population will be analyzed according to the treatment to which they are randomized.
2. Pharmacokinetic-evaluable population: defined as all randomized subjects who received at
least 1 dose of erdafitinib and had at least 1 evaluable pharmacokinetic sample obtained
posttreatment.
3. Biomarker population: defined as all randomized subjects with at least 1 biomaterial available
and who have consented to participate in the study’s biomarker evaluations.
4. Safety population: defined as all randomized subjects who received at least 1 dose of study
drug. Safety data will be analyzed according to the actual treatment received.
The ITT population will be used to summarize the study population and characteristics, efficacy,
PRO data, and health economic data; the safety population will be used to summarize the safety
data, unless otherwise specified.
11.2. Sample Size Determination
Cohort 1 will enroll approximately 280 subjects (approximately 140 subjects to each arm). The
data cutoff date for the final analysis will be when approximately 208 death events have occurred.
Assuming 53% improvement in median OS of the erdafitinib arm over the chemotherapy arm (a
hazard ratio [HR] of 0.65 for the erdafitinib relative to chemotherapy group, under the exponential
distribution assumption), the study has at least 85% power to detect a HR of 0.65 at a statistical
significance level of 5% (2-sided) with one interim analysis for efficacy at an approximately 65%
information fraction (approximately 136 deaths) and a final analysis.

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Cohort 2 will enroll approximately 350 subjects (approximately 175 subjects to each arm). The
data cutoff date for the final analysis will be when approximately 264 death events have occurred.
Assuming 46% improvement in median OS of the erdafitinib arm over the pembrolizumab arm (a
hazard ratio of 0.69 for the erdafitinib relative to the pembrolizumab group, under the exponential
distribution assumption), the study has at least 85% power to detect an HR of 0.69 at a statistical
significance level of 5% (2-sided) with one interim analysis for efficacy at an approximately 65%
information fraction (approximately 172 deaths) and a final analysis.
The randomization for both cohorts is stratified by the following factors: region (North America
vs EU vs rest of world), Eastern Cooperative Oncology Group (ECOG) performance status (0 or
1 vs. 2) and the presence of visceral metastases (yes, no).
11.3. Efficacy Analyses
Descriptive statistics and subject listings will be used to summarize the data. For continuous
variables, number of observations, means, standard deviations, medians, quartiles, and ranges will
be used. For discrete variables, frequency will be summarized. For time-to-event variables,
Kaplan-Meier (KM) estimates will be provided, and a stratified log-rank test will be used. The
type 1 error will be controlled at 5% (2-sided) only within each cohort. All tests will be conducted
at a 2-sided alpha level of 0.05, and 95% confidence intervals (CI) will be provided, unless stated
otherwise. Each cohort will be analyzed separately.
11.3.1. 
Primary Endpoint
The primary endpoint is OS. The primary efficacy analysis will be based on the ITT population
that includes all randomized subjects in each cohort. The Kaplan-Meier method will be used to
estimate the distribution of OS for each treatment group within each cohort. The stratified log-rank
test will be used to compare survival curves of OS between the 2 treatment arms. The stratification
factors to be used in the analysis are as follows: region (North America vs EU vs rest of world),
ECOG performance status (0 or 1 vs 2), and disease distribution (presence vs absence of visceral
metastases: lung, liver, or bone). Pre-specified strata combining will be implemented when some
strata have too few OS events, as specified in the SAP.
Additionally, the hazard ratio for erdafitinib relative to the control and its associated 95% CI will
be calculated based on the Cox proportional hazards model.
11.3.2. 
Secondary Efficacy Endpoints
The secondary efficacy endpoints are listed in Section 2.1.2. PFS will be analyzed the same as OS.
Kaplan-Meier method will be used to estimate the distribution of DOR. ORR will be analyzed by
Cochran-Mantel-Haenszel chi-square test for randomized subjects with measurable disease at
baseline. The analyses of the secondary efficacy endpoints will include all randomized subjects
(ITT subjects) unless otherwise specified. The family-wise type 1 error will be strongly controlled
at 5% (2-sided) for the secondary efficacy endpoints. Specific details will be provided in the SAP.

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11.3.3. 
Subgroup Analyses
The primary efficacy and secondary efficacy endpoints will be analyzed by each subgroup. A list
of subgroups and their definitions will be described in the SAP.
11.3.4. 
Baseline Assessments
All demographic and baseline characteristics will be summarized for the ITT population. The
baseline value is defined as the value collected at the time closest to but prior to the randomization.
11.4. Pharmacokinetic and Pharmacokinetic/Pharmacodynamic Analyses
Pharmacokinetic data will be listed for all subjects with available plasma concentrations. 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, efficacy or
treatment-emergent adverse events may also be explored as data allow using population
approaches. Results of the analyses will be provided in a separate report.
11.5. Biomarker Analyses
PD-L1 high rate by immunohistochemistry in FGFR alteration-negative, molecular-screening non-
qualified subjects, will be compared with PD-L1 high rate in FGFR alteration-positive subjects.
At least 80 FGFR alteration-negative subjects will be tested for PD-L1 status in tumor tissue. All
enrolled FGFR alteration-positive subjects will be tested for PD-L1 status. Assuming the PD-L1
high rate in FGFR alteration-negative subjects is 40% and the PD-L1 high rate in FGFR alteration-
positive subjects is 15%, the estimated sample size will have at least 80% power to achieve a
statistical significance level of 5% (2-sided).
Within each cohort, approximately 45 subjects in the erdafitinib arm and approximately
15 subjects in the comparator arm (a total of 60 subjects per cohort) represent the minimum number
of subjects whose samples are anticipated to be tested via flow cytometry and TCR sequencing.
Samples from approximately 45 subjects in the erdafitinib arm will produce a 2-sided 90% CI with
a width equal to 0.25 when 50% of subjects in each erdafitinib arm achieve at least 20% relative
change from baseline to post-baseline. Sample collections will continue until at least 45 subjects
are enrolled in the erdafitinib arm of each cohort to support these analyses, or until collections are
no longer needed, as data warrant.
Blood for ctDNA analysis will be collected from all subjects on study. Sample size calculations
were performed to determine how many samples needed to be tested in order to observe the
emergence of markers of resistance to erdafitinib treatment. For subjects treated with erdafitinib,

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samples from approximately 145 subjects among responders and approximately 145 subjects
among non-responders will be assayed by next-generation sequencing of ctDNA. This sample size
produces a 2-sided 95% CI with a width equal to 0.15 when the acquired resistance (among
responders) and intrinsic resistance (among non-responders) proportion in each group is 0.30.
Samples not tested and samples collected from the comparator arms will be stored for future
investigation into the mechanisms of resistance and comparison with prior findings.
For each of the biomarker samples sizes estimated above, the number of subjects for which samples
are collected may be modified based on emerging data. Collections may continue, stop, or time
points modified based on emerging data.
Results of exploratory pharmacodynamic 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.
Changes in molecular markers (FGFR or other genes), bladder cancer subtype markers, immune
cells or markers, and phosphate 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.
11.6. Medical Resource Utilization and Patient Reported Outcomes Analyses
Medical resource utilization and Patient-reported Outcomes will be summarized descriptively by
treatment group. Additional analyses may be conducted; details and results of any additional
analyses will be presented in a separate report.
The hypothesis is that patient reported time to urinary symptom deterioration will be delayed as
measured by relevant items in the FACT-Bl. Further, time to meaningful functional deterioration
will be significantly longer as measured by the Physical Well-being Scale (FACT-Bl).
11.7. 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 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 treatment group. In addition, comparisons
between treatment groups will be provided if appropriate.
Summaries, listings, datasets, or subject narratives may be provided, as appropriate, for those
subjects who die, who discontinue treatment due to an adverse event, or who experience a severe
or a serious adverse event.

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Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test. Reference ranges and markedly
abnormal results (specified in the SAP) 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 posttreatment 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.
Electrocardiograms
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) (ICH E14 2005).
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.
ECOG PS
ECOG scores 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.

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11.8. Interim Analysis
There is one planned interim analysis for each cohort. The interim analyses are planned after an
approximately 65% information fraction (approximately 136 of 208 deaths) in Cohort 1 and
(approximately 172 of 264 deaths) in Cohort 2 will have occurred. Both superiority and futility
will be assessed for Cohort 1 and Cohort 2. The classical O’Brien-Fleming boundaries will be used
for these assessments. The stopping boundaries will be implemented by Lan-DeMets spending
function to control the Type 1 error at the 0.05 significance level overall for each cohort. The
futility assessment for each cohort is not binding. Also, each cohort may be stopped when the HR
is 1.0 or greater, taking into consideration the totality of the data. Specific details will be provided
in the interim analysis plan (IAP).
Procedures will be in place to ensure that the results of the interim analysis do not influence the
conduct of the study, investigators, or subjects.
11.9. Independent Data Monitoring Committee
An Independent Data Monitoring Committee (IDMC) will be commissioned for reviewing safety
and efficacy data from this study. For each cohort, a review of the safety data will be performed
after at least 60 subjects have been enrolled in that cohort and every 6 months thereafter. The
IDMC will review the interim efficacy and safety analysis results for each cohort and will make
recommendations regarding study continuation based on the pre-specified boundary and the
guidance on futility as outlined in the IAP. The IDMC will consist of at least three medical experts
in the relevant therapeutic area and at least one statistician. The details will be provided in a
separate IDMC charter.
12. 
ADVERSE EVENT REPORTING
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.
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.
Solicited Adverse Events
Solicited adverse events are predefined local and systemic events for which the subject is
specifically questioned.

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Unsolicited Adverse Events
Unsolicited adverse events are all adverse events for which the subject is specifically not
questioned.
12.1. Definitions
12.1.1. 
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 noninvestigational) product. An adverse event does not necessarily
have a causal relationship with the treatment. 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 -noninvestigational) product, whether or not related
to that medicinal (investigational or -noninvestigational) product. (Definition per International
Council for Harmonisation [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
Section 12.3.1, All Adverse Events, 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
 
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.

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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 Investigator's Brochure. For vinflunine, docetaxel,
and pembrolizumab, the expectedness of an adverse event will be determined by whether or not it
is listed in the corresponding package insert/summary of product characteristics.
Adverse Event Associated with the Use of the Drug
An adverse event is considered associated with the use of the drug if the attribution is possible,
probable, or very likely by the definitions listed in Section 12.1.2, Attribution Definitions.
12.1.2. 
Attribution Definitions
Not Related
An adverse event that is not related to the use of the drug.
Doubtful
An adverse event for which an alternative explanation is more likely, eg, concomitant drug(s),
concomitant disease(s), or the relationship in time suggests that a causal relationship is unlikely.
Possible
An adverse event that might be due to the use of the drug. An alternative explanation,
eg, concomitant drug(s), concomitant disease(s), is inconclusive. The relationship in time is
reasonable; therefore, the causal relationship cannot be excluded.
Probable
An adverse event that might be due to the use of the drug. The relationship in time is suggestive
(eg, confirmed by dechallenge). An alternative explanation is less likely, eg, concomitant drug(s),
concomitant disease(s).
Very Likely
An adverse event that is listed as a possible adverse reaction and cannot be reasonably explained
by an alternative explanation, eg, concomitant drug(s), concomitant disease(s). The relationship in
time is very suggestive (eg, it is confirmed by dechallenge and rechallenge).
12.1.3. 
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 4.03. Any adverse event or serious adverse event not listed in the NCI-CTCAE,
Version 4.03 will be graded according to the investigator clinical judgment by using the standard
grades as follows:

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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.
 
Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization
or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily
living.
 
Grade 4: Life-threatening consequences; urgent intervention indicated.
 
Grade 5: Death related to adverse event.
The investigator should use clinical judgment in assessing the severity of events not directly
experienced by the subject (eg, laboratory abnormalities).
12.2. Special Reporting Situations
Safety events of interest on a sponsor study drug 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.
12.3. Procedures
12.3.1. 
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 (no adverse events will be collected for subjects
signing the molecular ICF only) is obtained until 30 days after last dose of study drug. Subjects
who discontinue study drug due to drug-related toxicity will continue to be monitored for this
toxicity until the toxicity resolves to baseline, stabilizes, or is deemed irreversible, the subject dies,
or subsequent therapy is started, whichever occurs first. 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.
Adverse events that occur between signing the ICF for assessment of molecular eligibility and
before signing the full study eligibility screening ICF will not be collected.

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All events that meet the definition of a serious adverse event will be reported as serious adverse
events, regardless of whether they are protocol-specific assessments. Anticipated events will be
recorded and reported as described in Attachment 6. Some countries/territories require reporting
of all adverse events to health authorities, eg, Japan will not identify anticipated events for the
health authorities.
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.
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). For
anticipated events reported as individual serious adverse events the sponsor will make a
determination of relatedness in addition to and independent of the investigator’s assessment. The
sponsor will periodically evaluate the accumulating data and, when there is sufficient evidence
and the sponsor has determined there is a reasonable possibility that the drug caused a serious
anticipated event, they will submit a safety report in narrative format to the investigators (and the
head of the investigational institute where required). 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.
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 staff only)
 
Site number
 
Subject number
12.3.2. 
Serious Adverse Events
All serious adverse events occurring during the study must be reported to the appropriate sponsor
contact person by study-site personnel within 24 hours of their knowledge of the event.

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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).
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
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.

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12.3.3. 
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 should be withdrawn from the study after consultation with the
sponsor’s medical monitor.
Because the effect of the study drug on sperm is unknown, pregnancies in partners of male subjects
included in the study will be reported as noted above.
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.
12.3.4. 
Disease-related Events and Disease-related Outcomes Not Qualifying
as Adverse Events or Serious Adverse Events
All events that meet the definition of a serious adverse event will be reported as serious adverse
events, regardless of whether they are protocol-specific assessments.
Progression of disease should not be considered nor should be reported an AE (or serious adverse
event). However, signs and symptoms of disease progression or of clinical sequelae resulting from
disease progression/lack of efficacy that are determined by the investigator to be of clinical
significance should be reported per the usual reporting requirements (see Section 12 Adverse
Event Reporting).
12.4. 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.
13. 
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.

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13.1. 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 12.3.2, Serious Adverse Events). A sample of the suspected product should be maintained
for further investigation if requested by the sponsor.
13.2. 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.
14. 
STUDY DRUG INFORMATION
14.1. Physical Description of Study Drug(s)
Erdafitinib will be supplied as 3-mg, 4-mg, and 5-mg tablets for oral use. Refer to the Investigator’s
Brochure for a list of excipients.
Vinflunine 250 mg (25 mg/mL) will be provided by the sponsor.
Docetaxel 80 mg (20 mg/mL) will be provided by the sponsor.
Pembrolizumab 100 mg (25 mg/mL) will be provided by the sponsor.
14.2. Packaging
Erdafitinib tablets for oral use in this study will be packaged in child-resistant packaging bottles.
Each bottle will contain 30 tablets/bottle for each strength: 3 mg, 4 mg, and 5 mg
Vinflunine 250 mg (25 mg/mL) will be packaged as 1 vial in a non-resistant carton.
Docetaxel 80 mg (20 mg/mL) will be packaged as 1 vial in a non-resistant carton.
Pembrolizumab 100 mg (25 mg/mL) will be packaged as 1 vial in a non-resistant carton.
14.3. Labeling
The study drugs must be stored in a secure area and administered only to subjects entered into the
clinical study in accordance with the conditions specified in this protocol. Study-site personnel
will instruct subjects on how to store study drugs for at-home use as indicated for this protocol.
Subjects should be advised to keep all medications out of reach and sight of children.
Study drug labels will contain information to meet the applicable regulatory requirements.

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14.4. Preparation, Handling, and Storage
Refer to the pharmacy manual/study site investigational product and procedures manual for
additional guidance on study drug preparation, handling, and storage.
14.5. Drug Accountability
The investigator is responsible for ensuring that all study drug received at the site is inventoried
and accounted for throughout the study. For erdafitinib, the dispensing of study drug to the subject,
and the return of study drug from the subject (if applicable), must be documented on the drug
accountability form. Subjects, or their legally acceptable representatives where applicable, must
be instructed to return all original containers, whether empty or containing study drug. For
vinflunine, docetaxel, and pembrolizumab, the study drug administered to the subject must be
documented on the drug accountability form. 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 the 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 drug 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 drug 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 drug accountability purposes.
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.
15. 
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following supplies:
 
Erdafitinib Investigator's Brochure
 
Vinflunine SmPC
 
Docetaxel Package Insert or SmPC
 
Pembrolizumab Package Insert

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Pharmacy manual/study site investigational product and procedures manual
 
Laboratory manual
 
NCI-CTCAE Version 4.03
 
PRO completion guidelines
 
RECIST guidelines Version 1.1
 
IVRS/IWRS Manual
 
eDC Manual
 
eSource Manual
 
Sample ICF
16. 
ETHICAL ASPECTS
16.1. Study-Specific Design Considerations
This is a Phase 3, multicenter, open-label randomized study to evaluate the efficacy and safety of
erdafitinib, an oral pan-FGFR-inhibitor with pharmacodynamic adaptation of dose (starting dose
of 8 mg once daily with potential up-titration to 9 mg once daily based on observed phosphate
level on Study Day 14) compared to vinflunine, docetaxel or pembrolizumab in subjects with
metastatic or surgically unresectable urothelial cancer with select FGFR genetic alterations who
have progressed on or after 1 or 2 prior treatments, at least 1 of which includes an anti-PD-(L)1
agent (Cohort 1) or 1 prior treatment not containing an anti-PD-(L)1 agent (Cohort 2).
The collective experience from both the Phase 1 and current ongoing global Phase 2 trials, suggest
that the proposed regimen is likely to be well tolerated. Objective tumor response is reported with
erdafitinib in this specific population; with ORR of 70.0% (7/10 subjects) for response-evaluable
subjects with urothelial cancer in the 9 mg once daily regimen in the Study EDI1001 and ORR of
39.7%, including confirmed and unconfirmed CR and PR, in the 8 mg once daily regimen in Study
BLC2001. For subjects in the 8 mg once daily group whose dose was increased to 9 mg, ORR was
50.0%.
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 who are fully able to understand the risks, benefits, and
potential adverse events of the study, and provide their consent voluntarily will be enrolled.
All participating subjects will receive full supportive care and will be followed closely for safety
and efficacy throughout the trial, as outlined in the Time and Events Schedules.
The total blood volume to be collected is considered to be within the normal range allowed for this
adult subject population over this time frame (North Shore LIJ 2014).

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16.2. Regulatory Ethics Compliance
16.2.1. 
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current ICH guidelines on Good Clinical Practice (GCP), and applicable regulatory and
country- or /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.
16.2.2. 
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)
 
Investigator's Brochure (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

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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, if applicable
 
New edition(s) of the Investigator's 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
 
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 (if applicable, the notification will be submitted through the head of
investigational institution).
16.2.3. 
Informed Consent
Each subject (or a legally acceptable representative) must give written consent according to local
requirements indicating that he or she understands the nature, significance, purpose of, procedures
for, and consequences of the study and is willing to participate in the study. The ICF(s) must be
signed before performance of any study-related activity. The ICF(s) 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.
Informed consent for molecular eligibility may be obtained remotely.
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

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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 treating 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
all written information) and should personally date and sign the ICF after the oral consent of the
subject [or legally acceptable representative is obtained.
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.
16.2.4. 
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 explicit consent for the processing of personal data and for the investigator/institution to

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allow direct access to his or her original medical records (source data/documents) for study-related
monitoring, audit, IEC/IRB review, and regulatory inspection. This consent also addresses the
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. Reasonable 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.
Exploratory PD, 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.
16.2.5. 
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, vinflunine, docetaxel,
or pembrolizumab, to understand urothelial cancer, to understand differential drug responders, and
to develop tests/assays related to erdafitinib, vinflunine, docetaxel, or pembrolizumab, and
urothelial cancer. 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 10.3, Withdrawal From the Use of Samples in Future Research.
16.2.6. 
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 16.1, Study-Specific Design
Considerations.
17. 
ADMINISTRATIVE REQUIREMENTS
17.1. 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

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change(s) involves 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
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.
17.2. Regulatory Documentation
17.2.1. 
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.
17.2.2. 
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

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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
 
Local laboratory documentation demonstrating competence and test reliability
(eg, accreditation/license), if applicable
17.3. 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 date of birth. In cases where the subject is not randomized into the study, the date seen and
date of birth will be used.
The investigator must also complete a subject screening log, which reports on all subjects who
were seen to determine eligibility for inclusion in the study.
17.4. Source Documentation
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;
drug 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 4.1 and Section 4.2 that specify a need for documented medical history are as follows:

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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 electronic source 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 the electronic source system is utilized, references made to the
CRF in the protocol include the electronic source system but information collected through the
electronic source system may not be limited to that found in the CRF. Data in this system may be
considered source documentation.
17.5. Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each subject in electronic format.
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 subjective measurements (eg, pain scale information or other questionnaires) will be completed
by the same individual who made the initial baseline determinations whenever possible.
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.
17.6. 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

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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.
17.7. 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.
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.
17.8. 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

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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.
17.9. Study Completion/Termination
17.9.1. 
Study Completion (ie, End of Data Collection Timepoint) and End of
Study
Study Completion (ie, End of Data Collection Timepoint)
The study is considered completed at the time of the end-of-data-collection timepoint for both
study cohorts. The-end-of-data-collection timepoint is defined as when the clinical cutoff at
final analysis has been achieved. At that time, participation in the Follow-Up Phase and will
end and the data collection will conclude. (For Cohort 1, the Sponsor will notify the
investigators if the interim analysis will be considered the final analysis.)
The subject completion definition is provided in Section 10.1
End of Study
The end of study is defined as when the last subject receives the last dose of study drug on the
study.
17.9.2. 
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, eg in case of unacceptable risk, intolerable toxicity, or
change in the risk/benefit profile; this might include recurrence of adverse events of which
character, severity, or frequency is new in comparison to the existing risk profile. Data derived
from other clinical trials or toxicology studies which negatively influence the risk/benefit
assessment might cause discontinuation or termination of the study. 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.

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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
17.10. 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 he or she has
been contacted by a regulatory agency concerning an upcoming inspection.
17.11. Use of Information and Publication
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
previously published, and any data, including exploratory 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. Results of exploratory 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

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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 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 substudy 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 12 months of the availability of the final data (tables, listings,
graphs), 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 Uniform Requirements for Manuscripts Submitted to Biomedical Journals, which
state that the named authors must have made a significant contribution to the design of the study
or analysis and interpretation of the data, provided critical review of the paper, and given final
approval of the final version.
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.

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REFERENCES
Bajorin DF (1999), Dodd PM, Mazumdar M, et al. Long-term survival in metastatic transitional-cell carcinoma and
prognostic factors predicting outcome of therapy. J Clin Oncol. 1999;17(10):3173–3181.
Bellmunt J (2014), Orsola A, Leow JJ, et al on behalf of the ESMO Guidelines Working Group. ESMO Guidelines:
Bladder cancer: ESMO Practice Guidelines for Diagnosis, Treatment, and Follow-up. Annals of Oncology.
2014;25(suppl 3):iii40-iii48.
Bellmunt J (2009), Theodore C, Demkov T, et al. Phase III trial of vinflunine plus best supportive care compared with
best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma
of the urothelial tract. J Clin Oncol. 2009;27(27):4454-4461.
Choi W (2017), Ochoa A, McConkey DJ, et al. Genetic alterations in the molecular subtypes of bladder cancer:
Illustration in the Cancer Genome Atlas Dataset. Eur Urol. 2017;72(3):354-365.
Choi W (2014), Porten S, Kim S, et al. Identification of distinct basal and luminal subtypes of muscle-invasive bladder
cancer with different sensitivities to frontline chemotherapy. Cancer Cell. 2014;25(2):152-165.
Damrauer JS (2014), Hoadley KA, Chism DD, et al. Intrinsic subtypes of high-grade bladder cancer reflect the
hallmarks of breast cancer biology. Proc Natl Acad Sci USA. 2014;111(8):3110-3115.
Davarpanah NN (2017), Yuno A, Trepel JB, Apolo AB. Immunotherapy: a new treatment paradigm in bladder cancer.
Curr Opin Oncol. 2017;29(3):184-195. doi: 10.1097/CCO.0000000000000366.
Ferlay J (2013), Steliarova-Foucher E, Loret-Tieulent J, et al. Cancer incidence and mortality patterns in Europe:
estimates for 40 countries in 2012. Eur J Cancer. 2013;49:1374.
Herdman M (2011), 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.
Howlader N (2016), Noone AM, Krapcho M, et al (eds). SEER Cancer Statistics Review, 1975-2014, National Cancer
Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975 2014/, based on November 2016 SEER data submission,
posted to the SEER web site, April 2017.
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human
Use (2015). ICH Harmonized Tripartite Guideline E14: Clinical evaluation of QT/QTc interval prolongation and
proarrhythmic potential for non-antiarrhythmic drugs. ICH 12 May 2005.
Karajannis MA (2006), Vincent L, Direnzo R, et al. Activation of FGFR1beta signaling pathway promotes survival,
migration and resistance to chemotherapy in acute myeloid leukemia cells. Leukemia. 2006;20(6):979-986.
Lerner SP (2017), Robertson G, Kim J, et al. Comprehensive molecular characterization and analysis of muscle-
invasive urothelial carcinomas. J Clin Oncol. 2017;35(15 suppl):4500-4500.
McCaffrey JA (1997), Hilton S, Mazumdar M, et al. Phase II Trial of Docetaxel in Patients with Advanced or
Metastatic Transitional-Cell Carcinoma. J Clin Oncol. 1997;15:1853-1857.
Miller L (2017). The rapid uptake of immunotherapy in bladder cancer. Targeted Oncology June 16, 2017.
http://www.targetedonc.com/publications/targeted-therapy-news/2017/june-2017/the-rapid-uptake-of-
immunotherapy-in-bladder-cancer.
National Comprehensive Cancer Network (NCCN) Guidelines, Bladder Cancer Version 2.2017.
North Shore LIJ. Human subject protection program guidance document: Maximum blood draw limits.
2013.Available 
at: 
http://www.feinsteininstitute.org/wp-content/uploads/2013/02/Maximum-Blood-Draw-
Limits.pdf. Accessed on 31 October 2014.
Roidl A (2009), Berger HJ, Kumar S, et al. Resistance to chemotherapy is associated with fibroblast growth factor
receptor 4 up-regulation. Clin Cancer Res. 2009;15(6):2058-2066.
Rosenberg JE (2016), Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and
metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a
single-arm, multicentre, phase 2 trial. Lancet. 2016;387(10031):1909-1920.

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Seiler R (2017), Ashab HA, Erho N, et al. Impact of molecular subtypes in muscle-invasive bladder cancer on
predicting response and survival after neoadjuvant chemotherapy. Eur Urol. 2017; pii: S0302-2838(17)30251-8. doi:
10.1016/j.eururo.2017.03.030.
Sharma P (2017), Retz M, Siefer-Radke A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy
(CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017;18(3):312-322.
The Cancer Genome Atlas (TCGA) Research (2014). Comprehensive molecular characterization of urothelial bladder
carcinoma. Nature. 2014;507(7492):315-322.
Yafi FA (2011), North S, Kassouf W. First- and second-line therapy for metastatic urothelial carcinoma of the bladder.
Current Oncology. 2011;18(1):e25-e34.

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Attachment 1: ECOG Performance Status
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.

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Attachment 2: Cockcroft-Gault Formula for Estimated Creatinine Clearance
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
lhttp://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation/

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Attachment 3: 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.
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.

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Attachment 4: Amsler Grid

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Attachment 5: 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 
erythromycin
saquinavir 
troleandomycin
telaprevir
telithromycin
voriconazole
fluconazole
Strong Inhibitors: ≥5 fold increase in AUC or ≥80% decrease in clearance.
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.htm#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.

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Attachment 6: Anticipated Events
Purpose
This appendix applies only to the reporting of anticipated events by the Sponsor to the US FDA, and US-
based Investigators and IECs/IRBs, in accordance with the FDA’s guidance. The intent is to minimize the
submission of a multitude of uninformative IND safety reports to these recipients.
Definition of an Anticipated Event
An anticipated event is an AE (serious or non-serious) that commonly occurs, independent of exposure to
study treatment, as a consequence of (a) the underlying disease or condition under investigation, (b)
characteristics of the study population (eg, age), or (c) the background treatment regimen.
Background
The FDA acknowledges that certain serious adverse events can be anticipated to occur commonly in the
study population regardless of drug exposure. Although these anticipated serious adverse events may meet
the definition of unexpected (ie, SUSARs), because they are not listed in the IB, they do not warrant
expedited reporting as individual cases, or even in aggregate if the incidence is consistent with the expected
background rates in the study population.
For the purposes of this study the following events will be considered anticipated events:
cauda equina syndrome
haematuria
urinary incontinence
lymphedema
pathological fracture
spinal cord compression
urinary hesitation
ureteric obstruction
hydronephrosis
urine flow decreased, including oliguria
urinary retention
urinary tract obstruction
urinary tract stoma complication
urinary tract pain
urinary tract infection
urosepsis
Reporting of Anticipated Events
All adverse events will be recorded in the CRF regardless of whether considered to be anticipated events
and will be reported to the sponsor as described in Section 12.3.1, All Adverse Events. Any anticipated
event that meets serious adverse event criteria will be reported to the sponsor as described in Section 12.3.2,
Serious Adverse Events.
To meet US safety reporting, the Sponsor’s Safety Assessment Committee (SAC) will periodically perform
aggregate analysis of anticipated events per the Anticipated Events Safety Monitoring Plan (ASMP) (see
below). If an anticipated event is determined to occur more frequently in the experimental arm(s) of the
study and there is a reasonable possibility that the anticipated event could be drug-related, the Sponsor will
prepare an aggregate safety report for reporting of these events to FDA and US-based IRBs/ECs and
Investigators.

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Sponsor’s Safety Assessment Committee (SAC)
The Sponsor’s SAC is an established safety committee, independent of the study team, that performs
reviews of prespecified anticipated events at an aggregate level. The SAC will meet to aid in the
recommendation to the Sponsor’s study team as to whether there is a reasonable possibility that an
anticipated event is related to the study treatment. The SAC will consider in its analysis all relevant drug
development data, in addition to the clinical study data.
Statistical Analysis
Details of statistical analysis of anticipated events, including the frequency of review and threshold to
trigger an aggregate analysis of anticipated events will be provided in a separate Anticipated Events Safety
Monitoring Plan (ASMP).

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Attachment 7: Guidance on Study Conduct for Enrolled Subjects During a National Disaster
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 subject 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 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.

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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.

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Attachment 8: Long-Term Extension Phase with Potential Cross-over to Erdafitinib
The purpose of the Long-term Extension (LTE) Phase is to provide continued study drug to
subjects, while minimizing data collection burden. Subjects in the respective cohort 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 6.4). As an alternative
to entering the LTE Phase, subjects may exit the study and continue to receive treatment on any
other post-trial access program, when permitted by local regulations. (Also, potential cross-over
to erdafitinib treatment is discussed below under “Study Treatment Administration”.)
The LTE Phase for a given cohort begins with the approval of Amendment 6 and with achievement
of the final analysis for that cohort. (For Cohort 1, the Sponsor will notify the investigators if the
interim analysis will be considered the final analysis.)
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 (when study drug will be
supplied by the Sponsor after the data collection timepoint), only serious adverse events will be
reported to the Company safety repository, which will be conducted as specified in Section 12.3.2
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.
Criteria to Cross-over to Erdafitinib
Subjects entering the LTE Phase will continue to receive the study drug that they were receiving
at the time of transition to LTE. However, the Sponsor may decide to allow cross-over to
erdafitinib if superiority for erdafitinib for the primary objective of the respective cohort is
achieved and based on the IDMC recommendations. Subjects are eligible to cross-over to
erdafitinib up to 90 days after notification of cross-over. Subjects must meet the following criteria
to be eligible to cross-over to erdafitinib:
1. Subjects are willing and able to provide written informed consent to cross-over to erdafitinib.
2. Phosphate level must be less than ULN within 14 days prior to the cross-over (medical
management allowed)
3. No central serous retinopathy (CSR) or retinal pigment epithelial detachment.
4.  Subjects must have received comparator drug in the study within 60 days prior to notification
of cross-over.
5. Subjects must have progressed on or within 60 days after discontinuing comparator drug on
the study. Alternatively, cross-over to erdafitinib may be permitted if assessed to be in the
best interest of the subject due to suboptimal response to or toxicity of comparator therapy.
6. Subjects have not received any systemic anti-cancer therapy since discontinuing comparator
drug in the study.
Additional criteria may be required by the Sponsor based on the IDMC recommendation.
Subjects who elect not to continue in the LTE Phase will be discontinued from the study within
approximately 3 months from the initiation of the LTE Phase at the site.

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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 conduct of the study and the obligations of confidentiality.
Coordinating Investigator:
Name (typed or printed):
Institution and Address:
Signature: 
Date:
(Day Month Year)
Principal Participating Physician:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature: 
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer (Main Author):
Name (typed or printed): 
Institution: 
Janssen Research and 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 course of the study,
written notification will be provided by the investigator to the sponsor; a protocol amendment will not be
required.
PPD

Signature
User 
Date 
Reason
 
23-Jan-2023
14:21:45
(GMT)
Document Approval
PPD